尼帕病毒免疫原及其用途

相关申请的交叉引用

本申请要求于2018年8月3日提交的美国临时申请号62/714,230的优先权，其通过引用以其全文并入本文。

技术领域

本公开涉及用于引起和检测对尼帕病毒(Nipah virus，NiV)的免疫应答的多肽、多核苷酸、组合物及其使用方法。

背景技术

NiV是副粘病毒科(Paramyxoviridae)的有包膜的非节段负链RNA病毒。天然的NiV宿主是狐蝠科(Pteropodidae Family)的果蝠。从无症状感染到急性呼吸道综合征和致命性脑炎，人类NiV感染具有一系列临床表现。约四分之一的人类患者患有癫痫和约60％昏迷，并可能需要机械通气。NiV还能够引起猪和其他家畜疾病。

NiV病毒包膜包含几种膜蛋白，包括包膜蛋白F和附着蛋白G。NiV G蛋白是II型膜蛋白，可促进NiV附着在宿主细胞膜上。NiV F蛋白是与宿主细胞受体结合并促进宿主膜和病毒膜融合的I型膜蛋白。NiV F是I类融合蛋白，最初表达为单一多肽前体，称为F

尽管已知NiV可导致人类疾病和疾病负担，但尚无针对该病毒的疫苗。

发明内容

本文公开了重组NiV F胞外域三聚体，其包括原聚体，该原聚体包括使F胞外域三聚体以其融合前构象稳定的一个或更多个修饰(诸如氨基酸取代)。与未以融合前构象稳定的相应的NiV F胞外域三聚体相比，在动物模型中证明了这种融合前稳定的NiV F胞外域三聚体的实施方式可产生优异的免疫应答。

在一些实施方式中，重组NiV F胞外域三聚体包括原聚体，所述原聚体包括将NiVF胞外域三聚体稳定在融合前构象的一个或更多个氨基酸取代，其中所述一个或更多个氨基酸取代包括以下一个或更多个：形成非天然原聚体内二硫键的NiV F 104位和114位的半胱氨酸取代(诸如L104C和I114C取代)或形成非天然原聚体内二硫键的NiV F 114位和426位的半胱氨酸取代(诸如I114C和I426C取代)、NiV F 191位的脯氨酸取代(诸如S191P取代)、NiV F 172位的苯丙氨酸取代(诸如L172F取代)、NiV F 70位的甘氨酸取代(诸如Q70G取代)，以及NiV F 102-113位的缺失，其中101位和114位通过甘氨酸-丝氨酸接头连接(诸如(HDLVGDVRLAGV)102-113(GSG)取代)。在非限制性实施方式中，所述一个或更多个氨基酸取代包括形成非天然原聚体内二硫键的NiV F 104位和114位的半胱氨酸取代、NiV F 191位的脯氨酸取代和NiV F 172位的苯丙氨酸取代。

在一些实施方式中，重组NiV F胞外域三聚体的原聚体的C端残基(诸如三聚体茎区的残基)与三聚结构域(诸如GCN4三聚结构域或T4纤维蛋白三聚结构域)相连，以促胞外域三聚化。在一些实施方式中，免疫原可溶。在其他实施方式中，重组NiV F胞外域三聚体的原聚体的C端残基(诸如三聚体茎区的残基)与跨膜结构域连接，用于NiV F F胞外域三聚体的膜锚定形式。

在一些实施方式中，重组NiV F胞外域三聚体与一个或更多个异源蛋白融合。例如，在一些实施方式中，重组NiV F胞外域三聚体的原聚体与NiV G胞外域融合，以提供NiVF-G嵌合体。在一些实施方式中，所述NiV F胞外域三聚体与至少三个NiV G胞外域连接，其中所述NiV G胞外域直接或通过肽接头间接与所述重组NiV F胞外域三聚体的原聚体的N端融合和/或与融合至所述重组NiV F胞外域三聚体的原聚体的C端的三聚结构域的C端融合。在一些实施方式中，所述三聚结构域包括，例如，GCN4三聚结构域、T4纤维蛋白三聚结构域，或GCN4三聚结构域和T4纤维蛋白三聚结构域。

在一些实施方式中，所述重组NiV F胞外域三聚体的原聚体进一步包括一个或更多个另外的突变，诸如将重组NiV F胞外域三聚体稳定在融合前构象的氨基酸取代，或抑制或防止F胞外域的F

在一些实施方式中，所述重组NiV F胞外域三聚体可以被包括在蛋白纳米颗粒(诸如铁蛋白蛋白纳米颗粒)上。

在一些实施方式中，提供了一种免疫原，所述免疫原包括融合蛋白的三聚体，每个融合蛋白在N端至C端方向上包括：一个或更多个NiV G胞外域和三聚结构域；三聚结构域和一个或更多个NiV G胞外域；或一个或更多个NiV G胞外域、三聚结构域以及一个或更多个NiV G胞外域。

在一些实施方式中，提供了一种蛋白纳米颗粒，诸如铁蛋白纳米颗粒，其包括单体NiV G胞外域。

还提供了编码公开的蛋白的核酸分子。例如，还提供了核酸分子，其编码以融合前构象稳定的公开的重组NiV F胞外域三聚体的前聚体、以融合前构象稳定的重组NiV F胞外域三聚体和一个或更多个G胞外域的嵌合体、NiV G胞外域的多聚体，或含有以融合前构象稳定的重组NiV F胞外域三聚体或NiV G胞外域的自组装蛋白纳米颗粒，以及包括核酸分子的载体及其产生方法。

还提供了包括适于向受试者施用的公开的免疫原的免疫原性组合物，并且该免疫原性组合物还可以包含在单位剂型中。免疫原还可以包含运载体以促进向免疫系统呈递。

公开了诱导受试者产生免疫应答的方法，以及公开了通过向受试者施用有效量的公开的免疫原、核酸分子或载体治疗、抑制或预防NiV感染的方法。

从以下参考附图进行的几个实施方式的详细描述，本公开的前述和其他特征和优点将变得更加显而易见。

附图说明

图1A-1F示出了NiV05(图1A)、NiV08(图1B)、NiV09(图1C)、NiV14(图1D)、NiV15(图1E)和NiV06(图1F)NiV F胞外域三聚体的负染电子显微镜(EM)图像和缎带(ribbon)图。

图2示出了单独或与靶向NiV F的融合前构象的5B3 Fab复合的NiVop08 NiV F胞外域三聚体的负染EM图像。

图3A-3C示出了体内免疫测定的示意图(图3A)和结果(图3B-3D)。图3B，通过Octet结合测定评估免疫小鼠的血清与融合前NiV F探针(NiVop08胞外域三聚体)和融合后NiV F探针(NiV06胞外域三聚体)的结合。图3C，对经指定的免疫原免疫小鼠的血清进行NiV中和评估。

图4示出了具有G-T4纤维蛋白三聚结构域(G-Fd)或G-T4纤维蛋白三聚结构域-G(G-Fd-G)形式的NiV G胞外域多聚体的负染EM。

图5A-5C示出了自组装的铁蛋白纳米颗粒的负染EM图像和缎带图，该铁蛋白纳米颗粒包含通过5个氨基酸的肽接头(图5A)、15个氨基酸的肽接头(图5B)或25个氨基酸的肽接头(图5C)与铁蛋白连接的NiV G胞外域。

图6A-6C示出了用于NiV G胞外域多聚体和含NiV G胞外域的铁蛋白纳米颗粒的体内免疫测定的示意图(图6A)和结果(图6B-6C)。图3B，通过Octet结合测定评估免疫小鼠的血清与单价NiV G探针的结合。图3C，对经指定的免疫原免疫小鼠的血清进行NiV中和评估。

图7A-7C示出了含有NiV F胞外域三聚体和三个单体NiV G胞外域的嵌合NiV F-G构建体的示意图(图7A)和负染EM图像(图7B和7C)。

图8A-8E示出了NiV F-G嵌合体的体内免疫测定的示意图(图8A)和结果(图8B-6E)。通过Octet结合测定法评估免疫小鼠的血清与融合前NiV F胞外域三聚体(图8B)、融合后NiV F胞外域三聚体(图8C)或NiV G胞外域三聚体(图8D)的结合。图8E，对经指定的免疫原免疫小鼠的血清进行NiV中和评估。

图9A-9D显示了在雪貂模型中NiV F、G和F-G嵌合免疫原的体内免疫测定的免疫方案和示意图(图9A和9B)以及结果(图9C-9D)。在16个不同的组中动物经preF、postF、G六聚体或preF/G嵌合体免疫原免疫。使用上述假病毒中和测定，对在第六周(图9C)和第九周(图9D)从免疫动物收集的血清进行NiV中和评估。

图10示出了使用体外细胞的活NiV感染的病毒中和试验(VNT)的结果，该试验使用来自preF、preF/G嵌合体和G-六聚体免疫原的10μg和100μg mRNA免疫条件的血清。

图11是示出NiV假病毒和活NiV的中和性的相关性的图。

图12A-12C示出了小鼠模型中NiV Pre-F、Post-F、WT-F、G-六聚体和G-四聚体(+柄)的体内免疫测定的免疫方案(图12A)和结果(图12B和12C)，具有多种变体，包括基于mRNA或蛋白的免疫、信号序列以及可溶性或膜锚定免疫原。

图12A-12C示出了小鼠模型中NiV Pre-F、Post-F、WT-F、G-六聚体和G-四聚体(+柄)的体内免疫测定的免疫方案(图12A)和结果(图12B和12C)，具有多种变异，包括基于mRNA或蛋白的免疫、信号序列以及可溶性或膜锚定免疫原。

图13A-13D示出了小鼠模型中NiV F、G和F/G嵌合免疫原的体内免疫测定的免疫方案和示意图(图13A和13B)以及结果(图13C-13D)。使用基于蛋白或mRNA的免疫系统，动物经preF、postF、G-六聚体或preF/G嵌合体免疫原免疫(图13B)。评估在第六周从免疫动物收集的血清的前F结合IgG(图13C)和G结合IgG(图13D)。

序列

如37C.F.R.1.822定义，使用核苷酸碱基的标准字母缩写和氨基酸的三个字母代码显示本文列出的核酸和氨基酸序列。每个核酸序列仅显示一条链，但对显示链的任何提及应理解为互补链包括在内。序列表以ASCII文本文件的形式提交，文件名为“Sequence.txt”(～396kb)，该文件于2019年8月1日创建，其通过引用并入本文。在随附的序列表中：

SEQ ID NO:1是包括NiV01蛋白的氨基酸序列。

SEQ ID NO:2是包括NiV02蛋白的氨基酸序列。

SEQ ID NO:3是包括NiV03蛋白的氨基酸序列。

SEQ ID NO:4是包括NiV04蛋白的氨基酸序列。

SEQ ID NO:5是包括NiV05蛋白的氨基酸序列。

SEQ ID NO:6是包括NiV06蛋白的氨基酸序列。

SEQ ID NO:7是包括NiV07蛋白的氨基酸序列。

SEQ ID NO:8是包括NiV08蛋白的氨基酸序列。

SEQ ID NO:9是包括NiV09蛋白的氨基酸序列。

SEQ ID NO:10是包括NiV10蛋白的氨基酸序列。

SEQ ID NO:11是包括NiV11蛋白的氨基酸序列。

SEQ ID NO:12是包括NiV12蛋白的氨基酸序列。

SEQ ID NO:13是包括NiV13蛋白的氨基酸序列。

SEQ ID NO:14是包括NiV14蛋白的氨基酸序列。

SEQ ID NO:15是包括NiV15蛋白的氨基酸序列。

SEQ ID NO:16是包括NiV16蛋白的氨基酸序列。

SEQ ID NO:17是包括NiVop01蛋白的氨基酸序列。

SEQ ID NO:18是包括NiVop02蛋白的氨基酸序列。

SEQ ID NO:19是包括NiVop03蛋白的氨基酸序列。

SEQ ID NO:20是包括NiVop04蛋白的氨基酸序列。

SEQ ID NO:21是包括NiVop05蛋白的氨基酸序列。

SEQ ID NO:22是包括NiVop06蛋白的氨基酸序列。

SEQ ID NO:23是包括NiVop07蛋白的氨基酸序列。

SEQ ID NO:24是包括NiVop08蛋白的氨基酸序列。

SEQ ID NO:25是包括NiVop09蛋白的氨基酸序列。

SEQ ID NO:26是包括NiVop12蛋白的氨基酸序列。

SEQ ID NO:27是包括NiVop13蛋白的氨基酸序列。

SEQ ID NO:28是包括NiVop14蛋白的氨基酸序列。

SEQ ID NO:29是包括NiVop15蛋白的氨基酸序列。

SEQ ID NO:30是包括NiVop16蛋白的氨基酸序列。

SEQ ID NO:31是包括NiVop17蛋白的氨基酸序列。

SEQ ID NO:32是包括NiVop18蛋白的氨基酸序列。

SEQ ID NO:33是编码具有NiVop08取代的全长NiV F的示例性核酸序列。

SEQ ID NO:34是包括Fd-G蛋白的氨基酸序列。

SEQ ID NO:35是包括Fd-GG蛋白的氨基酸序列。

SEQ ID NO:36是包括Fd-GGG蛋白的氨基酸序列。

SEQ ID NO:37是包括G-Fd-G蛋白(可溶性G-六聚体)的氨基酸序列。

SEQ ID NO:38是包括通过五氨基酸接头与铁蛋白亚基连接的NiV G的氨基酸序列(G-ln5-Fer)。

SEQ ID NO:39是包括通过15氨基酸接头与铁蛋白亚基连接的NiV G的氨基酸序列(G-ln15-Fer)。

SEQ ID NO:40是包括通过25氨基酸接头与铁蛋白亚基连接的NiV G的氨基酸序列(G-ln25-Fer)。

SEQ ID NO:41是包括通过35氨基酸接头与铁蛋白亚基连接的NiV G的氨基酸序列(G-ln35-Fer)。

SEQ ID NO:42是包括与二氧四氢蝶啶合酶亚基连接的NiV G的氨基酸序列(G-LS)。

SEQ ID NO:43是包括通过GCN4和Fd三聚结构域与NiV G连接的NiVop08的氨基酸序列(NiVop08-TD-G)。

SEQ ID NO:44是包括与连接至GCN4和Fd三聚结构域的NiVop09连接的NiVG的氨基酸序列(G–NiVop08-TD)。

SEQ ID NO:45是包括通过GCN4和Fd三聚结构域与NiV G连接的NiVop06的氨基酸序列(NiV06-TD-G)。

SEQ ID NO:46是包括通过GCN4和Fd三聚结构域与NiV G的两个拷贝连接的NiVop06的氨基酸序列(NiV06-TD-GG)。

SEQ ID NO:47是包括通过GCN4和Fd三聚结构域与NiV G的两个拷贝连接的NiVop08的氨基酸序列(NiVop08-TD-GG)。

SEQ ID NO:48是包括通过NCN4和Fd三聚结构域与NiV G的三个拷贝连接的NiVop06的氨基酸序列(NiV06-TD-GGG)。

SEQ ID NO:49是包括通过GCN4和Fd三聚结构域与NiV G的三个拷贝连接的NiVop08的氨基酸序列(NiVop08-TD-GGG)。

SEQ ID NO:50是包括与连接至GCN4和Fd三聚结构域的NiV06连接的NiV G的氨基酸序列(G-NiV06-TD)。

SEQ ID NO:51是包括与连接至GCN4和Fd三聚结构域的NiVop08连接的NIV G的氨基酸序列(G-NiVop08-TD)。

SEQ ID NO:52是野生型NiV F蛋白的示例性序列。

SEQ ID NO:53和54是野生型NiV G蛋白的示例性序列。

SEQ ID NO:55-58是蛋白纳米颗粒亚基的氨基酸序列。

SEQ ID NO:59是包括通过GCN4三聚结构域与NiV G连接的NiVop08的氨基酸序列(NiVop08-GCN4-G)。

SEQ ID NO:60是包括通过Fd三聚结构域与NiV G连接的NiVop08的氨基酸序列(NiVop08–Fd-G)。

SEQ ID NO:61是编码NiVop08–TD-G的示例性核酸序列。

SEQ ID NO:62是编码G–NiVop08-TD的示例性核酸序列。

SEQ ID NO:63是编码NiV08的示例性核酸序列。

SEQ ID NO:64是编码G-ln5-Ferritin的示例性核酸序列。

SEQ ID NO:65是编码NiVop08-GCN4-G的示例性核酸序列。

SEQ ID NO:66是编码NiVop08-Fd-G的示例性核酸序列。

SEQ ID NO:67是编码G-Fd-G的示例性核酸序列。

SEQ ID NO:68是HeV G蛋白的示例性序列。

SEQ ID NO:69和70是包含NiVop8和HeV G的嵌合蛋白的序列。

具体实施方式

本文公开了包括原聚体的重组NiV F胞外域三聚体，该原聚体包括使F胞外域三聚体以其融合前构象稳定的一个或更多个修饰(诸如氨基酸取代)。另外，提供了以融合前构象稳定的重组NiV F胞外域三聚体的嵌合体和一个或更多个G胞外域、NiV G胞外域的多聚体，以及包含以融合前构象稳定的重组NiV F胞外域三聚体或NiV G胞外域的自组装蛋白纳米颗粒。

与未以融合前构象稳定的相应的NiV F胞外域三聚体相比，融合前稳定的NiV F胞外域三聚体的实施方式被证明在动物模型中产生优异的免疫应答。几种融合前稳定的NiVF胞外域设计提供了出人意料的良好稳定性、均质性、产量和免疫原性组合。

类似地，公开的以融合前构象稳定的重组NiV F胞外域三聚体的嵌合体和一个或更多个G胞外域的实施方式提供了出人意料的良好稳定性、均质性、产量和免疫原组合，特别是考虑到这些构建体的嵌合方面。

I.术语概要

除非另有说明，否则根据常规用法使用技术术语。分子生物学中常用术语的定义可见于Benjamin Lewin,Genes X,Jones&Bartlett Publishers出版,2009；Meyers et al.(eds.),The Encyclopedia of Cell Biology and Molecular Medicine,Wiley-VCH出版，第16卷,2008；以及其他类似参考。如本文所用，单数形式“a”、“an”和“the”是指单数，也指复数，除非上下文另有指示。例如，术语“an antigen(抗原)”包括单个或多个抗原，并且可以被认为等同于短语“至少一个抗原”。如本文所用，术语“包括”是指“包含”。还应理解，除非另有说明，否则针对核酸或多肽给出的任何和所有碱基大小或氨基酸大小以及所有分子量或分子质量值均是近似的，并且出于描述性目的提供。尽管可以使用与本文描述的方法或材料相似或等同的许多方法和材料，但是下面描述了特定的合适的方法和材料。在发生冲突的情况下，以本说明书(包括术语解释)为准。另外，材料、方法和实施例仅是说明性的，并不旨在限制。为了便于查看各种实施实施方式，提供以下术语解释：

佐剂(adjuvant)：用于增强抗原性的媒介(vehicle)。在一些实施方式中，佐剂包括矿物质(铝、氢氧化铝或磷酸盐)的悬浮液，其上吸附有抗原；或油包水乳剂，例如，其中抗原溶液在矿物油中乳化(弗氏不完全佐剂)，有时包含杀死的分枝杆菌(弗氏完全佐剂)以进一步增强抗原性(抑制抗原降解和/或导致巨噬细胞流入)。在一些实施方式中，在公开的免疫原性组合物中使用的佐剂是卵磷脂和卡波姆均聚物的组合(诸如获自AdvancedBioAdjuvants，LLC的ADJUPLEX

施用(administration)：通过选择的途径将组合物引入受试者。施用可以是局部的，也可以是全身的。例如，如果选择的途径是鼻内，则通过将组合物引入受试者的鼻道中来施用组合物(诸如包括公开的重组NiV F胞外域的组合物)。示例性施用途径包括但不限于口服、注射(诸如皮下、肌内、真皮内、腹腔和静脉内)、舌下、直肠、经皮(例如局部)、鼻内、阴道和吸入途径。

氨基酸取代(amino acid substitution)：用一种或更多种不同的氨基酸取代多肽中的氨基酸。在蛋白序列的背景下，氨基酸取代也称为突变。

抗体(antibody)：免疫球蛋白、抗原结合片段或其衍生物，可以特异性结合并识别分析物(抗原)(诸如NiV F蛋白)、其抗原片段或抗原的二聚体或多聚体。术语“抗体”在本文中以最广义使用，并且涵盖各种抗体结构，包括但不限于单克隆抗体、多克隆抗体、多特异性抗体(例如，双特异性抗体)和抗体片段，只要它们表现出预期的抗原结合活性即可。抗体的非限制性实例包括，例如，完整的免疫球蛋白及其保留对抗原的结合亲和力的变体和片段。抗体片段的实例包括但不限于Fv、Fab、Fab'、Fab'-SH、F(ab')

运载体(carrier)：可以与抗原连接的免疫原性分子。当与运载体连接时，抗原可能变得更具免疫原性。选择运载体以增加抗原的免疫原性和/或引发针对运载体的抗体，其在诊断、分析和/或治疗上有益。有用的运载体包括聚合物运载体，其可以是天然的(例如，来自细菌或病毒的蛋白)，含有一个或更多个可以附着反应物部分的官能团的半合成或合成材料。

空腔填充氨基酸取代(cavity-filling amino acid substitution)：填充蛋白的蛋白核心(诸如NiV F胞外域)内空腔的氨基酸取代。空腔本质上是折叠蛋白内的空隙，其中不存在氨基酸或氨基酸侧链。在一些实施方式中，引入空腔填充氨基酸取代以填充存在于在转变为融合后构象后塌陷(例如，体积减小)的NiV F胞外域核心的融合前构象中的空腔。

保守变体(conservative variants)：“保守的”氨基酸取代是基本上不影响或降低蛋白功能(诸如当施用于受试者时蛋白诱导免疫应答的能力)的那些取代。术语保守变体还包括使用取代的氨基酸代替未被取代的亲本氨基酸。此外，在编码序列中改变、添加或缺失单个氨基酸或少量氨基酸(例如小于5％，在一些实施方式中小于1％)的单个取代、缺失或添加是保守变异，其中这些改变导致氨基酸被化学上相似的氨基酸取代。

以下六组是被认为是彼此保守取代的氨基酸实例：

1)丙氨酸(A)，丝氨酸(S)，苏氨酸(T)；

2)天冬氨酸(D)，谷氨酸(E)；

3)天冬酰胺(N)，谷氨酰胺(Q)；

4)精氨酸(R)，赖氨酸(K)；

5)异亮氨酸(I)，亮氨酸(L)，蛋氨酸(M)，缬氨酸(V)；和

6)苯丙氨酸(F)，酪氨酸(Y)，色氨酸(W)。

非保守取代是降低重组NiV F胞外域三聚体的活性或功能的取代，诸如当施用于受试者时诱导免疫应答的能力。例如，如果氨基酸残基对于蛋白的功能必不可少，则即使不然为保守的取代也可能破坏该活性。因此，保守取代不会改变目的蛋白的基本功能。

对照(control)：参考标准。在一些实施方式中，对照是获自健康患者的阴性对照样品。在其他实施方式中，对照是获自诊断为NiV感染的患者的阳性对照样品。在其他实施方式中，对照是历史对照或标准参考值或值的范围(诸如先前检测的对照样品，诸如具有已知预后或结局的一组NiV患者，或代表基线或正常值的一组样品)。

检测样品和对照之间的差异可以是增加或，相反地，减少。差异可以是定性差异或定量差异，例如统计学上显著差异。在一些实例中，差异是相对于对照增加或减少至少约5％，诸如至少约10％、至少约20％、至少约30％、至少约40％、至少约50％、至少约60％、至少约70％、至少约80％、至少约90％、至少约100％、至少约150％、至少约200％、至少约250％、至少约300％、至少约350％、至少约400％、至少约500％或大于500％。

简并变体(degenerate variant)：在本公开的上下文中，“简并变体”是指编码多肽的多核苷酸，其包括由于遗传密码而简并的序列。有20种天然氨基酸，其中大多数由多于一个的密码子指定。因此，包括所有编码肽的简并核苷酸序列，只要由核苷酸序列编码的肽的氨基酸序列不变即可。

有效量(effective amount)：足以引起受试者产生预期应答(诸如免疫应答)的试剂(诸如免疫原)的量。应当理解，欲获得针对目的抗原的保护性免疫应答，可能需要多次施用公开的免疫原，和/或以初次加强免疫方案的“初次免疫”方式施用公开的免疫原，其中加强免疫原可以不同于初次免疫原。因此，公开的免疫原的有效量可以是足以引起受试者产生初次免疫应答的免疫原的量，其随后可以用相同或不同的免疫原加强以引发保护性免疫应答。

在一个实例中，预期应答是抑制或减少或预防NiV感染。对于该方法有效而言，不需要完全消除或减少或预防NiV感染。例如，施用有效量的试剂可以将NiV感染(例如，通过细胞感染或通过NiV感染的受试者的数量或百分比来测量)降低预期量，例如与合适的对照相比，降低至少50％、至少60％、至少70％、至少80％、至少90％、至少95％、至少98％或甚至至少100％(消除或预防可检测的NiV感染)。

表达(expression)：核酸序列的转录或翻译。例如，当基因的DNA转录为RNA或RNA片段(在一些实例中，其被加工成mRNA)时，该基因表达。当基因的mRNA翻译成氨基酸序列(诸如蛋白或蛋白片段)时，也可以表达该基因。在特定的实例中，当异源基因被转录成RNA时，其被表达。在另一实例中，当其RNA翻译成氨基酸序列时，异源基因被表达。本文使用术语“表达”表示转录或翻译。表达的调节可包括控制转录、翻译、RNA运输和加工、中间分子(诸如mRNA)的降解，或通过特定蛋白分子在产生后的活化、失活、区室化或降解。

表达控制序列(expression control sequences)：调节与之可操作地连接的异源核酸序列表达的核酸序列。当表达控制序列控制和调节核酸序列的转录和翻译(视情况)时，将表达控制序列可操作地连接至核酸序列。因此，表达控制序列可以包括合适的启动子、增强子、转录终止子、蛋白编码基因前的起始密码子(ATG)、内含子的剪接信号，维持该基因的正确阅读框架，以允许mRNA的正确翻译，以及终止密码子。术语“控制序列”旨在至少包括其存在可以影响表达的组分，并且还可以包括其存在有利的其他组分，例如前导序列和融合配偶体序列。表达控制序列可以包括启动子。

启动子是足以指导转录的最小序列。还包括那些启动子元件，其足以使启动子依赖性基因表达对于细胞类型特异性、组织特异性是可控的或可被外部信号或试剂诱导；这样的元件可以位于基因的5'或3'区域。组成型和诱导型启动子均包括在内(参见，例如，Bitter et al.,Methods in Enzymology 153:516-544,1987)。例如，当在细菌系统中克隆时，可以使用诱导型启动子，诸如噬菌体λ的pL、plac、ptrp、ptac(ptrp-lac杂合启动子)等。在一个实施方式中，当在哺乳动物细胞系统中克隆时，源自哺乳动物细胞基因组的启动子(诸如金属硫蛋白启动子)或源自哺乳动物病毒的启动子(诸如逆转录病毒长末端重复序列；腺病毒晚期启动子；牛痘病毒7.5K启动子)可以使用。通过重组DNA或合成技术产生的启动子也可以用于提供核酸序列的转录。

表达载体(expression vector)：包括重组多核苷酸的载体，其包括可操作地连接至待表达核苷酸序列的表达控制序列。表达载体包括用于表达足够的顺式作用元件。其他表达元件可以由宿主细胞或在体外表达系统中提供。表达载体包括本领域已知的所有载体，诸如粘粒、质粒(例如，裸露或包含在脂质体中)和病毒(例如，慢病毒、逆转录病毒、腺病毒和腺相关病毒)，其掺入重组多核苷酸。

GCN4三聚结构域(GCN4 trimerization domain)：来自GCN4蛋白的三聚结构域，其包括天然形成三聚体结构的亮氨酸拉链氨基酸序列。GCN4三聚结构域的实施方式描述于，例如，Harbury et al.(1993Science 262:1401-1407)。在一些实例中，GCN4三聚结构域可以被包括在公开的重组蛋白的氨基酸序列中，使得重组蛋白将三聚化。提供与公开的实施方式一起使用的GCN4三聚结构域序列的非限制性实例，如KLMKQIEDKIEEILSKIYHIENEIARIKKLIGEAP(SEQ ID NO:1的残基485-519)。

异源(heterologous)：源自不同的遗传来源。

宿主细胞(host cells)：载体可在其中繁殖并表达其核酸的细胞。该细胞可以是原核的或真核的。该术语还包括受试者宿主细胞的任何后代。应当理解，所有后代可能与亲代细胞并不相同，因为在复制过程中可能发生突变。然而，当使用术语“宿主细胞”时，包括这种后代。

免疫应答(immune response)：免疫系统细胞(诸如B细胞、T细胞或单核细胞)对刺激产生的应答。在一个实施方式中，该应答对特定抗原具有特异性(“抗原特异性应答”)。在一个实施方式中，免疫应答是T细胞应答，诸如CD4+应答或CD8+应答。在另一实施方式中，该应答是B细胞应答，并导致产生特异性抗体。

免疫原(immunogen)：可以引起动物产生免疫应答的化合物、组合物或物质(例如重组NiV F胞外域三聚体)，包括注射或吸收到动物体内的组合物。向受试者施用免疫原可导致针对目的病原体的保护性免疫。

免疫原性组合物(immunogenic composition)：包括公开的重组NiV F胞外域三聚体的组合物，当施用于受试者时，其诱导针对NiV的可测量的CTL应答，或诱导针对NiV的可测量的B细胞应答(诸如产生抗体)。它还进一步指编码公开的重组NiV F胞外域三聚体的原聚体的分离的核酸分子和载体，其可用于表达该原聚体(并因此用于引起针对重组NiV F胞外域三聚体的免疫应答)。对于体内使用，免疫原性组合物通常在药学上可接受的载体中包含重组NiV F胞外域三聚体或编码重组NiV F胞外域三聚体的原聚体的核酸分子，并且还可以包括其他试剂，诸如佐剂。

抑制或治疗疾病(inhibiting or treating a disease)：例如，在有疾病如NiV感染风险的受试者中，抑制疾病或病症的全面发展。“治疗”是指在疾病或病理病症开始发展后减轻其症状或体征的治疗性干预措施。关于疾病或病理病症，术语“改善”是指治疗的任何可观察到的有益作用。抑制疾病可以包括预防或降低疾病的风险，诸如预防或降低病毒感染的风险。可以例如通过在易感受试者中疾病的临床症状的延迟发作、疾病的一些或全部临床症状的严重程度降低、疾病进展减慢、病毒载量降低、受试者总体健康或生活质量的改善、或特定于特定疾病的其他参数来证明有益效果。“预防性”治疗是施用于未表现出疾病体征或仅表现出早期体征以降低发生病理的风险的受试者的治疗。

分离的(isolated)：“分离的”生物组分已与其他生物组分(诸如该组分存在于其中的天然存在的其他生物组分，诸如其他染色体和染色体外DNA、RNA和蛋白)基本分离或纯化。已“分离的”蛋白、肽、核酸和病毒包括通过标准纯化方法纯化的蛋白、肽、核酸和病毒。分离不需要绝对的纯度，可以包括至少50％分离的蛋白、肽、核酸或病毒分子，诸如至少75％、80％、90％、95％、98％、99％或甚至99.9％分离的。

接头(linker)和连接的(linked)：可用于将两个分子连接成一个连续分子的双功能分子。肽接头的非限制性实例包括甘氨酸-丝氨酸肽接头。除非上下文另有说明，否则提及将第一多肽和第二多肽“连接”，或将两个“连接”在一起的多肽或具有“连接”到第二多肽的第一个多肽指通过肽键共价连接(例如通过肽接头)，使得第一和第二多肽形成连续的多肽链。如果涉及肽接头，则第一和第二多肽的共价连接可以是该肽接头的N端和C端。通常，使用分子生物学技术通过遗传操作编码通过肽接头连接至第二多肽的第一多肽的DNA来完成这种连接。

天然蛋白(native protein)、序列(sequence)或二硫键(disulfide bond)：未经修饰(例如，通过选择性突变)的多肽、序列或二硫键。例如，选择性突变将抗原的抗原性集中于靶表位，或将二硫键引入蛋白中，而天然蛋白中不会发生这种情况。天然蛋白或天然序列也称为野生型蛋白或野生型序列。非天然二硫键是天然蛋白中不存在的二硫键，例如，由于通过基因工程将一个或更多个半胱氨酸残基引入蛋白而在蛋白中形成的二硫键。

尼帕病毒(Nipah Virus，NiV)：亨尼帕病毒(Nipah henipavirus)是副粘病毒科的一种有包膜的非节段负链单链RNA病毒。NiV基因组的长度约为18,000个核苷酸，包括6个基因编码9种蛋白，其中包括糖蛋白G和F。示例性天然NiV菌株序列是本领域普通技术人员已知的。可获得人NiV感染的几种模型，包括被NiV感染的模式生物，诸如雪貂、小鼠、金仓鼠、豚鼠和非洲绿猴(参见，例如，Geisbert et al.,Curr.Top.Microbiol.Immunol.,359:153-77,2012，其通过引用以其全文并入本文)。

天然的NiV宿主是狐蝠科的果蝠。从无症状感染到急性呼吸道综合征和致命性脑炎，人NiV感染具有一系列临床表现。NiV还能够引起猪和其他家畜疾病。在人类中，NiV感染通常表现为发烧、头痛和嗜睡。咳嗽、腹痛、恶心、呕吐、无力、吞咽问题和视力模糊相对普遍。约四分之一的人类患者患有癫痫，并且约60％昏迷，并可能需要机械通气。在患有重度疾病的患者中，他们的意识状态可能恶化，并可能发展为重度高血压、心率加快和体温极高。

NiV附着糖蛋白(G)：一种NiV包膜糖蛋白，是II型膜蛋白，可促进NiV附着在宿主细胞膜上。全长G蛋白具有N端细胞质尾和跨膜结构域(CT和TM，约氨基酸1-176)和胞外结构域(约氨基酸177-602)。本文提供了从马来西亚株(Malaysianstain)得到的NiV G的示例性NiV G蛋白序列，如SEQ ID NO:53(NCBI参考序列NP_112027.1，其通过引用并入本文)：

MPAENKKVRFENTTSDKGKIPSKVIKSYYGTMDIKKINEGLLDSKILSAFNTVIALLGSIVIIVMNIMIIQNYTRSTDNQAVIKDALQGIQQQIKGLADKIGTEIGPKVSLIDTSSTITIPANIGLLGSKISQSTASINENVNEKCKFTLPPLKIHECNISCPNPLPFREYRPQTEGVSNLVGLPNNICLQKTSNQILKPKLISYTLPVVGQSGTCITDPLLAMDEGYFAYSHLERIGSCSRGVSKQRIIGVGEVLDRGDEVPSLFMTNVWTPPNPNTVYHCSAVYNNEFYYVLCAVSTVGDPILNSTYWSGSLMMTRLAVKPKSNGGGYNQHQLALRSIEKGRYDKVMPYGPSGIKQGDTLYFPAVGFLVRTEFKYNDSNCPITKCQYSKPENCRLSMGIRPNSHYILRSGLLKYNLSDGENPKVVFIEISDQRLSIGSPSKIYDSLGQPVFYQASFSWDTMIKFGDVLTVNPLVVNWRNNTVISRPGQSQCPRFNTCPEICWEGVYNDAFLIDRINWISAGVFLDSNQTAENPVFTVFKDNEILYRAQLASEDTNAQKTITNCFLLKNKIWCISLVEIYDTGDNVIRPKLFAVKIPEQCT

本文提供了从孟加拉株(Bangladeshstain)得到的NiV G的示例性NiV G蛋白序列，如SEQ ID NO:54(GenBank参考号AAY43916.1，其通过引用并入本文)：

MPTESKKVRFENTASDKGKNPSKVIKSYYGTMDIKKINEGLLDSKILSAFNTVIALLGSIVIIVMNIMIIQNYTRSTDNQAMIKDALQSIQQQIKGLADKIGTEIGPKVSLIDTSSTITIPANIGLLGSKISQSTASINENVNEKCKFTLPPLKIHECNISCPNPLPFREYKPQTEGVSNLVGLPNNICLQKTSNQILKPKLISYTLPVVGQSGTCITDPLLAMDEGYFAYSHLEKIGSCSRGVSKQRIIGVGEVLDRGDEVPSLFMTNVWTPSNPNTVYHCSAVYNNEFYYVLCAVSVVGDPILNSTYWSGSLMMTRLAVKPKNNGESYNQHQFALRNIEKGKYDKVMPYGPSGIKQGDTLYFPAVGFLVRTEFKYNDSNCPIAECQYSKPENCRLSMGIRPNSHYILRSGLLKYNLSDEENSKIVFIEISDQRLSIGSPSKIYDSLGQPVFYQASFSWDTMIKFGDVQTVNPLVVNWRDNTVISRPGQSQCPRFNKCPEVCWEGVYNDAFLIDRINWISAGVFLDSNQTAENPVFTVFKDNEVLYRAQLASEDTNAQKTITNCFLLKNKIWCISLVEIYDTGDNVIRPKLFAVKIPEQCT

如本文所用，NiV G残基定位参照SEQ ID NO:53所示的序列进行。

NiV融合(F)蛋白：NiV的包膜糖蛋白，可促进病毒和细胞膜融合。实际上，最初将来自NiV的F蛋白合成为单个多肽前体，长度约为550个氨基酸，称为F

NiV F蛋白在NiV株内显示出显著的序列保守性。考虑到这种保守性，本领域普通技术人员可以容易地比较不同NiV F蛋白的氨基酸位置。除非上下文另有说明，否则NiV F氨基酸的编号参照SEQ ID NO:52(NCBI参考序列NP_112026.1，其通过引用并入本文)：

MVVILDKRCYCNLLILILMISECSVGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSQCTGSVMENYKTRLNGILTPIKGALEIYKNNTHDLVGDVRLAGVIMAGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVLTALQDYINTNLVPTIDKISCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLISMLSMIILYVLSIASLCIGLITFISFIIVEKKRNTYSRLEDRRVRPTSSGDLYYIGT

三个NiV F原聚体在成熟的F蛋白中寡聚，其采取亚稳态融合前构象，当与靶细胞膜接触时，该构象被触发发生构象变化，变为融合后构象。这种构象变化会暴露称为融合肽的疏水序列，其位于F

与相应的天然NiV F序列相比，“以融合前构象稳定”的NiV F胞外域三聚体包括一个或更多个氨基酸取代、缺失或插入，与由相应的天然NiV F序列形成的NiV F胞外域三聚体相比，其提供融合前构象保留的增加。融合前构象的“稳定”可以是例如能量稳定(例如，相对于融合后开放构象，降低融合前构象的能量)和/或动力学稳定(例如，降低从融合前构象向融合后构象的转变速率)。另外，与相应的天然NiV F序列相比，在融合前构象中NiV F胞外域三聚体的稳定可以包括对变性的抗性增加。本文提供了确定NiV F胞外域三聚体是否处于融合前构象中的方法，包括(但不限于)负染色电子显微镜和使用融合前构象特异性抗体(诸如5B3抗体)的抗体结合测定。

NiV F融合前特异性抗体(NiV F prefusion specific antibody)：与融合前构象NiV F蛋白特异性结合，但不与融合后构象NiV F蛋白特异性结合的抗体。例如，US2016/0347827中公开的5B3抗体(通过引用以其全文并入本文)是NiV融合前特异性抗体。

核酸分子(nucleic acid molecule)：核苷酸的聚合形式，可以包括RNA、cDNA、基因组DNA的有义链和反义链，以及上述的合成形式和混合聚合物。核苷酸是指核糖核苷酸、脱氧核苷酸或任一类型核苷酸的修饰形式。本文所用的术语“核酸分子”与“核酸”和“多核苷酸”同义。除非另有说明，否则核酸分子的长度通常至少为10个碱基。该术语包括DNA的单链和双链形式。多核苷酸可以包括通过天然存在的和/或非天然存在的核苷酸键连接在一起的天然存在的核苷酸和修饰的核苷酸之一或二者。“cDNA”是指与mRNA互补或相同的DNA，呈单链或双链形式。“编码”是指多核苷酸中特定核苷酸序列的固有特性，诸如基因、cDNA或mRNA，在具有确定核苷酸序列的生物过程中用作合成其他聚合物和大分子的模板(即，rRNA、tRNA和mRNA)或确定的氨基酸序列以及由此产生的生物学特性。

可操作地连接(operably linked)：当第一核酸序列与第二核酸序列处于功能关系时，第一核酸序列与第二核酸序列可操作地连接。例如，如果启动子影响编码序列的转录或表达，则将其与编码序列可操作地连接。通常，可操作连接的核酸序列是连续的，并且在需要连接两个蛋白编码区的情况下，在同一阅读框中。

药学上可接受的载体(pharmaceutically acceptable carriers)：药学上可接受的载体是常规的。Remington’s Pharmaceutical Sciences,by E.W.Martin,MackPublishing Co.,Easton,PA,19th Edition,1995描述了适用于公开的免疫原的药物递送的组合物和制剂。

通常，载体的性质将取决于所采用的特定施用方式。例如，肠胃外制剂通常包括可注射的流体，其包括药学和生理学上可接受的流体，诸如水、生理盐水、平衡盐溶液、葡萄糖水溶液、甘油等作为溶媒。对于固体组合物(例如，粉末、丸剂、片剂或胶囊剂形式)，常规的无毒固体载体可以包括，例如，药用级的甘露醇、乳糖、淀粉或硬脂酸镁。除生物中性载体外，待施用的药物组合物(诸如免疫原性组合物)可以包含少量的无毒辅助物质，诸如润湿剂或乳化剂、防腐剂和pH缓冲剂等，例如乙酸钠或脱水山梨糖醇单月桂酸酯。在特定实施方式中，适合于施用于受试者的载体可以是无菌的，和/或悬浮于或以其他方式包含在单位剂型中，该单位剂型包含一种或更多种测定剂量的适合于诱导预期免疫应答的组合物。它也可能伴随药物用于治疗目的。单位剂型可以例如在包含无菌内容物的密封小瓶中或用于向受试者注射的注射器中，或冻干以用于随后的增溶和施用，或者以固体或控释给药。

多肽(polypeptide)：任何氨基酸链，无论长度或翻译后修饰(例如，糖基化或磷酸化)。“多肽”适用于氨基酸聚合物，包括天然存在的氨基酸聚合物和非天然存在的氨基酸聚合物，以及其中一个或更多个氨基酸残基是非天然氨基酸的氨基酸聚合物，例如，相应天然氨基酸的人工模拟物。“残基”是指通过酰胺键或酰胺键模拟物掺入多肽的氨基酸或氨基酸模拟物。多肽具有氨基末端(N端)和羧基末端(C端)。“多肽”与肽或蛋白互换使用，并且在本文中用于指氨基酸残基的聚合物。

初免-加强疫苗接种(prime-boost vaccination)：一种免疫疗法，包括向受试者施用第一免疫原性组合物(初免疫苗)，然后向受试者施用第二免疫原性组合物(加强疫苗)以诱导免疫应答。初免疫苗和/或加强疫苗包括表达免疫应答所针对的抗原的载体(诸如病毒载体、RNA或DNA载体)。在初免疫苗之后将加强疫苗施用于受试者；在本文中公开了在施用初免疫苗和加强疫苗之间的合适时间间隔，以及这样的时间框架的实例。在一些实施方式中，初免疫苗、加强疫苗或初免疫苗和加强疫苗均另外包括佐剂。在一个非限制性实例中，初免疫苗是基于DNA的疫苗(或基于基因递送的其他疫苗)，并且加强疫苗是基于蛋白亚基或蛋白纳米颗粒的疫苗。

蛋白纳米颗粒(protein nanoparticle)：基于蛋白的自组装、多亚基、多面体形结构。每个亚基由蛋白或多肽(例如糖基化的多肽)以及任选地以下的单个或多个特征组成：核酸、辅基、有机和无机化合物。蛋白纳米颗粒的非限制性实例包括铁蛋白纳米颗粒(参见，例如，Zhang,Y.Int.J.Mol.Sci.,12:5406-5421,2011，其通过引用并入本文)、囊包蛋白(encapsulin)纳米颗粒(参见，例如，Sutter et al.,Nature Struct.and Mol.Biol.,15:939-947,2008，其通过引用并入本文)、硫氧化酶还原酶(SOR)纳米颗粒(参见，例如，Urichet al.,Science,311:996-1000,2006，其通过引用并入本文)、二氧四氢蝶啶(lumazine)合酶(参见，例如，Zhang et al.,J.Mol.Biol.,306:1099-1114,2001)或丙酮酸脱氢酶纳米颗粒(参见，例如，Izard et al.,PNAS 96:1240-1245,1999，通过引用并入本文)。铁蛋白、囊包蛋白、SOR、二氧四氢蝶啶合酶和丙酮酸脱氢酶是单体蛋白，它们自组装成球状蛋白复合物，在某些情况下分别由24、60、24、60和60个蛋白亚基组成。在一些实例中，铁蛋白、囊包蛋白、SOR、二氧四氢蝶啶合酶或丙酮酸脱氢酶单体与重组NiV F胞外域连接，并自组装成蛋白纳米颗粒，在其表面上呈现重组NiV F胞外域三聚体或NiV G胞外域，可以将其施用于受试者以刺激抗原的免疫应答。

重组(recombinant)：重组核酸分子是具有非天然存在序列的核酸分子，例如，包括一个或更多个核酸取代、缺失或插入，和/或具有由两个不然就为分离的序列区段的人工组合制成的序列。这种人工组合可以通过化学合成或更普遍地通过人工操作分离的核酸片段，例如通过基因工程技术完成。

重组病毒是包括包含重组核酸分子的基因组的病毒。

重组蛋白是具有非天然存在的序列或具有通过两个不然就为分离的序列片段的人工组合制成的序列的蛋白。在几个实施方式中，重组蛋白由已引入宿主细胞(诸如细菌或真核细胞)或重组病毒基因组中的异源(例如重组)核酸编码。

序列同一性(sequence identity)：氨基酸序列之间的相似性以序列之间的相似性表示，也称为序列同一性。序列同一性经常用百分比同一性来衡量；百分比越高，两个序列越相似。当使用标准方法比对时，多肽的同系物、直系同源物或变体将具有较高程度的序列同一性。

用于比较的序列比对方法是本领域熟知的。各种程序和比对算法描述于：Smith&Waterman,Adv.Appl.Math.2:482,1981；Needleman&Wunsch,J.Mol.Biol.48:443,1970；Pearson&Lipman,Proc.Natl.Acad.Sci.USA 85:2444,1988；Higgins&Sharp,Gene,73:237-44,1988；Higgins&Sharp,CABIOS 5:151-3,1989；Corpet et al.,Nuc.Acids Res.16:10881-90,1988；Huang et al.Computer Appls.In the Biosciences 8,155-65,1992；和Pearson et al.,Meth.Mol.Bio.24:307-31,1994.Altschul et al.,J.Mol.Biol.215:403-10,1990，提出了序列比对方法和同源性计算的详细考虑。

多肽的变体通常特征在于，在与目的氨基酸序列进行全长比对中计算时，拥有至少约75％，例如至少约80％、85％、90％、91％、92％、93％、94％、95％、96％、97％，98％或99％的序列同一性。当通过该方法评估时，与参考序列具有更高相似性的蛋白将显示出更高的同一性百分比，例如至少80％、至少85％、至少90％、至少95％、至少98％或至少99％的序列同一性。当比较少于整个序列的序列同一性时，同源物和变体通常在10-20个氨基酸的短窗口内具有至少80％序列同一性，并且根据与参考序列的相似性，它们可能具有至少85％或至少90％或95％的序列同一性。在这样的短窗口内确定序列同一性的方法可在互联网上的NCBI网站上获得。

如本文所用，提及“至少90％同一性”(或类似语言)是指“与指定参考序列具有至少90％、至少91％、至少92％、至少93％、至少94％、至少95％、至少96％、至少97％、至少98％、至少99％或甚至100％同一性”。

信号肽(signal Peptide)：短氨基酸序列(例如，长度约18-25个氨基酸)，指导新合成的分泌蛋白或膜蛋白至膜并通过膜(例如内质网膜)。信号肽通常位于多肽的N端，并在多肽穿过膜后被信号肽酶去除。信号肽序列通常包含三个共同的结构特征：N端极性碱性区域(n-区域)、疏水核心和亲水性c-区域)。示例性的信号肽序列如MYSMQLASCVTLTLVLLVNS(SEQ ID NO:1(NiV01)的残基1-20)所示

特异性结合(specifically bind)：当指抗体：抗原蛋白复合物或蛋白：蛋白复合物的形成时，是指在存在蛋白和其他生物制剂的异质群体的情况下，确定靶蛋白、肽或多糖(例如糖蛋白)存在的结合反应。因此，在指定条件下，特定的抗体或蛋白优先结合特定的目标蛋白、肽或多糖(诸如病原体表面上存在的抗原，例如，NiV F胞外域膜三聚体远端的抗原位点)，并且不会与样品或受试者中存在的其他蛋白或多糖大量结合。特异性结合可以通过本领域已知的方法确定。当相互作用的K

可溶性蛋白(soluble protein)：能够在室温下溶于水性液体并保持溶解状态的蛋白。蛋白的溶解度可以根据水基液体中蛋白的浓度、液体的缓冲条件、液体中其他溶质的浓度(例如盐和蛋白的浓度)以及液体的热量而变化。在一些实施方式中，可溶性蛋白是在室温下在磷酸盐缓冲液(pH 7.4)中溶解至少0.5mg/ml的浓度并且保持溶解至少48小时的蛋白。

受试者(subject)：活的多细胞脊椎动物，包括人类和非人类哺乳动物。在实例中，受试者是人类。在特定实例中，受试者是新生婴儿。在另外的实例中，选择需要抑制NiV感染的受试者。例如，该受试者未感染且有NiV感染的风险或被感染需要治疗。

T4纤维蛋白三聚结构域(T4 fibritin trimerization domain)：也称为“foldon”结构域，T4纤维蛋白三聚结构域包括天然形成三聚体结构的氨基酸序列。在一些实例中，T4纤维蛋白三聚结构域可以被包括在公开的重组蛋白的氨基酸序列中，使得抗原将形成三聚体。在一个实例中，T4纤维蛋白三聚结构域包括如(GYIPEAPRDGQAYVRKDGEWVLLSTF(SEQ IDNO:34的残基24-49)所示的氨基酸序列。几个实施方式包括可以从纯化的蛋白切割的T4纤维蛋白三聚结构域，用于例如通过掺入与T4纤维蛋白三聚结构域相邻的凝血酶切割位点以用于切割目的。

跨膜结构域(transmembrane domain)：插入脂质双层(诸如细胞或病毒或病毒样颗粒的脂质双层)中的氨基酸序列。跨膜结构域可用于将抗原锚定至膜。在一些实例中，跨膜结构域是NiV F跨膜结构域。

在足以满足的条件下：用于描述允许进行预期活动的任何环境的短语。

疫苗(vaccine)：能够刺激免疫应答的免疫原性材料制剂，用于预防、改善或治疗感染性或其他类型的疾病。免疫原性材料可以包括减毒或杀死的微生物(诸如细菌或病毒)，或抗原蛋白、肽或衍生自它们的DNA。疫苗可以包括公开的免疫原(诸如重组NiV F胞外域三聚体或编码其的核酸分子)、病毒、细胞或一种或更多种细胞成分。疫苗可以引起预防性(预防性或保护性)和治疗性应答。施用方法因疫苗而异，但可能包括接种、摄入、吸入或其他形式的施用。疫苗可以与佐剂共同施用以增强免疫应答。在一个具体的非限制性实例中，与对照相比，疫苗预防和/或降低了与NiV感染有关的症状的严重程度和/或降低了病毒载量。

载体(vector)：包含携带启动子的DNA或RNA分子的实体，该启动子可操作地连接至目的抗原的编码序列，并可以表达该编码序列。非限制性实例包括裸露或包装的(脂质和/或蛋白)DNA、裸露或包装的RNA、病毒或细菌或其他可能不具有复制能力的微生物的亚成分、或可能具有复制能力的病毒或细菌或其他微生物。载体有时称为构建体。重组DNA载体是具有重组DNA的载体。载体可以包括允许其在宿主细胞中复制的核酸序列，诸如复制起点。载体还可以包括一个或更多个选择标记基因和本领域已知的其他基因元件。病毒载体是具有至少一些衍生自一种或更多种病毒的核酸序列的重组核酸载体。

病毒样颗粒(virus-like particle，VLP)：非复制的病毒壳，衍生自多种病毒中的任何一种。VLP通常由一种或更多种病毒蛋白组成，例如但不限于被称为衣壳蛋白、外壳蛋白、壳蛋白、表面蛋白和/或包膜蛋白的那些蛋白，或衍生自这些蛋白的形成颗粒的多肽。在适当的表达系统中重组表达蛋白后，VLP可以自发形成。产生特定VLP的方法是本领域已知的。重组表达病毒蛋白后VLP的存在可以使用本领域已知的常规技术来检测，诸如通过电子显微镜、生物物理表征等。此外，可以通过已知技术例如密度梯度离心法分离VLP，并通过特征密度条带来鉴定。参见，例如，Baker et al.(1991)Biophys.J.60:1445-1456；andHagensee et al.(1994)J.Virol.68:4503-4505；Vincente,J Invertebr Pathol.,2011；Schneider-Ohrum and Ross,Curr.Top.Microbiol.Immunol.,354:53073,2012)。

II.免疫原

A.重组NiV F胞外域三聚体

本文公开了由天然形式修饰的重组NiV F胞外域三聚体(例如，通过引入一个或更多个氨基酸取代)，以使其以融合前构象稳定。如实施例中所述，已通过多轮基于结构的设计选择了所公开的NiV F胞外域三聚体的实施方式，以优化溶解度、稳定性、表达和免疫原性。重组NiV F胞外域三聚体可用于诱导脊椎动物(如人)产生对NiV的免疫应答。与未以融合前构象稳定的相应的NiV F胞外域三聚体相比，示例性实施方式显示在动物模型中产生优异的免疫应答。

在一些实施方式中，免疫原包括重组NiV F胞外域三聚体，其包括原聚体，该原聚体包括一个或更多个将NiV F胞外域三聚体稳定为融合前构象的氨基酸取代或缺失。

在一些实施方式中，重组NiV F胞外域三聚体的原聚体包括NiV F 104位和114位的半胱氨酸取代，其形成非天然原聚体内二硫键，用于以融合前构象稳定。

在一些实施方式中，重组NiV F胞外域三聚体的原聚体包括形成非天然原聚体内二硫键的NiV F 104位和114位半胱氨酸取代，以及NiV F 191位的脯氨酸取代，用于以融合前构象稳定。

在一些实施方式中，重组NiV F胞外域三聚体的原聚体包括形成非天然原聚体内二硫键的NiV F 104位和114位半胱氨酸取代，以及NiV F 172位的苯丙氨酸取代，用于以融合前构象稳定。

在一些实施方式中，重组NiV F胞外域三聚体的原聚体包括形成非天然原聚体内二硫键的NiV F 104位和114位半胱氨酸取代，以及NiV F 70位的甘氨酸取代，用于以融合前构象稳定。

在一些实施方式中，重组NiV F胞外域三聚体的原聚体包括形成非天然原聚体内二硫键的NiV F 104位和114位半胱氨酸取代、NiV F 191位的脯氨酸取代以及NiV F172位的苯丙氨酸取代，用于以融合前构象稳定。

在一些实施方式中，重组NiV F胞外域三聚体的原聚体包括形成非天然原聚体内二硫键的NiV F 104位和114位半胱氨酸取代、NiV F 172位的苯丙氨酸取代以及NiV F 70位的甘氨酸取代，用于以融合前构象稳定。

在一些实施方式中，重组NiV F胞外域三聚体的原聚体包括形成非天然原聚体内二硫键的NiV F 104位和114位半胱氨酸取代、NiV F 191位的脯氨酸取代以及NiV F70位的甘氨酸取代，用于以融合前构象稳定。

在一些实施方式中，重组NiV F胞外域三聚体的原聚体包括形成非天然原聚体内二硫键的NiV F 104位和114位半胱氨酸取代、NiV F 191位的脯氨酸取代、NiV F 172位的苯丙氨酸取代以及NiV F 70位的甘氨酸取代，用于以融合前构象稳定。

在一些实施方式中，重组NiV F胞外域三聚体的原聚体包括形成非天然原聚体内二硫键的NiV F 114位和426位的半胱氨酸取代，用于以融合前构象稳定。

在一些实施方式中，重组NiV F胞外域三聚体的原聚体包括形成非天然原聚体内二硫键的NiV F 114位和426位的半胱氨酸取代，以及NiV F 191位的脯氨酸取代，用于以融合前构象稳定。

在一些实施方式中，重组NiV F胞外域三聚体的原聚体包括形成非天然原聚体内二硫键的NiV F 114位和426位的半胱氨酸取代，以及NiV F 172位的苯丙氨酸取代，用于以融合前构象稳定。

在一些实施方式中，重组NiV F胞外域三聚体的原聚体包括形成非天然原聚体内二硫键的NiV F 114位和426位的半胱氨酸取代，以及NiV F 70位的甘氨酸取代，用于以融合前构象稳定。

在一些实施方式中，重组NiV F胞外域三聚体的原聚体包括形成非天然原聚体内二硫键的NiV F 114位和426位的半胱氨酸取代、NiV F 191位的脯氨酸取代以及NiV F 172位的苯丙氨酸取代，用于以融合前构象稳定。

在一些实施方式中，重组NiV F胞外域三聚体的原聚体包括形成非天然原聚体内二硫键的NiV F 114位和426位的半胱氨酸取代、NiV F 172位的苯丙氨酸取代以及NiV F70位的甘氨酸取代，用于以融合前构象稳定。

在一些实施方式中，重组NiV F胞外域三聚体的原聚体包括形成非天然原聚体内二硫键的NiV F 114位和426位的半胱氨酸取代、NiV F 191位的脯氨酸取代以及NiV F 70位的甘氨酸取代，用于以融合前构象稳定。

在一些实施方式中，重组NiV F胞外域三聚体的原聚体包括形成非天然原聚体内二硫键的NiV F 114位和426位的半胱氨酸取代、NiV F 191位的脯氨酸取代、NiV F 172位的苯丙氨酸取代以及NiV F 70位的甘氨酸取代，用于以融合前构象稳定。

在一些实施方式中，重组NiV F胞外域三聚体的原聚体包括NiV F 191位的脯氨酸取代，用于以融合前构象稳定。

在一些实施方式中，重组NiV F胞外域三聚体的原聚体包括NiV F 172位的苯丙氨酸取代，用于以融合前构象稳定。

在一些实施方式中，重组NiV F胞外域三聚体的原聚体包括NiV F 70位的甘氨酸取代，用于以融合前构象稳定。

在一些实施方式中，重组NiV F胞外域三聚体的原聚体包括NiV F 191位的脯氨酸取代，以及NiV F 172位的苯丙氨酸取代，用于以融合前构象稳定。

在一些实施方式中，重组NiV F胞外域三聚体的原聚体包括NiV F 191位的脯氨酸取代，以及NiV F 70位的甘氨酸取代，用于以融合前构象稳定。

在一些实施方式中，重组NiV F胞外域三聚体的原聚体包括NiV F 172位的苯丙氨酸取代，以及NiV F 70位的甘氨酸取代，用于以融合前构象稳定。

在一些实施方式中，重组NiV F胞外域三聚体的原聚体包括NiV F 191位的脯氨酸取代、NiV F 172位的苯丙氨酸取代以及NiV F 70位的甘氨酸取代，用于以融合前构象稳定。

上述任何重组NiV F蛋白可进一步包括修饰，以消除F1和F2多肽之间的蛋白酶切割位点，从而产生“单链”重组F蛋白。例如，除了上面列出的在102-113位内包括修饰的变体，上述任何重组NiV蛋白均可以包括NiV F 102-113位的缺失，其中101位和114位通过甘氨酸-丝氨酸接头连接

对于以上列出的实施方式，特定氨基酸取代的非限制性实例包括：NiV F 104和114位的半胱氨酸取代是L104C和I114C取代；NiV F 114位和426位的半胱氨酸取代是I114C和I426C取代；NiV F 191位的脯氨酸取代是S191P取代；NiV F 172位的苯丙氨酸取代是L172F取代；NiV F 70位的甘氨酸取代是Q70G取代；和(HDLVGDVRLAGV)102-113(GSG)取代，用于NiV F 102-113位的缺失，其中101位和114位通过甘氨酸-丝氨酸接头连接。

在几个实施方式中，重组NiV F胞外域的原聚体可以包括一个或更多个另外的氨基酸取代，例如，以增加融合前构象的稳定性，或用于其他目的，诸如增加溶解度或减少不必要的免疫应答。

以上列出的非天然二硫键在其融合前构象中稳定了NiV F胞外域的膜远端部分。这些突变中的任何一个都可以与对NiV F胞外域的膜近端部分(诸如茎)的修饰相结合，例如，以增加胞外域的三聚化。

在几个实施方式中，原聚体中重组F2肽的N端位置可以是NiV F 20-30位中的一个(诸如25位)，并且F1胞外域的C端位置可以来自胞外域的茎区域，诸如NiV F 475-495位中的一个(诸如480-490位，例如488位)。

提供了NiV F胞外域三聚体的原聚体的非限制性实例，包括用于以融合前构象稳定的氨基酸取代以及与三聚结构域的C端连接，如SEQ ID NO:5、7-7、11-18、20-21、23-24和26-32中任一个的残基21-486，以及SEQ ID NO:19、22和25中任一个的残基21-477。在一些实施方式中，NiV F胞外域三聚体的原聚体包括与SEQ ID NO:5、7-7、11-18、20-21、23-24和26-32中任一个的残基21-486，或SEQ ID NO:19、22和25中任一个的残基21-477具有至少90％同一性的氨基酸序列；其中原聚体包括一个或更多个将NiV F胞外域三聚体稳定为融合前构象的氨基酸取代。在一些实施方式中，NiV F胞外域三聚体的原聚体包括SEQ ID NO:5、7-7、11-18、20-21、23-24和26-32中任一个的残基21-486，或SEQ ID NO:19、22和25中任一个的残基21-477。

在几个实施方式中，重组NiV F胞外域三聚体是可溶性蛋白复合物，例如，用作重组亚基疫苗。在几个这样的实施方式中，重组NiV F胞外域三聚体的原聚体可以各自包括与三聚结构域诸如GCN4三聚结构域或T4纤维蛋白三聚结构域的C端连接。三聚结构域促进重组NiV F胞外域三聚体的膜近端方面的三聚化和稳定。例如，重组NiV F胞外域三聚体的原聚体的C端残基(诸如三聚体的茎区域的残基)可以直接连接至三聚结构域，或经由肽接头间接连接至三聚结构域。示例性接头包括甘氨酸和甘氨酸-丝氨酸接头。促进可溶性重组蛋白稳定三聚体的外源多聚结构域的非限制性实例包括：GCN4亮氨酸拉链、T4纤维蛋白三聚结构域、来自肺表面活性剂蛋白的三聚基序(Hoppe et al.1994FEBS Lett 344:191-195)或胶原蛋白(McAlinden et al.2003J Biol Chem 278:42200-42207)，它们中的任何一个均可以与重组NiV F胞外域的原聚体的C端连接以促进三聚化，只要重组NiV F胞外域三聚体保留了融合前构象。在一些实例中，重组NiV F胞外域三聚体的原聚体可以与NiV三聚结构域连接，例如，该三聚体中的每个原聚体可以包括与GCN4三聚结构域的C端连接，诸如与NiV F 470-490位中任一位置连接，诸如NiV F 488位。在特定实例中，GCN4纤维蛋白三聚结构域可以包括氨基酸序列IEDKIEEILSKIYHIENEIARIKKLIGEAP(NiV01的残基490-519，SEQID NO:1)。

提供了NiV F胞外域三聚体的原聚体的非限制性实例，包括用于以融合前构象稳定的氨基酸取代以及与三聚结构域的C端连接如，SEQ ID NO:5、7-7、11-18、20-21、23-24和26-32中任一个的残基21-519，以及SEQ ID NO:19、22和25中任一个的残基21-510。在一些实施方式中，NiV F胞外域三聚体的原聚体包括与SEQ ID NO:5、7-7、11-18、20-21、23-24和26-32中任一个的残基21-519，或SEQ ID NO:19、22和25中任一个的残基21-510具有至少90％同一性的氨基酸序列；其中原聚体包括一个或更多个将NiV F胞外域三聚体稳定为融合前构象的的氨基酸取代。在一些实施方式中，NiV F胞外域三聚体的原聚体包括SEQ IDNO:5、7-7、11-18、20-21、23-24和26-32中任一个的残基21-519，或SEQ ID NO:19、22和25中任一个的残基21-510。

在一些实施方式中，重组NiV F胞外域三聚体可以是膜锚定的蛋白复合物，例如用于减毒病毒或病毒样颗粒疫苗。膜锚定可以例如通过将重组NiV F胞外域三聚体的原聚体与跨膜结构域和任选的细胞质尾(诸如NiV F跨膜结构域和胞质尾)的C端连接来完成。在一些实施方式中，一个或更多个肽接头(诸如gly-ser接头，例如10个氨基酸的甘氨酸-丝氨酸肽接头)可用于将重组NiV F胞外域三聚体的原聚体连接至跨膜结构域。与公开的实施方式一起使用的跨膜结构域的非限制性实例包括NiV F跨膜结构域，诸如ILYVLSIASLCIGLITFISFIIV(SEQ ID NO:52的残基496-518)。

来自不同NiV株的天然NiV F蛋白以及编码此类蛋白和方法的核酸序列是已知的，并且可以使用本文提供的描述进行改变以产生重组NiV F胞外域三聚体。

B.与异源部分连接的NiV F胞外域三聚体

重组NiV F胞外域可以被衍生化或连接至另一分子(诸如另一肽或蛋白)。通常，重组NiV F胞外域经衍生化使得广泛中和抗体与重组NiV F蛋白三聚体的结合不受衍生或标记的不利影响。例如，重组NiV F胞外域可以功能性地连接(通过化学偶联、遗传融合、非共价结合或其他方式)至一种或更多种其他分子实体，诸如抗体或蛋白或检测标签。

在一些实施方式中，重组NiV F胞外域三聚体与NiV G胞外域融合(诸如SEQ IDNO:53或54所示的G序列的胞外域)。例如，重组NiV F胞外域三聚体的原聚体分别与NiV G蛋白胞外域融合。融合可以是直接的或通过肽接头。在一些实施方式中，NiV G胞外域可直接或通过肽接头间接地融合至NiV F胞外域三聚体的原聚体的N端。在一些实施方式中，可以将NiV G胞外域直接或经由肽接头间接融合至NiV F胞外域三聚体的原聚体的C端。在一些这样的实施方式中，NiV G胞外域可直接或经由肽接头间接融合至融合至NiV F胞外域三聚体的原聚体的C端的三聚结构域的C端(诸如GCN4或T4纤维蛋白三聚结构域)。在一些这样的实施方式中，连接至三聚结构域和NiV G胞外域的NiV F胞外域三聚体的原聚体包括以下所示的氨基酸序列：SEQ ID NO:43(NiVop08–TD(GCN4-Fd)-G)的残基21-981或SEQ ID NO:44(G–NiVop08-TD(GCN4-Fd))的残基27-981、SEQ ID NO:59(NiVop08-GCN4-G)的残基21-952、或SEQ ID NO:60(NiVop08-Fd-G)的残基21-946，或者与SEQ ID NO:43(NiVop08–TD(GCN4-Fd)-G)的残基21-981、SEQ ID NO:44(G–NiVop08-TD(GCN4-Fd))的残基27-981、SEQ ID NO:59(NiVop08-GCN4-G)的残基21-952、或SEQ ID NO:60(NiVop08-Fd-G)的残基21-946具有至少90％同一性的氨基酸序列。

在一些实施方式中，多于一个(诸如2、3或4个)NiV G胞外域与NiV F三聚体的原聚体融合。例如，可以将第一NiV G胞外域直接或经由肽接头间接融合到NiV F胞外域三聚体的原聚体的N端，并且可以将第二NiV G胞外域直接或经由肽接头间接融合至NiV F胞外域三聚体的原聚体的C端(或融合至融合至NiV F胞外域三聚体的原聚体的C端的三聚结构域(诸如GCN4或T4纤维蛋白三聚体域)的C端))。

在一些实施方式中，将重组NiV F胞外域三聚体与来自异源性亨尼帕病毒(诸如Hendra病毒(HeV)、Cedar病毒(CedV)、Kumasi病毒(KV)、Hendra病毒(HeV)、或Mòjiāng病毒(MojV)的G蛋白的胞外域融合。例如，将重组的NiV F胞外域三聚体与包括如下序列的HeV G胞外域融合：

HeV G胞外域(SEQ ID NO:68，来自GenBank:AEB21225.1)：

REYRPISQGVSDLVGLPNQICLQKTTSTILKPRLISYTLPINTREGVCITDPLLAVDNGFFAYSHLEKIGSCTRGIAKQRIIGVGEVLDRGDKVPSMFMTNVWTPPNPSTIHHCSSTYHEDFYYTLCAVSHVGDPILNSTSWTESLSLIRLAVRPKSDSGDYNQKYIAITKVERGKYDKVMPYGPSGIKQGDTLYFPAVGFLPRTEFQYNDSNCPIIHCKYSKAENCRLSMGVNSKSHYILRSGLLKYNLSLGGDITLQFIEIADNRLTIGSPSKIYNSLGQPVFYQASYSWDTMIKLGDVDTVDPLRVQWRNNSVISRPGQSQCPRFNVCPEVCWEGTYNDAFLIDRLNWVSAGVYLNSNQTAENPVFAVFKDNEILYQVPLAEDDTNAQKTITDCFLLENVIWCISLVEIYDTGDSVIRPKLFAVKIPAQCSES

在一些这样的实施方式中，重组NiV F胞外域三聚体的原聚体各自融合至来自亨尼帕病毒的G蛋白的胞外域，诸如HeV G胞外域。融合可以是直接的或通过肽接头。在一些实施方式中，来自亨尼帕病毒的G蛋白的胞外域(诸如HeV G胞外域)可以直接或通过肽接头间接融合至NiV F胞外域三聚体的原聚体的N端。在一些实施方式中，来自亨尼帕病毒的G蛋白的胞外域(诸如HeV G胞外域)可以直接或经由肽接头间接融合至NiV F胞外域三聚体的原聚体的C端。在一些这样的实施方式中，来自亨尼帕病毒的G蛋白的胞外域(诸如HeV G胞外域)可以直接或经由肽接头间接融合至融合至NiV F胞外域三聚体的原聚体的C端的三聚结构域的C端(诸如GCN4或T4纤维蛋白三聚结构域)。在一些这样的实施方式中，与三聚结构域和来自亨尼帕病毒的G蛋白的胞外域(诸如HeV G胞外域)连接的NiV F胞外域三聚体的原聚体包含如下氨基酸序列：

NiVop8-HeV G(SEQ ID NO:69):

mysmqlascvtltlvllvnsQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSQCTGSVMENYKTRLNGILTPIKGALEIYKNNTHDCVGDVRLAGVCMAGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVFTALQDYINTNLVPTIDKIPCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLKLMKQIEDKIEEILSKIYHIENEIARIKKLIGEAPGSGYIPEAPRDGQAYVRKDGEWVLLSTFLGSGGGGGGVSDLVGLPNQICLQKTTSTILKPRLISYTLPINTREGVCITDPLLAVDNGFFAYSHLEKIGSCTRGIAKQRIIGVGEVLDRGDKVPSMFMTNVWTPPNPSTIHHCSSTYHEDFYYTLCAVSHVGDPILNSTSWTESLSLIRLAVRPKSDSGDYNQKYIAITKVERGKYDKVMPYGPSGIKQGDTLYFPAVGFLPRTEFQYNDSNCPIIHCKYSKAENCRLSMGVNSKSHYILRSGLLKYNLSLGGDITLQFIEIADNRLTIGSPSKIYNSLGQPVFYQASYSWDTMIKLGDVDTVDPLRVQWRNNSVISRPGQSQCPRFNVCPEVCWEGTYNDAFLIDRLNWVSAGVYLNSNQTAENPVFAVFKDNEILYQVPLAEDDTNAQKTITDCFLLENVIWCISLVEIYDTGDSVIRPKLFAVKIPAQCSESgglvprgshhhhhhsawshpqfek

HeV G-NiVop8(SEQ ID NO:70):

mysmqlascvtltlvllvnsqrpqtegvsnlvglpnniclqktsnqilkpklisytlpvvgqsgtcitdpllamdegyfayshlerigscsrgvskqriigvgevldrgdevpslfmtnvwtppnpntvyhcsavynnefyyvlcavstvgdpilnstywsgslmmtrlavkpksngggynqhqlalrsiekgrydkvmpygpsgikqgdtlyfpavgflvrtefkyndsncpitkcqyskpencrlsmgirpnshyilrsgllkynlsdgenpkvvfieisdqrlsigspskiydslgqpvfyqasfswdtmikfgdvltvnplvvnwrnntvisrpgqsqcprfntcpeicwegvyndaflidrinwisagvfldsnqtaenpvftvfkdneilyraqlasedtnaqktitncfllknkiwcislveiydtgdnvirpklfavkipeqctgggQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSQCTGSVMENYKTRLNGILTPIKGALEIYKNNTHDCVGDVRLAGVCMAGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVFTALQDYINTNLVPTIDKIPCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLKLMKQIEDKIEEILSKIYHIENEIARIKKLIGEAPGSGYIPEAPRDGQAYVRKDGEWVLLSTFLGSLVPRGSHHHHHHSAWSHPQFEK

以上序列包括N端信号肽、NiV F胞外域(NiVop8)、HeV G胞外域、GCN4三聚结构域、T4-纤维蛋白三聚结构域、凝血酶裂解位点、HIS标签和Strep标签，以及区段之间的各种接头残基。这些蛋白的纯化形式通常缺少N端信号肽和通过凝血酶裂解去除的C端残基。

在一些实施方式中，多于一个(诸如2、3或4个)来自亨尼帕病毒的G蛋白的胞外域(诸如HeV G胞外域)与NiV F三聚体的原聚体融合。例如，首先可以将来自亨尼帕病毒的G蛋白的胞外域(诸如HeV G胞外域)直接或通过肽接头间接融合至NiV F胞外域三聚体的原聚体的N端，其次，可以将来自亨尼帕病毒的G蛋白的胞外域(诸如HeV G胞外域)直接或通过肽接头间接融合至NiV F胞外域三聚体的原聚体的C端(或融合至融合至NiV F胞外域三聚体的原聚体的C端的三聚结构域的C端(诸如GCN4或T4纤维蛋白三聚结构域))。

C.包括三聚结构域的NiV G多聚体

在一些实施方式中，提供了包括NiV G胞外域的多聚体的免疫原。在一些实施方式中，免疫原包括融合蛋白的三聚体，每个融合蛋白包括一个或更多个NiV G胞外域和三聚结构域(例如GCN4三聚结构域、T4纤维蛋白三聚结构域或与T4纤维蛋白三聚结构域融合的GCN4三聚结构域)。在一些实施方式中，融合蛋白在N端至C端方向上包括一个或更多个(诸如一个、两个或三个)NiV G胞外域和三聚结构域。在一些实施方式中，融合蛋白在N端至C端方向上包括三聚结构域和一个或更多个(例如一个、两个或三个)NiV G胞外域。在一些实施方式中，融合蛋白在N端至C端方向上包括一个或更多个(例如一个、两个或三个)NiV G胞外域、三聚结构域和一个或更多个(例如一个、两个或三个)NiV G胞外域。三聚结构域相互作用形成三聚体。在一些实施方式中，三聚体中的融合蛋白包括如下所示的氨基酸序列或由其组成：SEQ ID NO:34的残基21-463、SEQ ID NO:35的残基21-895、SEQ ID NO:36的残基21-1327、SEQ ID NO:37的残基23-912，或者与SEQ ID NO:34的残基21-463、SEQ ID NO:35的残基21-895、SEQ ID NO:36的残基21-1327、SEQ ID NO:37的残基23-912中任一个具有至少90％同一性的序列。

D.附加说明

重组NiV F胞外域三聚体中的原聚体除了上述，还可以包含天然NiV F序列的修饰，诸如氨基酸取代、缺失或插入、糖基化和/或与不相关蛋白(例如，蛋白标签)的共价连接)，只要重组NiV F胞外域三聚体以融合前构象保持稳定并保持免疫原性即可。此外，NiVG胞外域多聚体中的融合蛋白可以包括对天然NiV G序列的修饰，诸如氨基酸取代、缺失或插入、糖基化和/或与无关蛋白(例如，蛋白标签)的共价连接，只要NiV G胞外域保持免疫原性。这些序列上的变化可以是天然发生的变化，或者可以通过使用本领域技术人员已知的基因工程技术进行工程化。这些技术的实例可见于，例如，Sambrook et al.(MolecularCloning:A Laboratory Manual,4

在一些实施方式中，与相应的天然NiV F或G序列相比，重组NiV F胞外域三聚体或NiV G多聚体中的原聚体可以包括一个或更多个氨基酸取代。例如，在一些实施方式中，与天然NiV F或G序列相比，F

在一些实施方式中，重组NiV F胞外域三聚体或NiV G多聚体中的原聚体可以在任一末端与其他无关序列(例如非NiV F或G蛋白序列、非病毒包膜或非病毒蛋白序列)连接

在一些实施方式中，重组NiV F胞外域三聚体或NiV G多聚体可溶于水溶液。在一些实施方式中，重组NiV F胞外域三聚体或NiV G多聚体在水溶液(诸如磷酸盐缓冲液(pH7.4)或350mM NaCl(pH 7.0))中在室温(诸如20-22摄氏度)下溶解至少0.5mg/ml(诸如至少1.0mg/ml、1.5mg/ml、2.0mg/ml、3.0mg/ml、4.0mg/ml或至少5.0mg/ml)并保持溶解状态至少12小时(例如至少24小时、至少48小时、至少1周、至少2周、至少1个月或更长时间)。在一个实施方式中，磷酸盐缓冲液包括pH7.4的NaCl(137mM)、KCl(2.7mM)、Na

在一些实施方式中，重组NiV F胞外域三聚体可以作为可溶性三聚体的均质群体提供，其不包括可检测的为融合后构象的NiV F胞外域三聚体。NiV F胞外域三聚体的构象可以例如通过负染色电子显微镜和/或通过适当的融合前或融合后特异性抗体进行特异性结合来检测。在一些实施方式中，均质群体中至少约95％的重组NiV F胞外域三聚体(例如至少约95％、96％、97％、98％、99％或99.9％的NiV F蛋白)以融合前构象稳定。

在一些实施方式中，重组NiV F胞外域三聚体在磷酸盐缓冲液中在50℃下孵育1小时后，保留与融合前特异性抗体的特异性结合。在一些实施方式中，重组NiV F胞外域三聚体在磷酸盐缓冲液中于4℃下孵育六个月后，保留与融合前特异性抗体的特异性结合。

在某些实施方式中，本文提供的免疫原可以被进一步修饰以包含本领域已知且容易获得的其他非蛋白部分。适合于免疫原衍生化的部分包括但不限于水溶性聚合物。水溶性聚合物的非限制性实例包括但不限于聚乙二醇(PEG)、乙二醇/丙二醇共聚物、羧甲基纤维素、葡聚糖、聚乙烯醇、聚乙烯吡咯烷酮、聚-1,3-二氧戊环、聚-1,3,6-三恶烷、乙烯/马来酸酐共聚物、聚氨基酸(均聚物或无规共聚物)以及右旋糖酐或聚(正乙烯基吡咯烷酮)聚乙烯二醇、丙二醇均聚物、环氧丙烷/环氧乙烷共聚物、聚氧乙烯化多元醇(例如甘油)、聚乙烯醇及其混合物。聚乙二醇丙醛由于在水中具有稳定性而在生产中可能具有优势。该聚合物可以具有任何分子量，并且可以是支链或直链的。附着至抗体的聚合物的数量可以变化，并且如果附着的聚合物多于一种，则它们可以是相同或不同的分子。通常，用于衍生化的聚合物的数量和/或类型可以基于以下考虑因素来确定，这些考虑因素包括但不限于待改善或改变的免疫原的特定性质或功能，免疫原衍生物是否会在指定情况下用于治疗等。

本文提供的包括重组NiV F或G胞外域的一些序列包括蛋白酶切割位点(诸如凝血酶位点)、蛋白标签(诸如His标签、Strep标签II、Avi标签等)的序列，以及信号肽；可以从分离的免疫原中除去此类序列，该分离的免疫原包括重组的NiV F或G胞外域三聚体，以用于治疗用途。

E.蛋白纳米颗粒

在一些实施方式中，提供了蛋白纳米颗粒，其包括一个或更多个公开的重组NiV F胞外域三聚体或NiV G胞外域。纳米颗粒的非限制性实例包括铁蛋白纳米颗粒、囊包蛋白纳米颗粒、硫氧化酶还原酶(SOR)纳米颗粒和二氧四氢蝶啶合酶纳米颗粒，其分别由单体亚基的组装组成，该单体亚基包括铁蛋白蛋白、囊包蛋白、SOR蛋白和二氧四氢蝶啶合酶。为了构建这样的蛋白纳米颗粒，可以将NiV F胞外域三聚体的原聚体与蛋白纳米颗粒的亚基(如铁蛋白、囊包蛋白、SOR或二氧四氢蝶啶合酶蛋白)连接，并在适当的条件下在细胞中表达。融合蛋白可自组装成纳米颗粒，任何均可纯化。

在一些实施方式中，可以将公开的重组NiV F胞外域三聚体的原聚体或NiV G胞外域与铁蛋白亚基连接以构建铁蛋白纳米颗粒。铁蛋白纳米颗粒及其在免疫目的(例如，针对流感抗原的免疫中)的用途已在本领域中公开(参见，例如，Kanekiyo et al.,Nature,499:102-106,2013，通过引用以其全文并入本文)。铁蛋白纳米颗粒的球形形式由单体亚基组成，该单体亚基是分子量约为17-20kDa的多肽。产生后，这些单体亚基蛋白自组装成球状铁蛋白蛋白。因此，铁蛋白的球状形式包括24个单体亚基蛋白，并具有具有432对称性的衣壳样结构。本文进一步描述了构建铁蛋白纳米颗粒的方法(参见，例如，Zhang,Int.J.Mol.Sci.,12:5406-5421,2011，其通过引用以其全文并入本文)。一种这样的单体铁蛋白亚基的氨基酸序列的实例如下所示：

DIIKLLNEQVNKEMQSSNLYMSMSSWCYTHSLDGAGLFLFDHAAEEYEHAKKLIIFLNENNVPVQLTSISAPEHKFEGLTQIFQKAYEHEQHISESINNIVDHAIKSKDHATFNFLQWYVAEQHEEEVLFKDILDKIELIGNENHGLYLADQYVKGIAKSRKS(SEQ ID NO:55)

在特定实例中，铁蛋白多肽是大肠杆菌铁蛋白、幽门螺杆菌铁蛋白、人轻链铁蛋白、牛蛙铁蛋白或其杂交物，诸如大肠杆菌-人杂铁蛋白、大肠杆菌-牛蛙杂交铁蛋白或人-牛蛙杂交铁蛋白。铁蛋白多肽的示例性氨基酸序列和用于编码包括重组NiV F胞外域三聚体的铁蛋白纳米颗粒的编码铁蛋白多肽的核酸序列可见

在一些实施方式中，形成铁蛋白纳米颗粒的自组装融合蛋白包括任一如下所示的氨基酸序列或由其组成：SEQ ID NO:38的残基57-652、SEQ ID NO:39的残基57-661、SEQ IDNO:40的残基57-671、SEQ ID NO:41的残基57-681，或者与SEQ ID NO:38的残基57-652、SEQID NO:39的残基57-661、SEQ ID NO:40的残基57-671、SEQ ID NO:41的残基57-681具有至少90％同一性的序列。

在一些实施方式中，可以将公开的重组NiV F胞外域三聚体的原聚体或NiV G胞外域连接至二氧四氢蝶啶合酶亚基以构建二氧四氢蝶啶合酶纳米颗粒。二氧四氢蝶啶合酶纳米颗粒的球状形式由单体亚基组成。提供一种这样的二氧四氢蝶啶合酶亚基的序列的实例，其氨基酸序列如下所示：

MQIYEGKLTAEGLRFGIVASRFNHALVDRLVEGAIDCIVRHGGREEDITLVRVPGSWEIPVAAGELARKEDIDAVIAIGVLIRGATPHFDYIASEVSKGLADLSLELRKPITFGVITADTLEQAIERAGTKHGNKGWEAALSAIEMANLFKSLR(SEQ ID NO:56)。

在一些实施方式中，可以将公开的重组NiV F胞外域三聚体或NiV G胞外域的原聚体连接至二氧四氢蝶啶合酶亚基，其包括与SEQ ID NO:56所示的氨基酸序列具有至少80％(诸如至少85％、至少90％、至少95％或至少97％)同一性的氨基酸序列。

在一些实施方式中，形成二氧四氢蝶啶合酶纳米颗粒的自组装融合蛋白包括任一如下所示的氨基酸序列或由其组成：SEQ ID NO:42的残基57-647或与SEQ ID NO:42的残基57-647中任一个具有至少90％同一性的序列。

在一些实施方式中，可以将公开的重组NiV F胞外域三聚体的原聚体或NiV G胞外域连接至囊包蛋白纳米颗粒亚基以构建囊包蛋白纳米颗粒。囊包蛋白纳米颗粒的球状形式由单体亚基组成。一个这样的囊包蛋白亚基的序列的实例提供为如下所示的氨基酸序列

MEFLKRSFAPLTEKQWQEIDNRAREIFKTQLYGRKFVDVEGPYGWEYAAHPLGEVEVLSDENEVVKWGLRKSLPLIELRATFTLDLWELDNLERGKPNVDLSSLEETVRKVAEFEDEVIFRGCEKSGVKGLLSFEERKIECGSTPKDLLEAIVRALSIFSKDGIEGPYTLVINTDRWINFLKEEAGHYPLEKRVEECLRGGKIITTPRIEDALVVSERGGDFKLILGQDLSIGYEDREKDAVRLFITETFTFQVVNPEALILLKF(SEQ ID NO:57).

在一些实施方式中，公开的重组NiV F胞外域三聚体的原聚体或NiV G胞外域可以与囊包蛋白亚基连接，该囊包蛋白包括与SEQ ID NO:57所示氨基酸序列具有至少80％(诸如至少85％、至少90％、至少95％或至少97％)同一性的氨基酸序列。

囊包蛋白是细菌蛋白的保守家族，也被称为亚麻蛋白酶样蛋白，其形成大蛋白组装体，充当包装酶的最小区室。囊包蛋白组装体由单体亚基组成，该单体亚基是分子量约为30kDa的多肽。产生后，该单体亚基自组装成球状囊包蛋白组件，其中包括60个或在某些情况下为180个单体亚基。进一步描述了构建囊包蛋白纳米颗粒的方法(参见，例如，Sutteret al.,Nature Struct.and Mol.Biol.,15:939-947,2008，其通过引用以其全文并入本文)。在特定的实例中，囊包蛋白多肽是细菌囊包蛋白，诸如海栖热袍菌(Thermotogamaritime)或激烈火球菌(Pyrococcus furiosus)或红串红球菌(Rhodococcuserythropolis)或黄腐粘球菌(Myxococcus xanthus)囊包蛋白。

在一些实施方式中，可以将公开的重组NiV F胞外域三聚体或NiV G胞外域的原聚体与硫氧合酶还原酶(SOR)亚基连接以构建重组SOR纳米颗粒。在一些实施方式中，SOR亚基可包括如下所示的氨基酸序列

MEFLKRSFAPLTEKQWQEIDNRAREIFKTQLYGRKFVDVEGPYGWEYAAHPLGEVEVLSDENEVVKWGLRKSLPLIELRATFTLDLWELDNLERGKPNVDLSSLEETVRKVAEFEDEVIFRGCEKSGVKGLLSFEERKIECGSTPKDLLEAIVRALSIFSKDGIEGPYTLVINTDRWINFLKEEAGHYPLEKRVEECLRGGKIITTPRIEDALVVSERGGDFKLILGQDLSIGYEDREKDAVRLFITETFTFQVVNPEALILLKF(SEQ ID NO:58)。

在一些实施方式中，公开的重组NiV F胞外域三聚体的原聚体或NiV G胞外域可以与SOR亚基连接，该SOR亚基包括与SEQ ID NO:58所示的氨基酸序列具有至少80％(诸如至少85％、至少90％、至少95％或至少97％)同一性的氨基酸序列。

SOR蛋白是微生物蛋白(例如来自形成24个亚基蛋白装配体的嗜酸热古细菌(Acidianus ambivalens))。构建SOR纳米颗粒的方法描述于Urich et al.,Science,311:996-1000,2006，其通过引用以其全文并入本文。用于制备SOR纳米颗粒的SOR蛋白的氨基酸序列的实例如Urich et al.,Science,311:996-1000,2006所述，其通过引用以其全文并入本文。

出于生产目的，与纳米颗粒亚基连接的重组NiV F胞外域或NiV G胞外域可以包括在细胞加工过程中裂解的N端信号肽。例如，与蛋白纳米颗粒亚基连接的重组NiV F胞外域原聚体或NiV G胞外域可以在其N端包含信号肽，包括例如天然NiV F或G信号肽。

蛋白纳米颗粒可以在适当的细胞(例如，HEK 293Freestyle细胞)中表达，融合蛋白从自组装成纳米颗粒的细胞中分泌。可以使用已知技术，例如通过一些不同的色谱方法如Mono Q(阴离子交换)纯化纳米颗粒，然后进行体积排阻(

几个实施方式包括铁蛋白、囊包蛋白、SOR或二氧四氢蝶啶合酶蛋白的单体亚基，或其能够指导单体亚基自组装成球状形式蛋白的任何部分。来自任何已知铁蛋白、囊包蛋白、SOR或二氧四氢蝶啶合酶蛋白的单体亚基的氨基酸序列可用于产生具有重组NiV F胞外域或NiV G胞外域的融合蛋白，只要单体亚基能够自组装成在其表面上显示重组NiV F胞外域三聚体或NiV G胞外域的纳米颗粒。

融合蛋白不必包括铁蛋白、囊包蛋白、SOR或二氧四氢蝶啶合酶蛋白的单体亚基多肽的全长序列。可以使用单体亚基多肽的部分或区域，只要该部分包括指导单体亚基自组装成蛋白的球状形式的氨基酸序列。

II.多核苷酸及表达

还提供了编码任何公开的免疫原的多核苷酸。例如，编码以融合前构象稳定的NiVF胞外域三聚体的原聚体、重组NiV F胞外域三聚体和一个或更多个G胞外域的嵌合体、NiVG胞外域的多聚体、或含有重组NiV F或G胞外域的自组装蛋白纳米颗粒的亚基的多核苷酸。这些多核苷酸包括编码原聚体的DNA、cDNA和RNA序列。遗传密码可用于构建各种功能上等效的核酸，诸如序列不同但编码相同蛋白序列或编码包含该核酸序列的偶联物或融合蛋白的核酸。

在几个实施方式中，该核酸分子编码NiV F胞外域三聚体的原聚体的前体，当在适当的细胞中表达时，其被加工成F胞外域三聚体的原聚体，其可以自组装成相应的三聚体。例如，核酸分子可以编码NiV F胞外域三聚体的原聚体，其包括用于进入细胞分泌系统的N端信号序列，该N端信号序列在细胞中重组F胞外域的加工过程中被蛋白水解切割。

在一些实施方式中，核酸分子编码F

在一些实施方式中，该核酸分子编码全长F

示例性核酸序列包括：

NiVop08–TD(GCN4-Fd)-G(SEQ ID NO:61，其编码SEQ ID NO:43)

tctagagccaccatgtactctatgcagctggccagctgcgtgaccctgacactggtgctgctggtgaactctcagggcatcctgcactacgagaagctgagcaagatcggcctggtgaagggcgtgaccagaaagtataagatcaagtccaacccactgacaaaggacatcgtgatcaagatgatccccaacgtgagcaatatgtctcagtgtaccggctctgtgatggagaactacaagacccgcctgaatggcatcctgacaccaatcaagggcgccctggagatctataagaacaatacacacgactgcgtgggcgatgtgcggctggcaggcgtgtgcatggcaggagtggcaatcggaatcgcaaccgcagcacagatcacagcaggagtggccctgtatgaggccatgaagaacgccgacaacatcaataagctgaagagctccatcgagagcaccaatgaggccgtggtgaagctgcaggagacagccgagaagacagtgtacgtgttcacagccctgcaggactatatcaacaccaatctggtgcccacaatcgataagatcccctgcaagcagaccgagctgtccctggacctggccctgtctaagtacctgagcgatctgctgttcgtgtttggcccaaacctgcaggaccccgtgtccaattctatgacaatccaggccatctcccaggccttcggcggcaattacgagacactgctgagaacactgggctatgccaccgaggactttgacgatctgctggagagcgattccatcacaggccagatcatctatgtggatctgtctagctactatatcatcgtgagggtgtacttccctatcctgaccgagatccagcaggcctatatccaggagctgctgccagtgagcttcaacaatgacaattccgagtggatctctatcgtgcccaactttatcctggtgcggaacaccctgatcagcaatatcgagatcggcttttgcctgatcacaaagagatccgtgatctgtaatcaggactacgccacccccatgacaaacaatatgagggagtgcctgaccggctccacagagaagtgtccccgggagctggtggtgtcctctcacgtgcctagattcgccctgtccaacggcgtgctgtttgccaattgcatctctgtgacctgccagtgtcagaccacaggaagggcaatctctcagagcggagagcagaccctgctgatgatcgataacaccacatgtcctacagccgtgctgggcaatgtgatcatcagcctgggcaagtacctgggctccgtgaactataattctgagggaatcgcaatcggaccacccgtgttcaccgacaaggtggatatcagctcccagatctctagcatgaaccagagcctgcagcagtccaaggactacatcaaggaggcccagcggctgctggataccgtgaatccttctctgaagctgatgaagcagatcgaggataagatcgaggagatcctgagcaagatctatcacatcgagaacgagatcgccaggatcaagaagctgatcggagaggcacctggatctggttacatcccagaggctccgcgggatggacaggcctacgtgagaaaggacggcgagtgggtgctgctgagcaccttcctgggaagcggtggaggaggcggaggcgtgagcaatctggtgggcctgcccaacaatatctgtctgcagaagacctccaaccagatcctgaagcccaagctgatctcctatacactgcctgtggtgggccagtctggcacctgcatcacagaccctctgctggccatggatgagggctacttcgcctattctcacctggagaggatcggctcctgttctcgcggcgtgagcaagcagcggatcatcggagtgggagaggtgctggacaggggcgatgaggtgccttccctgttcatgaccaacgtgtggacaccacccaatccaaacaccgtgtaccactgctctgccgtgtataacaatgagttttactacgtgctgtgcgccgtgagcaccgtgggcgatcctatcctgaactccacatactggagcggctccctgatgatgaccagactggccgtgaagccaaagtccaatggcggcggctataaccagcaccagctggccctgagatctatcgagaagggcaggtacgataaagtgatgccttatggcccatctggcatcaagcagggcgacacactgtacttccccgccgtgggctttctggtgaggaccgagttcaagtacaatgactccaactgccctatcacaaagtgtcagtattctaagccagagaattgccgcctgagcatgggcatccggcccaactctcactacatcctgagaagcggcctgctgaagtataatctgagcgacggcgagaaccctaaggtggtgtttatcgagatctccgatcagaggctgtctatcggctctcccagcaagatctacgactccctgggccagcccgtgttctaccaggcctccttttcttgggacacaatgatcaagttcggcgatgtgctgaccgtgaatccactggtggtgaactggagaaacaataccgtgatcagcaggccaggacagtcccagtgtcctcgctttaacacatgcccagagatctgttgggagggcgtgtacaatgacgccttcctgatcgatcggatcaactggatctccgccggcgtgtttctggactctaatcagaccgccgagaaccccgtgttcacagtgtttaaggataatgagatcctgtacagggcacagctggcaagcgaggacaccaacgcccagaagaccatcacaaattgcttcctgctgaagaacaagatctggtgtatctccctggtggagatctatgacaccggcgataacgtgatccggccaaagctgtttgccgtgaagatccccgagcagtgcacaggcggcctggtgcctagaggctctcaccaccaccatcaccacagcgcctggtcccacccccagttcgagaagtgataggatcc

G–NiVop08-TD(GCN4-Fd)(SEQ ID NO:62，其编码SEQ ID NO:44)

tctagaccaccatgtactcaatgcagctggcctcttgcgtcacactgacactggtcctgctggtcaactcacagagaccacagaccgagggcgtgagcaatctggtgggcctgcccaacaatatctgtctgcagaagacctccaaccagatcctgaagcccaagctgatctcctatacactgcctgtggtgggccagtctggcacctgcatcacagaccctctgctggccatggatgagggctacttcgcctattctcacctggagaggatcggctcctgttctcgcggcgtgagcaagcagcggatcatcggagtgggagaggtgctggacaggggcgatgaggtgccttccctgttcatgaccaacgtgtggacaccacccaatccaaacaccgtgtaccactgctctgccgtgtataacaatgagttttactacgtgctgtgcgccgtgagcaccgtgggcgatcctatcctgaactccacatactggagcggctccctgatgatgaccagactggccgtgaagccaaagtccaatggcggcggctataaccagcaccagctggccctgagatctatcgagaagggcaggtacgataaagtgatgccttatggcccatctggcatcaagcagggcgacacactgtacttccccgccgtgggctttctggtgaggaccgagttcaagtacaatgactccaactgccctatcacaaagtgtcagtattctaagccagagaattgccgcctgagcatgggcatccggcccaactctcactacatcctgagaagcggcctgctgaagtataatctgagcgacggcgagaaccctaaggtggtgtttatcgagatctccgatcagaggctgtctatcggctctcccagcaagatctacgactccctgggccagcccgtgttctaccaggcctccttttcttgggacacaatgatcaagttcggcgatgtgctgaccgtgaatccactggtggtgaactggagaaacaataccgtgatcagcaggccaggacagtcccagtgtcctcgctttaacacatgcccagagatctgttgggagggcgtgtacaatgacgccttcctgatcgatcggatcaactggatctccgccggcgtgtttctggactctaatcagaccgccgagaaccccgtgttcacagtgtttaaggataatgagatcctgtacagggcacagctggcaagcgaggacaccaacgcccagaagaccatcacaaattgcttcctgctgaagaacaagatctggtgtatctccctggtggagatctatgacaccggcgataacgtgatccggccaaagctgtttgccgtgaagatccccgagcagtgcacaggcggcggtcagggcatcctgcactacgagaagctgagcaagatcggcctggtgaagggcgtgaccagaaagtataagatcaagtccaacccactgacaaaggacatcgtgatcaagatgatccccaacgtgagcaatatgtctcagtgtaccggctctgtgatggagaactacaagacccgcctgaatggcatcctgacaccaatcaagggcgccctggagatctataagaacaatacacacgactgcgtgggcgatgtgcggctggcaggcgtgtgcatggcaggagtggcaatcggaatcgcaaccgcagcacagatcacagcaggagtggccctgtatgaggccatgaagaacgccgacaacatcaataagctgaagagctccatcgagagcaccaatgaggccgtggtgaagctgcaggagacagccgagaagacagtgtacgtgttcacagccctgcaggactatatcaacaccaatctggtgcccacaatcgataagatcccctgcaagcagaccgagctgtccctggacctggccctgtctaagtacctgagcgatctgctgttcgtgtttggcccaaacctgcaggaccccgtgtccaattctatgacaatccaggccatctcccaggccttcggcggcaattacgagacactgctgagaacactgggctatgccaccgaggactttgacgatctgctggagagcgattccatcacaggccagatcatctatgtggatctgtctagctactatatcatcgtgagggtgtacttccctatcctgaccgagatccagcaggcctatatccaggagctgctgccagtgagcttcaacaatgacaattccgagtggatctctatcgtgcccaactttatcctggtgcggaacaccctgatcagcaatatcgagatcggcttttgcctgatcacaaagagatccgtgatctgtaatcaggactacgccacccccatgacaaacaatatgagggagtgcctgaccggctccacagagaagtgtccccgggagctggtggtgtcctctcacgtgcctagattcgccctgtccaacggcgtgctgtttgccaattgcatctctgtgacctgccagtgtcagaccacaggaagggcaatctctcagagcggagagcagaccctgctgatgatcgataacaccacatgtcctacagccgtgctgggcaatgtgatcatcagcctgggcaagtacctgggctccgtgaactataattctgagggaatcgcaatcggaccacccgtgttcaccgacaaggtggatatcagctcccagatctctagcatgaaccagagcctgcagcagtccaaggactacatcaaggaggcccagcggctgctggataccgtgaatccttctctgaagctgatgaagcagatcgaggataagatcgaggagatcctgagcaagatctatcacatcgagaacgagatcgccaggatcaagaagctgatcggagaggcacctggatctggttacatcccagaggctccgcgggatggacaggcctacgtgagaaaggacggcgagtgggtgctgctgagcaccttcctgggaagcctggtgcctaggggctcccaccaccaccaccaccacagcgcctggtcccacccacagtttgagaagtgatgaggatcc

NiV08(SEQ ID NO:63，其编码SEQ ID NO:24)

tctagagccaccatgtactctatgcagctggccagctgcgtgaccctgacactggtgctgctggtgaactctcagggcatcctgcactacgagaagctgagcaagatcggcctggtgaagggcgtgaccagaaagtataagatcaagtccaacccactgacaaaggacatcgtgatcaagatgatccccaacgtgagcaatatgtctcagtgtaccggctctgtgatggagaactacaagacccgcctgaatggcatcctgacaccaatcaagggcgccctggagatctataagaacaatacacacgactgcgtgggcgatgtgcggctggcaggcgtgtgcatggcaggagtggcaatcggaatcgcaaccgcagcacagatcacagcaggagtggccctgtatgaggccatgaagaacgccgacaacatcaataagctgaagagctccatcgagagcaccaatgaggccgtggtgaagctgcaggagacagccgagaagacagtgtacgtgttcacagccctgcaggactatatcaacaccaatctggtgcccacaatcgataagatcccctgcaagcagaccgagctgtccctggacctggccctgtctaagtacctgagcgatctgctgttcgtgtttggcccaaacctgcaggaccccgtgtccaattctatgacaatccaggccatctcccaggccttcggcggcaattacgagacactgctgagaacactgggctatgccaccgaggactttgacgatctgctggagagcgattccatcacaggccagatcatctatgtggatctgtctagctactatatcatcgtgagggtgtacttccctatcctgaccgagatccagcaggcctatatccaggagctgctgccagtgagcttcaacaatgacgattccgagtggatctctatcgtgcccaactttatcctggtgcggaacaccctgatcagcaatatcgagatcggcttttgcctgatcacaaagagatccgtgatctgtaatcaggactacgccacccccatgacaaacaatatgagggagtgcctgaccggctccacagagaagtgtccccgggagctggtggtgtcctctcacgtgcctagattcgccctgtccaacggcgtgctgtttgccaattgcatctctgtgacctgccagtgtcagaccacaggaagggcaatctctcagagcggagagcagaccctgctgatgatcgataacaccacatgtcctacagccgtgctgggcaatgtgatcatcagcctgggcaagtacctgggctccgtgaactataattctgagggaatcgcaatcggaccacccgtgttcaccgacaaggtggatatcagctcccagatctctagcatgaaccagagcctgcagcagtccaaggactacatcaaggaggcccagcggctgctggataccgtgaatccttctctgaagctgatgaagcagatcgaggataagatcgaggagatcctgagcaagatctatcacatcgagaacgagatcgccaggatcaagaagctgatcggagaggcacctggaggcctggtgccaaggggctcccaccaccaccaccaccacagcgcctggtcccacccacagtttgagaagtgatgaggatcc

G-ln5-Fer(SEQ ID NO:64，其编码SEQ ID NO:38)

tctagaccaccatgtactcaatgcagctggcctcttgcgtcacactgacactggtcctgctggtcaactcacagcaccaccaccatcatcacggaagcgcctggtcccaccctcagttcgagaagggaggactggtgcccagaggatccggcaacagccagcgccctcagaccgagggcgtgagcaatctggtgggcctgcccaacaatatctgtctgcagaagacctccaaccagatcctgaagcccaagctgatctcctatacactgcctgtggtgggccagtctggcacctgcatcacagaccctctgctggccatggatgagggctacttcgcctattctcacctggagaggatcggctcctgttctcgcggcgtgagcaagcagcggatcatcggagtgggagaggtgctggacaggggcgatgaggtgccttccctgttcatgaccaacgtgtggacaccacccaatccaaacaccgtgtaccactgctctgccgtgtataacaatgagttttactacgtgctgtgcgccgtgagcaccgtgggcgatcctatcctgaactccacatactggagcggctccctgatgatgaccagactggccgtgaagccaaagtccaatggcggcggctataaccagcaccagctggccctgagatctatcgagaagggcaggtacgataaagtgatgccttatggcccatctggcatcaagcagggcgacacactgtacttccccgccgtgggctttctggtgaggaccgagttcaagtacaatgactccaactgccctatcacaaagtgtcagtattctaagccagagaattgccgcctgagcatgggcatccggcccaactctcactacatcctgagaagcggcctgctgaagtataatctgagcgacggcgagaaccctaaggtggtgtttatcgagatctccgatcagaggctgtctatcggctctcccagcaagatctacgactccctgggccagcccgtgttctaccaggcctccttttcttgggacacaatgatcaagttcggcgatgtgctgaccgtgaatccactggtggtgaactggagaaacaataccgtgatcagcaggccaggacagtcccagtgtcctcgctttaacacatgcccagagatctgttgggagggcgtgtacaatgacgccttcctgatcgatcggatcaactggatctccgccggcgtgtttctggactctaatcagaccgccgagaaccccgtgttcacagtgtttaaggataatgagatcctgtacagggcacagctggcaagcgaggacaccaacgcccagaagaccatcacaaattgcttcctgctgaagaacaagatctggtgtatctccctggtggagatctatgacaccggcgataacgtgatccggccaaagctgtttgccgtgaagatccccgagcagtgcacaggcggcggcagcggcggggatatcattaagctgctgaacgaacaggtgaacaaggagatgcagtcaagcaacctgtacatgtctatgtcctcttggtgctatacacatagtctggacggagctggcctgttcctgtttgatcacgcagccgaggaatacgaacatgcaaagaaactgatcattttcctgaatgagaacaatgtgccagtccagctgacaagtatctcagcccccgaacacaagttcgaggggctgactcagatctttcagaaagcttacgaacacgagcagcatattagcgaatccatcaacaatattgtggaccacgctatcaagtccaaagatcatgcaaccttcaactttctgcagtggtacgtggccgagcagcacgaggaagaggtcctgtttaaggacatcctggataaaatcgaactgattggcaacgagaatcatgggctgtacctggccgatcagtatgtgaagggcattgctaagtcacggaaaagcggaagctgatgaccgcgg

NiVop08-GCN4-G(SEQ ID NO:65，其编码SEQ ID NO:59)

tctagagccaccatgtactctatgcagctggccagctgcgtgaccctgacactggtgctgctggtgaactctcagggcatcctgcactacgagaagctgagcaagatcggcctggtgaagggcgtgaccagaaagtataagatcaagtccaacccactgacaaaggacatcgtgatcaagatgatccccaacgtgagcaatatgtctcagtgtaccggctctgtgatggagaactacaagacccgcctgaatggcatcctgacaccaatcaagggcgccctggagatctataagaacaatacacacgactgcgtgggcgatgtgcggctggcaggcgtgtgcatggcaggagtggcaatcggaatcgcaaccgcagcacagatcacagcaggagtggccctgtatgaggccatgaagaacgccgacaacatcaataagctgaagagctccatcgagagcaccaatgaggccgtggtgaagctgcaggagacagccgagaagacagtgtacgtgttcacagccctgcaggactatatcaacaccaatctggtgcccacaatcgataagatcccctgcaagcagaccgagctgtccctggacctggccctgtctaagtacctgagcgatctgctgttcgtgtttggcccaaacctgcaggaccccgtgtccaattctatgacaatccaggccatctcccaggccttcggcggcaattacgagacactgctgagaacactgggctatgccaccgaggactttgacgatctgctggagagcgattccatcacaggccagatcatctatgtggatctgtctagctactatatcatcgtgagggtgtacttccctatcctgaccgagatccagcaggcctatatccaggagctgctgccagtgagcttcaacaatgacaattccgagtggatctctatcgtgcccaactttatcctggtgcggaacaccctgatcagcaatatcgagatcggcttttgcctgatcacaaagagatccgtgatctgtaatcaggactacgccacccccatgacaaacaatatgagggagtgcctgaccggctccacagagaagtgtccccgggagctggtggtgtcctctcacgtgcctagattcgccctgtccaacggcgtgctgtttgccaattgcatctctgtgacctgccagtgtcagaccacaggaagggcaatctctcagagcggagagcagaccctgctgatgatcgataacaccacatgtcctacagccgtgctgggcaatgtgatcatcagcctgggcaagtacctgggctccgtgaactataattctgagggaatcgcaatcggaccacccgtgttcaccgacaaggtggatatcagctcccagatctctagcatgaaccagagcctgcagcagtccaaggactacatcaaggaggcccagcggctgctggataccgtgaatccttctctgaagctgatgaagcagatcgaggataagatcgaggagatcctgagcaagatctatcacatcgagaacgagatcgccaggatcaagaagctgatcggagaggcacctggatctggtggaggaggcggaggcgtgagcaatctggtgggcctgcccaacaatatctgtctgcagaagacctccaaccagatcctgaagcccaagctgatctcctatacactgcctgtggtgggccagtctggcacctgcatcacagaccctctgctggccatggatgagggctacttcgcctattctcacctggagaggatcggctcctgttctcgcggcgtgagcaagcagcggatcatcggagtgggagaggtgctggacaggggcgatgaggtgccttccctgttcatgaccaacgtgtggacaccacccaatccaaacaccgtgtaccactgctctgccgtgtataacaatgagttttactacgtgctgtgcgccgtgagcaccgtgggcgatcctatcctgaactccacatactggagcggctccctgatgatgaccagactggccgtgaagccaaagtccaatggcggcggctataaccagcaccagctggccctgagatctatcgagaagggcaggtacgataaagtgatgccttatggcccatctggcatcaagcagggcgacacactgtacttccccgccgtgggctttctggtgaggaccgagttcaagtacaatgactccaactgccctatcacaaagtgtcagtattctaagccagagaattgccgcctgagcatgggcatccggcccaactctcactacatcctgagaagcggcctgctgaagtataatctgagcgacggcgagaaccctaaggtggtgtttatcgagatctccgatcagaggctgtctatcggctctcccagcaagatctacgactccctgggccagcccgtgttctaccaggcctccttttcttgggacacaatgatcaagttcggcgatgtgctgaccgtgaatccactggtggtgaactggagaaacaataccgtgatcagcaggccaggacagtcccagtgtcctcgctttaacacatgcccagagatctgttgggagggcgtgtacaatgacgccttcctgatcgatcggatcaactggatctccgccggcgtgtttctggactctaatcagaccgccgagaaccccgtgttcacagtgtttaaggataatgagatcctgtacagggcacagctggcaagcgaggacaccaacgcccagaagaccatcacaaattgcttcctgctgaagaacaagatctggtgtatctccctggtggagatctatgacaccggcgataacgtgatccggccaaagctgtttgccgtgaagatccccgagcagtgcacaggcggcctggtgcctagaggctctcaccaccaccatcaccacagcgcctggtcccacccccagttcgagaagtgataggatcc

NiVop08-Fd-G(SEQ ID NO:66，其编码SEQ ID NO:60)

tctagagccaccatgtactctatgcagctggccagctgcgtgaccctgacactggtgctgctggtgaactctcagggcatcctgcactacgagaagctgagcaagatcggcctggtgaagggcgtgaccagaaagtataagatcaagtccaacccactgacaaaggacatcgtgatcaagatgatccccaacgtgagcaatatgtctcagtgtaccggctctgtgatggagaactacaagacccgcctgaatggcatcctgacaccaatcaagggcgccctggagatctataagaacaatacacacgactgcgtgggcgatgtgcggctggcaggcgtgtgcatggcaggagtggcaatcggaatcgcaaccgcagcacagatcacagcaggagtggccctgtatgaggccatgaagaacgccgacaacatcaataagctgaagagctccatcgagagcaccaatgaggccgtggtgaagctgcaggagacagccgagaagacagtgtacgtgttcacagccctgcaggactatatcaacaccaatctggtgcccacaatcgataagatcccctgcaagcagaccgagctgtccctggacctggccctgtctaagtacctgagcgatctgctgttcgtgtttggcccaaacctgcaggaccccgtgtccaattctatgacaatccaggccatctcccaggccttcggcggcaattacgagacactgctgagaacactgggctatgccaccgaggactttgacgatctgctggagagcgattccatcacaggccagatcatctatgtggatctgtctagctactatatcatcgtgagggtgtacttccctatcctgaccgagatccagcaggcctatatccaggagctgctgccagtgagcttcaacaatgacaattccgagtggatctctatcgtgcccaactttatcctggtgcggaacaccctgatcagcaatatcgagatcggcttttgcctgatcacaaagagatccgtgatctgtaatcaggactacgccacccccatgacaaacaatatgagggagtgcctgaccggctccacagagaagtgtccccgggagctggtggtgtcctctcacgtgcctagattcgccctgtccaacggcgtgctgtttgccaattgcatctctgtgacctgccagtgtcagaccacaggaagggcaatctctcagagcggagagcagaccctgctgatgatcgataacaccacatgtcctacagccgtgctgggcaatgtgatcatcagcctgggcaagtacctgggctccgtgaactataattctgagggaatcgcaatcggaccacccgtgttcaccgacaaggtggatatcagctcccagatctctagcatgaaccagagcctgcagcagtccaaggactacatcaaggaggcccagcggctgctggataccgtgaatccttctctgggatctggttacatcccagaggctccgcgggatggacaggcctacgtgagaaaggacggcgagtgggtgctgctgagcaccttcctgggaagcggtggaggaggcggaggcgtgagcaatctggtgggcctgcccaacaatatctgtctgcagaagacctccaaccagatcctgaagcccaagctgatctcctatacactgcctgtggtgggccagtctggcacctgcatcacagaccctctgctggccatggatgagggctacttcgcctattctcacctggagaggatcggctcctgttctcgcggcgtgagcaagcagcggatcatcggagtgggagaggtgctggacaggggcgatgaggtgccttccctgttcatgaccaacgtgtggacaccacccaatccaaacaccgtgtaccactgctctgccgtgtataacaatgagttttactacgtgctgtgcgccgtgagcaccgtgggcgatcctatcctgaactccacatactggagcggctccctgatgatgaccagactggccgtgaagccaaagtccaatggcggcggctataaccagcaccagctggccctgagatctatcgagaagggcaggtacgataaagtgatgccttatggcccatctggcatcaagcagggcgacacactgtacttccccgccgtgggctttctggtgaggaccgagttcaagtacaatgactccaactgccctatcacaaagtgtcagtattctaagccagagaattgccgcctgagcatgggcatccggcccaactctcactacatcctgagaagcggcctgctgaagtataatctgagcgacggcgagaaccctaaggtggtgtttatcgagatctccgatcagaggctgtctatcggctctcccagcaagatctacgactccctgggccagcccgtgttctaccaggcctccttttcttgggacacaatgatcaagttcggcgatgtgctgaccgtgaatccactggtggtgaactggagaaacaataccgtgatcagcaggccaggacagtcccagtgtcctcgctttaacacatgcccagagatctgttgggagggcgtgtacaatgacgccttcctgatcgatcggatcaactggatctccgccggcgtgtttctggactctaatcagaccgccgagaaccccgtgttcacagtgtttaaggataatgagatcctgtacagggcacagctggcaagcgaggacaccaacgcccagaagaccatcacaaattgcttcctgctgaagaacaagatctggtgtatctccctggtggagatctatgacaccggcgataacgtgatccggccaaagctgtttgccgtgaagatccccgagcagtgcacaggcggcctggtgcctagaggctctcaccaccaccatcaccacagcgcctggtcccacccccagttcgagaagtgataggatcc

G-Fd-G(SEQ ID NO:67，其编码SEQ ID NO:37)

tctagagccaccatgtactctatgcagctggccagctgcgtgaccctgacactggtgctgctggtgaactctcaggagggcgtgagcaatctggtgggcctgcccaacaatatctgtctgcagaagacctccaaccagatcctgaagcccaagctgatctcctatacactgcctgtggtgggccagtctggcacctgcatcacagaccctctgctggccatggatgagggctacttcgcctattctcacctggagaggatcggctcctgttctcgcggcgtgagcaagcagcggatcatcggagtgggagaggtgctggacaggggcgatgaggtgccttccctgttcatgaccaacgtgtggacaccacccaatccaaacaccgtgtaccactgctctgccgtgtataacaatgagttttactacgtgctgtgcgccgtgagcaccgtgggcgatcctatcctgaactccacatactggagcggctccctgatgatgaccagactggccgtgaagccaaagtccaatggcggcggctataaccagcaccagctggccctgagatctatcgagaagggcaggtacgataaagtgatgccttatggcccatctggcatcaagcagggcgacacactgtacttccccgccgtgggctttctggtgaggaccgagttcaagtacaatgactccaactgccctatcacaaagtgtcagtattctaagccagagaattgccgcctgagcatgggcatccggcccaactctcactacatcctgagaagcggcctgctgaagtataatctgagcgacggcgagaaccctaaggtggtgtttatcgagatctccgatcagaggctgtctatcggctctcccagcaagatctacgactccctgggccagcccgtgttctaccaggcctccttttcttgggacacaatgatcaagttcggcgatgtgctgaccgtgaatccactggtggtgaactggagaaacaataccgtgatcagcaggccaggacagtcccagtgtcctcgctttaacacatgcccagagatctgttgggagggcgtgtacaatgacgccttcctgatcgatcggatcaactggatctccgccggcgtgtttctggactctaatcagaccgccgagaaccccgtgttcacagtgtttaaggataatgagatcctgtacagggcacagctggcaagcgaggacaccaacgcccagaagaccatcacaaattgcttcctgctgaagaacaagatctggtgtatctccctggtggagatctatgacaccggcgataacgtgatccggccaaagctgtttgccgtgaagatccccgagcagtgcacaggcggcggatctggttacatcccagaggctccgcgggatggacaggcctacgtgagaaaggacggcgagtgggtgctgctgagcaccttcctgggaagcggtggaggaggcggaggcgtgagcaatctggtgggcctgcccaacaatatctgtctgcagaagacctccaaccagatcctgaagcccaagctgatctcctatacactgcctgtggtgggccagtctggcacctgcatcacagaccctctgctggccatggatgagggctacttcgcctattctcacctggagaggatcggctcctgttctcgcggcgtgagcaagcagcggatcatcggagtgggagaggtgctggacaggggcgatgaggtgccttccctgttcatgaccaacgtgtggacaccacccaatccaaacaccgtgtaccactgctctgccgtgtataacaatgagttttactacgtgctgtgcgccgtgagcaccgtgggcgatcctatcctgaactccacatactggagcggctccctgatgatgaccagactggccgtgaagccaaagtccaatggcggcggctataaccagcaccagctggccctgagatctatcgagaagggcaggtacgataaagtgatgccttatggcccatctggcatcaagcagggcgacacactgtacttccccgccgtgggctttctggtgaggaccgagttcaagtacaatgactccaactgccctatcacaaagtgtcagtattctaagccagagaattgccgcctgagcatgggcatccggcccaactctcactacatcctgagaagcggcctgctgaagtataatctgagcgacggcgagaaccctaaggtggtgtttatcgagatctccgatcagaggctgtctatcggctctcccagcaagatctacgactccctgggccagcccgtgttctaccaggcctccttttcttgggacacaatgatcaagttcggcgatgtgctgaccgtgaatccactggtggtgaactggagaaacaataccgtgatcagcaggccaggacagtcccagtgtcctcgctttaacacatgcccagagatctgttgggagggcgtgtacaatgacgccttcctgatcgatcggatcaactggatctccgccggcgtgtttctggactctaatcagaccgccgagaaccccgtgttcacagtgtttaaggataatgagatcctgtacagggcacagctggcaagcgaggacaccaacgcccagaagaccatcacaaattgcttcctgctgaagaacaagatctggtgtatctccctggtggagatctatgacaccggcgataacgtgatccggccaaagctgtttgccgtgaagatccccgagcagtgcacaggcggcctggtgcctagaggctctcaccaccaccatcaccacagcgcctggtcccacccccagttcgagaagtgataggatcc

具有NiVop08取代的全长NiV F(SEQ ID NO:33)

tctagagccaccatggtggtcatcctggacaagagatgctactgtaacctgctgatcctgatcctgatgatcagcgagtgctccgtgggcatcctgcactacgagaagctgtccaagatcggcctggtgaagggcgtgaccaggaagtataagatcaagtctaatcccctgacaaaggatatcgtgatcaagatgatccctaacgtgtctaatatgagccagtgtaccggctccgtgatggagaactacaagaccagactgaatggcatcctgacacccatcaagggcgccctggagatctataagaacaatacacacgactgcgtgggcgatgtgaggctggcaggcgtgtgcatggcaggagtggcaatcggaatcgcaaccgcagcacagatcacagcaggagtggccctgtatgaggccatgaagaacgccgacaacatcaataagctgaagagctccatcgagagcaccaatgaggccgtggtgaagctgcaggagaccgccgagaagacagtgtacgtgttcacagccctgcaggactatatcaacaccaatctggtgcctacaatcgataagatcccttgcaagcagaccgagctgagcctggacctggccctgagcaagtacctgtccgatctgctgttcgtgtttggcccaaacctgcaggaccccgtgagcaattccatgacaatccaggccatctcccaggccttcggcggcaactacgagaccctgctgcgcacactgggctatgccaccgaggactttgacgatctgctggagtctgatagcatcacaggccagatcatctatgtggacctgtctagctactatatcatcgtgcgggtgtacttcccaatcctgaccgagatccagcaggcctatatccaggagctgctgcccgtgtccttcaacaatgataactctgagtggatcagcatcgtgcctaacttcatcctggtgcggaacaccctgatctctaatatcgagatcggcttttgcctgatcacaaagcgcagcgtgatctgtaatcaggactacgccacccctatgacaaacaatatgcgggagtgcctgaccggcagcacagagaagtgtcctcgggagctggtggtgtcctctcacgtgccaagattcgccctgtccaacggcgtgctgtttgccaattgcatctctgtgacctgccagtgtcagaccacaggcagggccatctcccagtctggcgagcagaccctgctgatgatcgataacaccacatgtccaacagccgtgctgggcaatgtgatcatcagcctgggcaagtacctgggcagcgtgaactataattccgagggaatcgcaatcggaccacccgtgttcaccgacaaggtggatatcagctcccagatctctagcatgaaccagtccctgcagcagtctaaggactacatcaaggaggcccagcgcctgctggataccgtgaatccatccctgatctctatgctgagcatgatcatcctgtatgtgctgtccatcgcctctctgtgcatcggcctgatcaccttcatcagctttatcatcgtggagaagaagaggaacacatactcccgcctggaggacaggagagtgcggcccacctcctctggcgatctgtactatatcggcacatgatgaggatcc

示例性核酸可以通过克隆技术制备。适当的克隆和测序技术的实例以及足以指导技术人员进行许多克隆练习的说明是已知的(参见，例如，Sambrook et al.(MolecularCloning:A Laboratory Manual,4

核酸也可以通过扩增方法制备。扩增方法包括聚合酶链反应(PCR)、连接酶链反应(LCR)、基于转录的扩增系统(TAS)、自持序列复制系统(3SR)。多种克隆方法、宿主细胞和体外扩增方法是技术人员熟知的。

编码NiV F胞外域三聚体的原聚体的多核苷酸可以包括重组DNA，该重组DNA可以掺入载体(诸如表达载体)，自动复制质粒或病毒或原核生物或真核生物的基因组DNA中，或者作为独立于其他序列的独立分子(诸如cDNA)存在。核苷酸可以是核糖核苷酸、脱氧核糖核苷酸或任一核苷酸的修饰形式。该术语包括DNA的单链形式和双链形式。

编码NiV F胞外域三聚体的原聚体的多核苷酸序列可以与表达控制序列可操作地连接。连接与编码序列可操作连接的表达控制序列，使得在与表达控制序列相容的条件下实现编码序列的表达。表达控制序列包括但不限于适当的启动子、增强子、转录终止子、蛋白编码基因前面的起始密码子(即ATG)、内含子的剪接信号，维持该基因的正确阅读框以实现mRNA正确翻译，并终止密码子。

可以通过将DNA转移到合适的宿主细胞中在体外表达编码NiV F胞外域三聚体的原聚体的DNA序列。该细胞可以是原核的或真核的。该术语还包括受试者宿主细胞的任何后代。应当理解，所有后代可能与亲代细胞并不相同，因为在复制过程中可能发生突变。稳定转移的方法是指外源DNA在宿主中连续保持，这是本领域已知的。

宿主可以包括微生物、酵母、昆虫和哺乳动物生物。在原核生物中表达具有真核或病毒序列的DNA序列的方法是本领域熟知的。合适的宿主细胞的非限制性实例包括细菌、古细菌、昆虫、真菌(例如酵母)、植物和动物细胞(例如哺乳动物细胞，诸如人)。使用的示例性细胞包括大肠杆菌、枯草芽孢杆菌、酿酒酵母、鼠伤寒沙门氏菌、SF9细胞、C129细胞、293细胞、链孢霉和永生化的哺乳动物骨髓和淋巴样细胞系。用于在培养物中繁殖哺乳动物细胞的技术是公知的(参见，例如，Helgason and Miller(Eds.),2012,Basic Cell CultureProtocols(Methods in Molecular Biology),4

用重组DNA转化宿主细胞可以通过常规技术进行。在宿主是原核生物(例如但不限于大肠杆菌)的一些实施方式中，能够从指数生长期之后收获的细胞中制备能够吸收DNA的感受态细胞，然后通过CaCl

当宿主是真核生物时，可以使用诸如磷酸钙共沉淀之类的DNA转染方法，常规的机械方法，诸如显微注射、电穿孔、装入脂质体中的质粒插入或病毒载体。真核细胞还可以与编码已公开抗原的多核苷酸序列和编码可选择表型的第二外源DNA分子，诸如单纯疱疹胸苷激酶基因一起共转化。另一种方法是使用真核病毒载体，诸如猿猴病毒40(SV40)或牛乳头瘤病毒，以瞬时感染或转化真核细胞并表达该蛋白(参见，例如，Viral ExpressionVectors,Springer press,Muzyczka ed.,2011)。适当的表达系统诸如质粒和载体，用于在包括高等真核细胞(诸如COS、CHO、HeLa和骨髓瘤细胞系)的细胞中产生蛋白。

在一个非限制性实例中，使用pVRC8400载体表达公开的免疫原(描述于Barouchet al.,J.Virol.,79,8828-8834,2005，其通过引用并入本文)。

可以对编码公开的免疫原的核酸进行修饰而不降低其生物学活性。可以进行一些修饰以促进靶向分子的克隆、表达或掺入融合蛋白。示例性修饰包括终止密码子、在氨基末端添加以提供起始位点的甲硫氨酸、置于任一末端以产生方便定位的限制性位点的其他氨基酸、或有助于纯化步骤的其他氨基酸(诸如poly His)。

在一些实施方式中，编码公开的重组NiV F胞外域原聚体的原聚体的核酸可以在以下条件下在细胞中表达，在该条件下，原聚体自组装成三聚体，其从细胞分泌到细胞培养基中，例如对于RSV F蛋白的描述(参见，例如，PCT Pub.WO2014160463,McLellan et al.,Science,340:1113-1117,2013；McLellan et al.,Science,342:592-598,2013，其各自通过引用以其全文并入本文)。在这样的实施方式中，原聚体包含导致蛋白进入分泌系统的前导序列(信号肽)，并且信号肽在被分泌到细胞培养基中之前被切割，并且原聚体形成三聚体。可以离心培养基，并从上清液中纯化重组NiV F胞外域三聚体。

III.病毒载体

编码公开的免疫原的核酸分子可以包含在病毒载体中，例如，用于在宿主细胞中表达免疫原，或用于免疫本文所公开的受试者。在一些实施方式中，将病毒载体作为初免-加强疫苗接种的一部分施用于受试者。通常，此类病毒载体包括编码包含跨膜结构域的免疫原的核酸分子。在一些实施方式中，病毒载体包括在疫苗中，例如用于初免-加强型疫苗接种的初免疫苗或加强疫苗。

在一些实例中，病毒载体可以是具有复制能力的。例如，病毒载体可以在病毒基因组中具有突变(例如，插入编码原聚体的核酸)，其减弱但不完全阻断宿主细胞中的病毒复制。

在一些实施方式中，病毒载体可以通过呼吸道递送。例如，hPIV载体，诸如牛副流感病毒(BPIV)载体(例如，BPIV1、BPIV2或BPIV3载体)或人hPIV载体(例如，hPIV3载体)、间质肺病毒(MPV)载体、仙台病毒载体或麻疹病毒载体，用于表达公开的抗原。

另外的病毒载体也可用于表达所公开的抗原，包括多瘤病毒，即SV40(Madzak etal.,1992,J.Gen.Virol.,73:15331536)，腺病毒(Berkner,1992,Cur.Top.Microbiol.Immunol.,158:39-6；Berliner et al.,1988,Bio Techniques,6:616-629；Gorziglia et al.,1992,J.Virol.,66:4407-4412；Quantin et al.,1992,Proc.Natl.Acad.Sci.USA,89:2581-2584；Rosenfeld et al.,1992,Cell,68:143-155；Wilkinson et al.,1992,Nucl.Acids Res.,20:2233-2239；Stratford-Perricaudet etal.,1990,Hum.Gene Ther.,1:241-256)，牛痘病毒(Mackett et al.,1992,Biotechnology,24:495-499)，腺相关病毒(Muzyczka,1992,Curr.Top.Microbiol.Immunol.,158:91-123；On et al.,1990,Gene,89:279-282)，疱疹病毒，包括HSV、EBV和CMV(Margolskee,1992,Curr.Top.Microbiol.Immunol.,158:67-90；Johnson et al.,1992,J.Virol.,66:29522965；Fink et al.,1992,Hum.Gene Ther.3:11-19；Breakfield et al.,1987,Mol.Neurobiol.,1:337-371；Fresse et al.,1990,Biochem.Pharmacol.,40:2189-2199)，Sindbis病毒(H.Herweijer et al.,1995,HumanGene Therapy 6:1161-1167；美国专利号5,091,309和5,2217,879)，甲病毒(S.Schlesinger,1993,Trends Biotechnol.11:18-22；I.Frolov et al.,1996,Proc.Natl.Acad.Sci.USA 93:11371-11377)以及禽源逆转录病毒(Brandyopadhyay etal.,1984,Mol.Cell Biol.,4:749-754；Petropouplos et al.,1992,J.Virol.,66:3391-3397)，鼠源逆转录病毒(Miller,1992,Curr.Top.Microbiol.Immunol.,158:1-24；Milleret al.,1985,Mol.Cell Biol.,5:431-437；Sorge et al.,1984,Mol.Cell Biol.,4:1730-1737；Mann et al.,1985,J.Virol.,54:401-407)和人源逆转录病毒(Page et al.,1990,J.Virol.,64:5370-5276；Buchschalcher et al.,1992,J.Virol.,66:2731-2739)。杆状病毒(Autographa californica multinuclear polyhedrosis virus；AcMNPV)载体也是本领域已知的，可以从商业来源获得(诸如PharMingen,San Diego,Calif.；Protein SciencesCorp.,Meriden,Conn.；Stratagene,La Jolla,Calif.)。

IV.病毒样颗粒

在一些实施方式中，提供了包括公开的免疫原的病毒样颗粒(VLP)。通常，这样的VLP包括含有跨膜结构域的免疫原，例如具有含有NiV F跨膜结构域和胞质尾的原聚体的重组NiV F胞外域三聚体。VLP缺乏病毒复制所需的病毒成分，因此代表高度减毒、无复制能力的病毒。然而，VLP可以展示类似于在感染性病毒颗粒上表达的多肽(例如，重组NiV F胞外域三聚体)，并且当施用于受试者时可以引发针对NiV的免疫应答。示例性的病毒样颗粒及其产生方法，以及来自几种已知可形成VLP的病毒的病毒蛋白，包括人乳头瘤病毒、HIV(Kang et al.,Biol.Chem.380:353-64(1999))、Semliki-Forest病毒(Notka et al.,Biol.Chem.380:341-52(1999))、人多瘤病毒(Goldmann et al.,J.Virol.73:4465-9(1999)),rotavirus(Jiang et al.,Vaccine 17:1005-13(1999))、轮状病毒(Jiang etal.,Vaccine 17:1005-13(1999))、细小病毒(Casal，Biotechnology and AppliedBiochemistry，Vol 29，Part 2，pp 141-150(1999))、犬细小病毒(Hurtado et al.,J.Virol.70:5422-9(1996))、戊型肝炎病毒(Li et al.,J.Virol.71:7207-13(1997))和新城疫病毒(Newcastle disease virus)。可以通过任何合适的技术来检测这种VLP的形成。用于检测介质中VLP的合适技术的示例包括，例如电子显微镜技术、动态光散射(DLS)、选择性色谱分离(例如，VLP的离子交换、疏水相互作用和/或尺寸排阻色谱分离)和密度梯度离心。

V.免疫原性组合物

还提供了免疫原性组合物，其包括公开的免疫原(例如，重组NiV F胞外域三聚体、编码重组NiV F胞外域三聚体的原聚体的核酸分子或载体、或包括公开的重组NiV F胞外域三聚体的蛋白纳米颗粒或病毒样颗粒)以及药学上可接受的载体。这样的组合物可以通过多种施用方式施用，例如肌内、皮下、静脉内、动脉内、关节内、腹腔或肠胃外途径。在几个实施方式中，包括一种或更多种公开的免疫原的药物组合物是免疫原性组合物。制备可施用的组合物的实际方法在如Remingtons Pharmaceutical Sciences,19

因此，本文描述的免疫原可以与药学上可接受的载体一起配制，以帮助保留生物学活性，同时还促进在可接受温度范围内的储存过程中增加的稳定性。潜在的载体包括但不限于生理平衡的培养基、磷酸盐缓冲溶液、水、乳剂(例如油/水或水/油乳剂)、各种类型的润湿剂、防冻添加剂或稳定剂(诸如蛋白)、肽或水解产物(例如白蛋白、明胶)、糖(例如蔗糖、乳糖、山梨糖醇)、氨基酸(例如谷氨酸钠)或其他保护剂。可以将所得的水溶液包装成原样使用或冻干。冻干的制剂在施用前与无菌溶液合并以进行单次或多次给药。

配制的组合物，尤其是液体制剂，可以包含抑菌剂以防止或最小化在储存过程中的降解，包括但不限于有效浓度(通常≤1％w/v)的苯甲醇、苯酚、间甲酚、氯丁醇、对羟基苯甲酸甲酯和/或对羟基苯甲酸丙酯。某些患者可能禁忌使用抑菌剂。因此，冻干制剂可以在含有或不含这种组分的溶液中复溶。

本公开的免疫原性组合物可以包含近似生理条件所需的药学上可接受的溶媒物质，例如pH调节剂和缓冲剂、张力调节剂、润湿剂等，例如乙酸钠、乳酸钠、氯化钠、氯化钾、氯化钙、脱水山梨糖醇单月桂酸酯和三乙醇胺油酸酯。

免疫原性组合物可任选地包含佐剂以增强宿主的免疫应答。佐剂，诸如氢氧化铝(

在一些情况下，佐剂制剂是无机盐，诸如钙或铝(alum)盐，例如磷酸钙、磷酸铝或氢氧化铝。在一些实施方式中，佐剂包括油和水乳剂，例如水包油乳剂(诸如MF59(Novartis)或AS03(GlaxoSmithKline)。水包油乳液的一个实例包括水性载体中的可代谢的油，诸如角鲨烯；母育酚，诸如生育酚，例如α-生育酚；和表面活性剂，诸如脱水山梨醇三油酸酯(Span 85)或聚氧乙烯脱水山梨醇单油酸酯(Tween 80)。

在某些情况下，可能希望将公开的免疫原与诱导对其他试剂的保护性反应的其他药物产品(例如疫苗)组合。例如，可以将本文所述的包含重组NiV F胞外域三聚体的组合物与免疫实践咨询委员会(ACIP；cdc.gov/vaccines/acip/index.html)推荐的其他疫苗同时(通常单独)或序贯施用用于目标年龄段(例如，约一到六个月龄的婴儿)。如此，本文所述的公开的免疫原可以与针对例如乙型肝炎(HepB)、白喉、破伤风和百日咳(DTaP)、肺炎球菌(PCV)、b型乙型流感嗜血杆菌(Hib)、脊髓灰质炎、流感和轮状病毒的疫苗同时或序贯施用。

在一些实施方式中，组合物可以无菌组合物的形式提供。免疫原性组合物通常包含有效量的公开的免疫原，并且可以通过常规技术制备。通常，选择每剂免疫原性组合物中的免疫原的量作为诱导免疫应答而没有明显不利副作用的量。在一些实施方式中，可以以单位剂型提供组合物，以用于诱导受试者产生免疫应答，例如，抑制受试者的NiV感染。单位剂型包含用于施用于受试者的合适的单一预选剂量，或两个或更多个预选单位剂量的合适的标记或测量倍数，和/或用于施用单位剂量或其倍数的计量机制。

VI.诱导免疫应答的方法

可以将公开的免疫原(例如，重组的融合前稳定的NiV F胞外域三聚体，编码融合前稳定的NiV F胞外域三聚体的原聚体的核酸分子(诸如RNA分子)或载体，或包含融合前稳定的NiV F胞外域三聚体的蛋白纳米颗粒或病毒样颗粒)施用于受试者以诱导受试者产生针对NiV的免疫应答。在特定的实例中，受试者是人。免疫应答可以是保护性免疫应答，例如抑制随后的NiV感染的应答。免疫应答的引发也可用于治疗或抑制NiV感染及其相关疾病。

可以选择例如由于暴露或可能暴露于NiV而患有NiV感染或具有发展NiV感染风险的受试者。在施用公开的免疫原之后，可以监测受试者的NiV感染或与其相关的症状，或两者。

计划接受本公开的疗法和方法进行治疗的典型受试者包括人和家畜，诸如猪。在几个实施方式中，受试者是对NiV特异性抗体呈血清反应阴性的人类受试者。为了根据本公开的方法鉴定用于预防或治疗的受试者，采用公认的筛选方法来确定与目标或可疑疾病或病症相关的风险因素，或确定受试者中现有疾病或病症的状态。这些筛选方法包括，例如常规检查以确定可能与目标或可疑疾病或病症相关的环境、家族、职业和其他此类风险因素，以及诊断方法，诸如各种ELISA和其他用于检测和/或表征NiV感染的免疫测定方法。这些和其他常规方法允许临床医生使用本公开的方法和免疫原性组合物选择需要治疗的患者。根据这些方法和原理，可以根据本文的教导或其他常规方法，以独立的预防或治疗程序，或作为其他治疗的后续，辅助或协调治疗方案来施用组合物。

所公开的免疫原的施用可以用于预防或治疗目的。当进行预防性提供时，可以在任何症状之前，例如在感染之前提供免疫原。预防性施用用于预防或减轻任何随后的感染。在一些实施方式中，该方法可以包括选择具有感染NiV感染风险中的受试者，以及向该受试者施用治疗有效量的所公开的免疫原。可以在预期的NiV暴露之前提供免疫原，以在暴露于或疑似暴露于病毒后或实际感染之后减弱预期的感染的严重程度、持续时间或程度和/或相关的疾病症状。当提供治疗时，所公开的免疫原在NiV感染症状发作时或之后，或在诊断NiV感染后提供。通过抑制NiV复制或感染来治疗NiV可包括延迟和/或减轻受试者的NiV感染的体征或症状。在一些实例中，使用本文公开的方法进行的治疗延长受试者的存活时间。

在一些实施方式中，当受试者随后感染或再感染野生型NiV时，向受试者施用公开的免疫原可以引发产生针对严重下呼吸道疾病，诸如肺炎和细支气管炎或哮吼的免疫应答。尽管自然循环的病毒仍可能能够引起感染，特别是在上呼吸道，但是由于接种疫苗导致鼻炎的可能性降低，并且由于野生型病毒的后续感染而可能增强耐药性。疫苗接种后，存在可检测水平的宿主产生的血清和分泌抗体，它们能够在体内和体外中和(同一亚组的)野生型病毒。在许多情况下，宿主抗体还将中和不同的非疫苗亚型的野生型病毒。

本文所述的免疫原及其免疫原性组合物以有效诱导或增强受试者(优选人)中针对NiV的免疫应答的量提供给受试者。公开的免疫原的实际剂量将根据以下因素变化，诸如疾病的适应症和受试者的特殊状况(例如，受试者的年龄、身高、健康状况、症状程度、易感性因素等)、施用的时间和途径、待同时施用的其他药物或治疗，以及引起受试者产生预期活性或生物学应答的组合物的特定药理作用。可以调整剂量方案以提供最佳的预防或疗效。

包括一种或更多种公开的免疫原的免疫原性组合物可以用在协同(或初免-加强)疫苗接种方案或组合制剂中。在某些实施方式中，新型组合免疫原性组合物和协同免疫方案采用单独的免疫原或制剂，其各自针对引发抗病毒免疫应答，例如对NiV F蛋白的免疫应答。可以将引发抗病毒免疫应答的单独的免疫原性组合物与在单一免疫步骤中施用于受试者的多价免疫原性组合物中联合使用，也可以在协同(或初免-加强)免疫方案中分别单独施用(在单价免疫原性组合物中)。

可以进行数次加强免疫，每次加强免疫可以是公开的不同免疫原。在一些实例中，加强可以与另一加强或初免相同。初免和加强可以以单次给药或多次给药施用，例如可以在几天、几周或几个月内向受试者施用两次给药、三次给药、四次给药、五次给药、六次给药或更多次给药。也可以提供多次加强，例如一到五次(例如1、2、3、4或5次增强)或更多。可以在一系列连续免疫中使用不同的剂量。例如，在初免中使用相对较大的剂量，然后以相对较小的剂量进行加强免疫。

在一些实施方式中，可以在初免后约两周、约三至八周或约四周或初次免疫后约几个月施用加强。在一些实施方式中，可以在初免后约5个月、约6个月、约7个月、约8个月、约10个月、约12个月、约18个月、约24个月，或初免后或多或少的时间施用加强免疫。还可以在适当的时间使用定期的其他增强措施来增强受试者的“免疫记忆”。所选择的疫苗接种参数的充分性，例如制剂、剂量、方案等，可以通过从受试者中取血清的等分试样并在免疫程序的过程中测定抗体滴度来确定。另外，可以监测受试者的临床状况的期望效果，例如抑制NiV感染或改善疾病状态(例如减少病毒载量)。如果这样的监测表明疫苗接种不是最理想的，则可以用额外剂量的免疫原性组合物加强对受试者的免疫，并且可以以预期增强免疫应答的方式来修改疫苗接种参数。

在一些实施方式中，初免-加强方法可以包括针对受试者的DNA-初免和蛋白-加强疫苗接种方案。该方法可以包括两次或更多次施用核酸分子或蛋白。

对于蛋白治疗剂，通常，每个人剂量将包含1-1000μg蛋白，诸如约1μg至约100μg，例如，约1μg至约50μg，诸如约1μg、约2μg、约5μg、约10μg、约15μg、约20μg、约25μg、约30μg、约40μg或约50μg。免疫原性组合物中使用的量根据受试者群体(例如婴儿或老年人)选择。可以通过标准研究确定特定组合物的最佳量，这些标准研究包括观察受试者的抗体效价和其他应答。应当理解的是，治疗有效量的所公开的免疫原，诸如重组NiV F胞外域或其免疫原性片段、病毒载体、或免疫原性组合物中的核酸分子，可以包括通过单次给药施用在引起免疫应答方面无效的量，但是在例如以初免-加强施用方案施用时，在多次给药后有效。

在施用公开的免疫原后，受试者的免疫系统通常通过产生对病毒蛋白具有特异性的抗体产生对免疫原性组合物的应答。这种应答表明已向受试者递送了免疫学有效剂量。

对于每个特定受试者，可以根据个体需要和对免疫原性组合物的施用或监督的人的专业判断来评估和调整特定的剂量方案。剂量和给药次数将取决于具体情况，例如，在成年人或既往NiV感染或免疫引发的任何人中，单次给药可能是足够的加强剂量。在一些实例中，在未接受治疗的受试者中，将给予至少两次给药，例如，至少三次给药。在一些实施方式中，例如与年度流感疫苗一起给予年度加强。

在一些实施方式中，将在评估有效剂量/免疫方案的情况下确定受试者的抗体应答。在大多数情况下，评估从受试者获得的血清或血浆中的抗体效价足够。是否施用加强接种和/或改变施用于个体的治疗剂的量的决定可以至少部分地基于抗体效价水平。抗体效价水平可以基于例如免疫结合测定法，其测量血清中与包括例如NiV F蛋白的抗原结合的抗体的浓度。

有效剂量的确定通常基于动物模型研究，随后进行人体临床试验，并以可显著减少受试者体内目标疾病症状或病状的发生或严重程度或在受试者中诱发预期应答的给药方案为指导(诸如中和性免疫应答)。在这方面，合适的模型包括例如鼠、大鼠、猪、猫、雪貂、非人灵长类动物和本领域已知的其他可接受的动物模型受试者。可选地，可以使用体外模型(例如，免疫学和组织病理学测定)确定有效剂量。使用此类模型，仅需常规计算和调整即可确定合适的浓度和剂量，以施用治疗有效量的组合物(例如，有效引发预期免疫应答或缓解目标疾病的一种或更多种症状的量)。在可选的实施方式中，出于治疗或诊断目的，组合物的有效量或有效剂量可以简单地抑制或增强与疾病或病症相关的一种或更多种选择的生物学活性，如本文所述。

施用引发免疫应答以减少或预防感染的免疫原性组合物就可以但不必要完全消除这种感染，只要可测量地减少感染即可。例如，施用有效量的试剂可以减少NiV感染(例如，通过细胞感染或被NiV感染的受试者的数量或百分比来测量)，例如与合适的对照相比，消除或预防可检测的NiV感染至少10％、至少20％、至少50％、至少60％、至少70％、至少80％、至少90％、至少95％、至少98％或甚至至少100％。

在一些实施方式中，向受试者施用治疗有效量的一种或更多种所公开的免疫原可以诱导受试者产生中和性免疫应答。为了评估中和活性，在对受试者进行免疫之后，可以在适当的时间点从受试者收集血清，将其冷冻并储存用于中和检测。用于测定中和活性的方法包括但不限于噬斑减少中和(PRNT)测定、微中和测定、基于流式细胞仪的测定、单周期感染测定。在一些实施方式中，可以使用一组NiV假病毒来测定血清中和活性。

施用核酸的一种方法是用质粒DNA，诸如用哺乳动物表达质粒直接免疫。通过核酸构建体的免疫是本领域熟知的，并且例如在美国专利号5,643,578(其描述了通过引入编码预期抗原的DNA引发细胞介导或体液反应来免疫脊椎动物的方法)，以及美国专利号5,593,972和美国专利号5,817,637(其描述了将编码抗原的核酸序列可操作地连接至能够表达的调节序列)中有教导。美国专利号5,880,103描述了几种将编码免疫原性肽或其他抗原的核酸递送至生物体的方法。这些方法包括脂质体递送核酸(或合成肽本身)，免疫刺激的构建体或ISCOMS

在一些实施方式中，质粒DNA疫苗用于在受试者中表达公开的免疫原。例如，可以将编码公开的免疫原的核酸分子施用于受试者以引发针对NiV的F蛋白的免疫应答。在一些实施方式中，核酸分子可以包含在用于DNA免疫的质粒载体上，例如pVRC8400载体(描述于Barouch et al.,J.Virol,79,8828-8834,2005，其通过引用并入本文)。

在使用核酸进行免疫的另一种方法中，公开的免疫原可以通过减毒的病毒宿主(诸如减毒的NiV载体)或载体或细菌载体表达。重组牛痘病毒、腺相关病毒(AAV)、疱疹病毒、逆转录病毒、巨细胞病毒(cytogmeglovirus)或其他病毒载体可用于表达肽或蛋白，从而引发CTL应答。例如，在免疫方案中有用的痘苗载体和方法在美国专利号4,722,848中描述。BCG(卡介苗芽孢杆菌(Bacillus Calmette Guerin))提供了另一种用于表达肽的载体(参见Stover,Nature 351:456-460,1991)。

在另一实例中，可以使用RNA免疫，诸如用脂质包裹的mRNA免疫平台，将公开的免疫原施用于受试者(参见，例如，Roth et al.,“A Modified mRNA Vaccine TargetingImmunodominant NS Epitopes Protects Against Dengue Virus Infection in HLAClass I Transgenic Mice,”Frot Immunol.,June 21,2019,Vol.10,Article 1424；Jagger et al.,J Infect Dis,“Protective Efficacy of Nucleic Acid VaccinesAgainst Transmission of Zika Virus During Pregnancy in Mice,”jiz338,Jul 1,2019；Feldman et al.,“mRNA vaccines against H10N8 and H7N9 influenza virusesof pandemic potential are immunogenic and well tolerated in healthy adults inphase 1randomized clinical trials,”Vaccine,37(25),3326-3334,2019；和Hasset etal.,“Optimization of Lipid Nanoparticles for Intramuscular Administration ofmRNA Vaccines,”Mol Ther Nucleic Acids,15:1-11,2019)。

在一个实施方式中，将编码公开的NiV F胞外域三聚体的原聚体的核酸直接引入细胞中。例如，可以通过标准方法将核酸负载到金微球上，然后通过诸如Bio-Rad’sHELIOS

实施例

提供以下实施例以举例说明某些实施方式的特定特征，但是权利要求的范围不应限于所举例说明的那些特征。

实施例1

以融合前构象稳定的NiV F蛋白

本实施例说明了通过一个或更多个氨基酸取代以融合前构象稳定的NiV F胞外域三聚体的实施方式。融合前稳定的NiV F胞外域三聚体可用于例如诱导受试者产生对NiV的中和免疫应答。

当最初在细胞中产生时，连接至C端GCN4三聚结构域的NiV F胞外域形成三聚体，这些三聚体大多数为融合前构象。但是，当储存在4℃下时，亚稳态三聚体经历逐渐结构转变以形成NiV F融合后构象。

因此，基于结构的疫苗设计用于鉴定将NiV F胞外域稳定为融合前构象(基于融合前NiV F结构PDB ID 2B9B)的突变，也用于消除F1/F2切割位点以产生“增强表达的单链NiVF蛋白。几种不同的稳定化策略被用来将NiV F胞外域“锁定”在融合前构象，包括引入二硫键、填充空腔的氨基酸取代和脯氨酸取代。总共设计、表达、纯化和评估了约150种不同的突变体，以评估其表达水平以及与对NiV F的融合前构象具有特异性的抗体5B3的结合。在检测的150多个构建体中，以下显示了融合前稳定和蛋白表达的最佳组合：NiV05、NiV07、NiV08、NiV09、NiV11、NiV12、NiV13、NiV14、NiV15和NiV16。

将突变引入连接至C端GCN4三聚结构域的NiV F胞外域，并使用融合前的NiV F抗体5B3在96孔微培养高通量微表达和ELISA分析中筛选所得突变体。产生并表达约150种构建体，包括：

连接至GCN4三聚结构域的野生型胞外域

NiV01:NiV F(22-497)GCN4

具有F2/F1融合并连接至GCN4三聚结构域的单链胞外域

NiV02:NiV F(22-497)GCN4,Δ101-116，残基N100-G117通过丝氨酸连接

NiV03:NiV F(22-497)GCN4,Δ100-115，残基N99-A116通过GSG接头连接

NiV04:NiV F(22-497)GCN4,Δ102-113，残基T101-I114通过GSG接头连接

NiV06:NiV F(22-497)GCN4,Δ100-116，残基N99-G117通过GGS接头连接

NiV10:NiV F(22-497)GCN4,Δ100-116，残基N99-G117直接连接

连接至GCN4三聚结构域的融合前稳定的胞外域

NiV05:NiV F(22-497)GCN4，原聚体内L104C-I114C二硫键

NiV07:NiV F(22-497)GCN4，原聚体内I114C-I426C二硫键

NiV08:NiV F(22-497)GCN4，L172F空腔填充取代

NiV09:NiV F(22-497)GCN4，S191P

NiV11:NiV F(22-497)GCN4，Y178W空腔填充取代

NiV12:NiV F(22-497)GCN4，原聚体内A130C-V222C二硫键

NiV13:NiV F(22-497)GCN4，Q70G

NiV14:NiV F(22-497)GCN4，D188G,S191G

NiV15:NiV F(22-497)GCN4，原聚体内Q162C-T168C二硫键

NiV16:NiV F(22-497)GCN4，I228F

与相应的未修饰NiV F(NiV01)相比，单链和融合前稳定的NiV F蛋白的表达和纯化显示出表达水平的大幅提高：

负染EM用于确认NiV05、NiV07、NiV08、NiV09、NiV11、NiV12、NiV13、NiV14、NiV15和NiV16 F变体的构象。在图1A-1F中提供了示例性图像。图1F显示NiV06构建体，其具有单链突变，但是在融合后构象中没有融合前稳定突变。

接下来，还评估了融合前稳定化和蛋白生产突变的组合。在检测的许多组合中，以下显示融合前稳定和蛋白表达的最佳组合：

NiVop01:NiV F(22-497)GCN4,I114C-I426C,L172F

NiVop02:NiV F(22-497)GCN4,L104C-I114C,L172F

NiVop03:NiV F(22-497)GCN4,Δ102-113,T101-I114通过GSG连接,L172F

NiVop04:NiV F(22-497)GCN4,I114C-I426C,S191P

NiVop05:NiV F(22-497)GCN4,L104C-I114C,S191P

NiVop06:NiV F(22-497)GCN4,Δ102-113,T101-I114通过GSG连接,S191P

NiVop07:NiV F(22-497)GCN4,I114C-I426C,L172F,S191P

NiVop08:NiV F(22-497)GCN4,L104C-I114C,L172F,S191P

NiVop09:NiV F(22-497)GCN4,Δ102-113,T101-I114通过GSG连接,L172P,S191P

NiVop12:NiV F(22-497)GCN4,L172P,S191P

NiVop13:NiV F(22-497)GCN4,L172P,S191P,Q70G

NiVop14:NiV F(22-497)GCN4,L104C-I114C,L172F,S191P,Q70G

NiVop15:NiV F(22-497)GCN4,L104C-I114C,L172F,Q70G

NiVop16:NiV F(22-497)GCN4,L104C-I114C,Q70G

NiVop17:NiV F(22-497)GCN4,L104C-I114C,Q162C-T168C,L172F,S191P

NiVop18:NiV F(22-497)GCN4,L104C-I114C,A130C-V222C,L172F,S191P

这些构建体在细胞中表达，纯化并评估5B3结合。所有纯化的蛋白都与5B3结合，表明它们处于融合前构象。此外，与相应的未修饰NiV F相比，所有这些构建物均显示出表达水平的大幅提高：

负染EM显示所有这些构建体均为融合前特异性构象。单独的NiVop08和被5B3Fab结合的NiVop08的示例性负染EM图像如图2所示。

如图1-2所示，负EM可以用于区分处于融合前构象的NiV F胞外域三聚体和处于融合后构象的NiV F胞外域三聚体。

对几种修饰的NiV F胞外域三聚体进行免疫测定，以确定这些三聚体是否可以在动物模型中产生中和的免疫应答。在第0、3和10周用Alum中的10μg NiV F免疫CB6F1/J小鼠，并在第5和12周测定免疫小鼠的血清的中和效价(见图3A)。使用Octet结合测定检测免疫小鼠的血清与融合前稳定的NiV F胞外域三聚体(NiVop08)和融合后NiV F胞外域三聚体(NiV06)的结合(图3B)。将NiVop08或NiV06三聚体连接到传感器，检测指定免疫的血清的结合。获自NiVop02、NiVop05、NiVop08和NiVop12免疫动物的血清相对于融合后F(NiV06)优先结合融合前F(NiVop08)。相反，相对于融合前F(NiVop08)，获自NiV06免疫动物的血清优先结合融合后F(NiV06)。

在NiV中和测定中评估免疫血清(图3C)，其显示了获自用融合前NiV F三聚体处理的动物的免疫血清中和NiV。因此，在动物模型中，用可溶性的融合前稳定的NiV F胞外域三聚体免疫引发中和免疫应答。

方法概要

蛋白表达和纯化。使用Stratagene Quik-change程序通过定点诱变产生NiV F突变。通过用编码变体NiV F三聚体的原聚体的前体的质粒DNA瞬时转染Expi293F细胞以表达NiV F变体。转染5天后收集细胞培养上清液，并以10,000g离心以除去细胞碎片。将上清液无菌过滤，并通过镍和streptactin亲和层析，然后通过尺寸排阻层析纯化NiV F蛋白。去除镍和streptactin纯化标签以进行动物免疫。

融合前稳定的NiV F构建体的筛选。融合前NiV F变体源自天然NiV F序列。使用先前描述的针对HIV开发的高通量测定方法，使用96孔微孔板格式的瞬时基因表达方法实现各种NiV F蛋白的高通量表达((Pancera et al.,PloS one,8,e55701,2013)。简言之，转染前24小时，将HEK 293T细胞以2.5×10

负染电子显微镜观察。将样品吸附到新辉光放电碳膜栅上，用缓冲液冲洗两次，然后用新鲜制备的0.75％甲酸双氧铀染色。在配备2k x 2k Eagle CCD相机的FEI T20显微镜上以

小鼠免疫。所有动物实验均由NIAID，NIH疫苗研究中心的动物护理和使用委员会审查并批准，并且在美国国立卫生研究院(NIH)的美国实验室动物护理认可协会(AAALAC)认可的机构中，所有动物均按照当地、州、联邦和研究所的政策进行饲养和护理。在6周至12周龄时，在第0周、第3周和第10周对称为CB6F1/J的BALB/c雌性(C)和C57BL/6J雄性(B6)(Jackson Laboratory)杂交的第一子后代的杂交小鼠肌肉注射胞外域三聚体免疫原。将冷冻的NiV F胞外域三聚体变体免疫原蛋白在冰上解冻，并与Alum佐剂混合，每次免疫每只动物10μg NiV F，并在免疫原：佐剂制备后1小时内注射。未观察到免疫不良反应。至少在免疫前三天以及初次免疫后第二周、第五周和第十二周采集血液。

NiV假型的产生。为了获得用NiVF和G蛋白假型化的VSV△G-荧光素酶，首先用VRC8400 NiVF

NiV中和测定。为了测量血清中的NiV中和抗体，首先将VSV△G-荧光素酶/NiVF-G假型与抗VSV G 8G5抗体(5μg/mL)在室温下孵育30分钟，以中和由于残留的VSV G导致的任何痕量感染，这些残留的VSV G可能已掺入用NiVF

血清抗原分析。使用ForteBio Octet HTX仪器评估免疫组的小鼠血清与融合前和融合后NiV F胞外域三聚体的结合。将第5周血清在1％BSA/PBS中以1:400稀释。在进行测定之前，将从FortéBio获得的Anti penta His(HIS1K)传感器头在PBS中平衡。使用C端His标签将将NiV F三聚体蛋白(在1％BSA/PBS中)以20μg/ml负载到HIS1K生物传感器上300s。负载融合前或融合后NiV F三聚体的HIS1K头在1％BSA/PBS中平衡60s，然后进行血清缔合步骤300s，随后进行解离步骤300s。使用Octet和GraphPad Prism 6软件进行数据分析。

序列：

NiV01(SEQ ID NO:1)

mysmqlascvtltlvllvnsQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSDMSQCTGSVMENYKTRLNGILTPIKGALEIYKNNTHDLVGDVRLAGVIMAGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVLTALQDYINTNLVPTIDKISCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDDSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLklmkqiedkieeilskiyhieneiarikkligeapgglvprgshhhhhhsawshpqfek

NiV02(SEQ ID NO:2)

mysmqlascvtltlvllvnsQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSQCTGSVMENYKTRLNGILTPIKGALEIYKNNSGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVLTALQDYINTNLVPTIDKISCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLklmkqiedkieeilskiyhieneiarikkligeapgglvprgshhhhhhsawshpqfek

NiV03(SEQ ID NO:3)

mysmqlascvtltlvllvnsQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSQCTGSVMENYKTRLNGILTPIKGALEIYKNGSGAGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVLTALQDYINTNLVPTIDKISCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLklmkqiedkieeilskiyhieneiarikkligeapgglvprgshhhhhhsawshpqfek

NiV04(SEQ ID NO:4)

mysmqlascvtltlvllvnsQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSQCTGSVMENYKTRLNGILTPIKGALEIYKNNTGSGIMAGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVLTALQDYINTNLVPTIDKISCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLklmkqiedkieeilskiyhieneiarikkligeapgglvprgshhhhhhsawshpqfek

NiV05(SEQ ID NO:5)

mysmqlascvtltlvllvnsQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSQCTGSVMENYKTRLNGILTPIKGALEIYKNNTHDCVGDVRLAGVCMAGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVLTALQDYINTNLVPTIDKISCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLklmkqiedkieeilskiyhieneiarikkligeapgglvprgshhhhhhsawshpqfek

NiV06(SEQ ID NO:6)

mysmqlascvtltlvllvnsQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSQCTGSVMENYKTRLNGILTPIKGALEIYKNGGSGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVLTALQDYINTNLVPTIDKISCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLklmkqiedkieeilskiyhieneiarikkligeapgglvprgshhhhhhsawshpqfek

NiV07(SEQ ID NO:7)

mysmqlascvtltlvllvnsQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSQCTGSVMENYKTRLNGILTPIKGALEIYKNNTHDLVGDVRLAGVCMAGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVLTALQDYINTNLVPTIDKISCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVCISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLklmkqiedkieeilskiyhieneiarikkligeapgglvprgshhhhhhsawshpqfek

NiV08(SEQ ID NO:8)

mysmqlascvtltlvllvnsQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSDMSQCTGSVMENYKTRLNGILTPIKGALEIYKNNTHDLVGDVRLAGVIMAGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVFTALQDYINTNLVPTIDKISCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDDSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLklmkqiedkieeilskiyhieneiarikkligeapgglvprgshhhhhhsawshpqfek

NiV09(SEQ ID NO:9)

mysmqlascvtltlvllvnsQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSQCTGSVMENYKTRLNGILTPIKGALEIYKNNTHDLVGDVRLAGVIMAGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVLTALQDYINTNLVPTIDKIPCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLklmkqiedkieeilskiyhieneiarikkligeapgglvprgshhhhhhsawshpqfek

NiV10(SEQ ID NO:10)

mysmqlascvtltlvllvnsQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSQCTGSVMENYKTRLNGILTPIKGALEIYKNGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVLTALQDYINTNLVPTIDKISCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLklmkqiedkieeilskiyhieneiarikkligeapgglvprgshhhhhhsawshpqfek

NiV11(SEQ ID NO:11)

mysmqlascvtltlvllvnsQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSQCTGSVMENYKTRLNGILTPIKGALEIYKNNTHDLVGDVRLAGVIMAGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVLTALQDWINTNLVPTIDKISCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLklmkqiedkieeilskiyhieneiarikkligeapgglvprgshhhhhhsawshpqfek

NiV12(SEQ ID NO:12)

mysmqlascvtltlvllvnsQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSQCTGSVMENYKTRLNGILTPIKGALEIYKNNTHDLVGDVRLAGVIMAGVAIGIATAAQITCGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVLTALQDYINTNLVPTIDKISCKQTELSLDLALSKYLSDLLFVFGPNLQDPCSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLklmkqiedkieeilskiyhieneiarikkligeapgglvprgshhhhhhsawshpqfek

NiV13(SEQ ID NO:13)

mysmqlascvtltlvllvnsQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSGCTGSVMENYKTRLNGILTPIKGALEIYKNNTHDLVGDVRLAGVIMAGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVLTALQDYINTNLVPTIDKISCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLklmkqiedkieeilskiyhieneiarikkligeapgglvprgshhhhhhsawshpqfek

NiV14(SEQ ID NO:14)

mysmqlascvtltlvllvnsQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSQCTGSVMENYKTRLNGILTPIKGALEIYKNNTHDLVGDVRLAGVIMAGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVLTALQDYINTNLVPTIGKIGCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLklmkqiedkieeilskiyhieneiarikkligeapgglvprgshhhhhhsawshpqfek

NiV15(SEQ ID NO:15)

mysmqlascvtltlvllvnsQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSDMSQCTGSVMENYKTRLNGILTPIKGALEIYKNNTHDLVGDVRLAGVIMAGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLCETAEKCVYVLTALQDYINTNLVPTIDKISCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDDSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLklmkqiedkieeilskiyhieneiarikkligeapgglvprgshhhhhhsawshpqfek

NiV16(SEQ ID NO:16)

mysmqlascvtltlvllvnsQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSQCTGSVMENYKTRLNGILTPIKGALEIYKNNTHDLVGDVRLAGVIMAGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVLTALQDYINTNLVPTIDKISCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTFQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLklmkqiedkieeilskiyhieneiarikkligeapgglvprgshhhhhhsawshpqfek

NiVop1(SEQ ID NO:17)

mysmqlascvtltlvllvnsQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSQCTGSVMENYKTRLNGILTPIKGALEIYKNNTHDLVGDVRLAGVcMAGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVFTALQDYINTNLVPTIDKISCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVcISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLKLMKQIEDKIEEILSKIYHIENEIARIKKLIGEAPGGLVPRGSHHHHHHSAWSHPQFEK

NiVop2(SEQ ID NO:18)

mysmqlascvtltlvllvnsQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSQCTGSVMENYKTRLNGILTPIKGALEIYKNNTHDcVGDVRLAGVcMAGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVFTALQDYINTNLVPTIDKISCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLKLMKQIEDKIEEILSKIYHIENEIARIKKLIGEAPGGLVPRGSHHHHHHSAWSHPQFEK

NiVop3(SEQ ID NO:19)

mysmqlascvtltlvllvnsQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSQCTGSVMENYKTRLNGILTPIKGALEIYKNNTgsgIMAGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVFTALQDYINTNLVPTIDKISCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLKLMKQIEDKIEEILSKIYHIENEIARIKKLIGEAPGGLVPRGSHHHHHHSAWSHPQFEK

NiVop4(SEQ ID NO:20)

mysmqlascvtltlvllvnsQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSQCTGSVMENYKTRLNGILTPIKGALEIYKNNTHDLVGDVRLAGVcMAGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVLTALQDYINTNLVPTIDKIPCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVcISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLKLMKQIEDKIEEILSKIYHIENEIARIKKLIGEAPGGLVPRGSHHHHHHSAWSHPQFEK

NiVop5(SEQ ID NO:21)

mysmqlascvtltlvllvnsQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSQCTGSVMENYKTRLNGILTPIKGALEIYKNNTHDcVGDVRLAGVcMAGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVLTALQDYINTNLVPTIDKIPCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLKLMKQIEDKIEEILSKIYHIENEIARIKKLIGEAPGGLVPRGSHHHHHHSAWSHPQFEK

NiVop6(SEQ ID NO:22)

mysmqlascvtltlvllvnsQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSQCTGSVMENYKTRLNGILTPIKGALEIYKNNTgsgIMAGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVLTALQDYINTNLVPTIDKIPCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLKLMKQIEDKIEEILSKIYHIENEIARIKKLIGEAPGGLVPRGSHHHHHHSAWSHPQFEK

NiVop7(SEQ ID NO:23)

mysmqlascvtltlvllvnsQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSQCTGSVMENYKTRLNGILTPIKGALEIYKNNTHDLVGDVRLAGVcMAGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVFTALQDYINTNLVPTIDKIPCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVcISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLKLMKQIEDKIEEILSKIYHIENEIARIKKLIGEAPGGLVPRGSHHHHHHSAWSHPQFEK

NiVop8(SEQ ID NO:24)

mysmqlascvtltlvllvnsQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSQCTGSVMENYKTRLNGILTPIKGALEIYKNNTHDcVGDVRLAGVcMAGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVFTALQDYINTNLVPTIDKIPCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLKLMKQIEDKIEEILSKIYHIENEIARIKKLIGEAPGGLVPRGSHHHHHHSAWSHPQFEK

NiVop9(SEQ ID NO:25)

mysmqlascvtltlvllvnsQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSQCTGSVMENYKTRLNGILTPIKGALEIYKNNTgsgIMAGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVFTALQDYINTNLVPTIDKIPCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLKLMKQIEDKIEEILSKIYHIENEIARIKKLIGEAPGGLVPRGSHHHHHHSAWSHPQFEK

NiVop12(SEQ ID NO:26)

mysmqlascvtltlvllvnsQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSQCTGSVMENYKTRLNGILTPIKGALEIYKNNTHDLVGDVRLAGVIMAGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVFTALQDYINTNLVPTIDKIpCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLKLMKQIEDKIEEILSKIYHIENEIARIKKLIGEAPGGLVPRGSHHHHHHSAWSHPQFEK

NiVop13(SEQ ID NO:27)

mysmqlascvtltlvllvnsQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSGCTGSVMENYKTRLNGILTPIKGALEIYKNNTHDLVGDVRLAGVIMAGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVFTALQDYINTNLVPTIDKIpCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLKLMKQIEDKIEEILSKIYHIENEIARIKKLIGEAPGGLVPRGSHHHHHHSAWSHPQFEK

NiVop14(SEQ ID NO:28)

mysmqlascvtltlvllvnsQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSGCTGSVMENYKTRLNGILTPIKGALEIYKNNTHDcVGDVRLAGVcMAGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVFTALQDYINTNLVPTIDKIPCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLKLMKQIEDKIEEILSKIYHIENEIARIKKLIGEAPGGLVPRGSHHHHHHSAWSHPQFEK

NiVop15(SEQ ID NO:29)

mysmqlascvtltlvllvnsQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSGCTGSVMENYKTRLNGILTPIKGALEIYKNNTHDcVGDVRLAGVcMAGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVFTALQDYINTNLVPTIDKISCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLKLMKQIEDKIEEILSKIYHIENEIARIKKLIGEAPGGLVPRGSHHHHHHSAWSHPQFEK

NiVop16(SEQ ID NO:30)

mysmqlascvtltlvllvnsQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSGCTGSVMENYKTRLNGILTPIKGALEIYKNNTHDcVGDVRLAGVcMAGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVLTALQDYINTNLVPTIDKISCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLKLMKQIEDKIEEILSKIYHIENEIARIKKLIGEAPGGLVPRGSHHHHHHSAWSHPQFEK

NiVop17(SEQ ID NO:31)

mysmqlascvtltlvllvnsQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSQCTGSVMENYKTRLNGILTPIKGALEIYKNNTHDcVGDVRLAGVcMAGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLCETAEKCVYVFTALQDYINTNLVPTIDKIPCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLKLMKQIEDKIEEILSKIYHIENEIARIKKLIGEAPGGLVPRGSHHHHHHSAWSHPQFEK

NiVop18(SEQ ID NO:32)

mysmqlascvtltlvllvnsQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSQCTGSVMENYKTRLNGILTPIKGALEIYKNNTHDcVGDVRLAGVcMAGVAIGIATAAQITCGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVFTALQDYINTNLVPTIDKIPCKQTELSLDLALSKYLSDLLFVFGPNLQDPCSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLKLMKQIEDKIEEILSKIYHIENEIARIKKLIGEAPGGLVPRGSHHHHHHSAWSHPQFEK

以上序列包括N端信号肽、NiV F胞外域、GCN4三聚结构域、凝血酶切割位点、HIS标签和Strep标签，以及区段之间的各种接头残基。

实施例2

NiV G多聚体

本实施例说明了包括NiV G胞外域的多聚体的免疫原的实施方式。

NiV G胞外域的N端连接到T4纤维蛋白三聚结构域，C端是his标签。设计了包括一个、两个或三个串联的G胞外域的构建体的不同版本。设计了另一多聚体，其包括两个G胞外域，一个在T4纤维蛋白三聚结构域(Fd)的一端(N和C端)。序列如下：

Fd-G(SEQ ID NO:34)

mysmqlascvtltlvllvnsQGSGYIPEAPRDGQAYVRKDGEWVLLSTFLGSGGGGGgvsnlvglpnniclqktsnqilkpklisytlpvvgqsgtcitdpllamdegyfayshlerigscsrgvskqriigvgevldrgdevpslfmtnvwtppnpntvyhcsavynnefyyvlcavstvgdpilnstywsgslmmtrlavkpksngggynqhqlalrsiekgrydkvmpygpsgikqgdtlyfpavgflvrtefkyndsncpitkcqyskpencrlsmgirpnshyilrsgllkynlsdgenpkvvfieisdqrlsigspskiydslgqpvfyqasfswdtmikfgdvltvnplvvnwrnntvisrpgqsqcprfntcpeicwegvyndaflidrinwisagvfldsnqtaenpvftvfkdneilyraqlasedtnaqktitncfllknkiwcislveiydtgdnvirpklfavkipeqctgglvprgshhhhhhsawshpqfek

Fd-GG(SEQ ID NO:35)

mysmqlascvtltlvllvnsQGSGYIPEAPRDGQAYVRKDGEWVLLSTFLGSGGGGGgvsnlvglpnniclqktsnqilkpklisytlpvvgqsgtcitdpllamdegyfayshlerigscsrgvskqriigvgevldrgdevpslfmtnvwtppnpntvyhcsavynnefyyvlcavstvgdpilnstywsgslmmtrlavkpksngggynqhqlalrsiekgrydkvmpygpsgikqgdtlyfpavgflvrtefkyndsncpitkcqyskpencrlsmgirpnshyilrsgllkynlsdgenpkvvfieisdqrlsigspskiydslgqpvfyqasfswdtmikfgdvltvnplvvnwrnntvisrpgqsqcprfntcpeicwegvyndaflidrinwisagvfldsnqtaenpvftvfkdneilyraqlasedtnaqktitncfllknkiwcislveiydtgdnvirpklfavkipeqctggGGGGgvsnlvglpnniclqktsnqilkpklisytlpvvgqsgtcitdpllamdegyfayshlerigscsrgvskqriigvgevldrgdevpslfmtnvwtppnpntvyhcsavynnefyyvlcavstvgdpilnstywsgslmmtrlavkpksngggynqhqlalrsiekgrydkvmpygpsgikqgdtlyfpavgflvrtefkyndsncpitkcqyskpencrlsmgirpnshyilrsgllkynlsdgenpkvvfieisdqrlsigspskiydslgqpvfyqasfswdtmikfgdvltvnplvvnwrnntvisrpgqsqcprfntcpeicwegvyndaflidrinwisagvfldsnqtaenpvftvfkdneilyraqlasedtnaqktitncfllknkiwcislveiydtgdnvirpklfavkipeqctgglvprgshhhhhhsawshpqfek

Fd-GGG(SEQ ID NO:36)

mysmqlascvtltlvllvnsQGSGYIPEAPRDGQAYVRKDGEWVLLSTFLGSGGGGGgvsnlvglpnniclqktsnqilkpklisytlpvvgqsgtcitdpllamdegyfayshlerigscsrgvskqriigvgevldrgdevpslfmtnvwtppnpntvyhcsavynnefyyvlcavstvgdpilnstywsgslmmtrlavkpksngggynqhqlalrsiekgrydkvmpygpsgikqgdtlyfpavgflvrtefkyndsncpitkcqyskpencrlsmgirpnshyilrsgllkynlsdgenpkvvfieisdqrlsigspskiydslgqpvfyqasfswdtmikfgdvltvnplvvnwrnntvisrpgqsqcprfntcpeicwegvyndaflidrinwisagvfldsnqtaenpvftvfkdneilyraqlasedtnaqktitncfllknkiwcislveiydtgdnvirpklfavkipeqctggGGGGgvsnlvglpnniclqktsnqilkpklisytlpvvgqsgtcitdpllamdegyfayshlerigscsrgvskqriigvgevldrgdevpslfmtnvwtppnpntvyhcsavynnefyyvlcavstvgdpilnstywsgslmmtrlavkpksngggynqhqlalrsiekgrydkvmpygpsgikqgdtlyfpavgflvrtefkyndsncpitkcqyskpencrlsmgirpnshyilrsgllkynlsdgenpkvvfieisdqrlsigspskiydslgqpvfyqasfswdtmikfgdvltvnplvvnwrnntvisrpgqsqcprfntcpeicwegvyndaflidrinwisagvfldsnqtaenpvftvfkdneilyraqlasedtnaqktitncfllknkiwcislveiydtgdnvirpklfavkipeqctggGGGGgvsnlvglpnniclqktsnqilkpklisytlpvvgqsgtcitdpllamdegyfayshlerigscsrgvskqriigvgevldrgdevpslfmtnvwtppnpntvyhcsavynnefyyvlcavstvgdpilnstywsgslmmtrlavkpksngggynqhqlalrsiekgrydkvmpygpsgikqgdtlyfpavgflvrtefkyndsncpitkcqyskpencrlsmgirpnshyilrsgllkynlsdgenpkvvfieisdqrlsigspskiydslgqpvfyqasfswdtmikfgdvltvnplvvnwrnntvisrpgqsqcprfntcpeicwegvyndaflidrinwisagvfldsnqtaenpvftvfkdneilyraqlasedtnaqktitncfllknkiwcislveiydtgdnvirpklfavkipeqctgglvprgshhhhhhsawshpqfek

G-Fd-G(SEQ ID NO:37)

mysmqlascvtltlvllvnsQEgvsnlvglpnniclqktsnqilkpklisytlpvvgqsgtcitdpllamdegyfayshlerigscsrgvskqriigvgevldrgdevpslfmtnvwtppnpntvyhcsavynnefyyvlcavstvgdpilnstywsgslmmtrlavkpksngggynqhqlalrsiekgrydkvmpygpsgikqgdtlyfpavgflvrtefkyndsncpitkcqyskpencrlsmgirpnshyilrsgllkynlsdgenpkvvfieisdqrlsigspskiydslgqpvfyqasfswdtmikfgdvltvnplvvnwrnntvisrpgqsqcprfntcpeicwegvyndaflidrinwisagvfldsnqtaenpvftvfkdneilyraqlasedtnaqktitncfllknkiwcislveiydtgdnvirpklfavkipeqctggGSGYIPEAPRDGQAYVRKDGEWVLLSTFLGSGGGGGgvsnlvglpnniclqktsnqilkpklisytlpvvgqsgtcitdpllamdegyfayshlerigscsrgvskqriigvgevldrgdevpslfmtnvwtppnpntvyhcsavynnefyyvlcavstvgdpilnstywsgslmmtrlavkpksngggynqhqlalrsiekgrydkvmpygpsgikqgdtlyfpavgflvrtefkyndsncpitkcqyskpencrlsmgirpnshyilrsgllkynlsdgenpkvvfieisdqrlsigspskiydslgqpvfyqasfswdtmikfgdvltvnplvvnwrnntvisrpgqsqcprfntcpeicwegvyndaflidrinwisagvfldsnqtaenpvftvfkdneilyraqlasedtnaqktitncfllknkiwcislveiydtgdnvirpklfavkipeqctgglvprgshhhhhhsawshpqfek

以上序列包括一个或更多个G胞外域、N端信号肽、HIS标签、Strep标签以及去除这两个标签的凝血酶裂解位点、三聚结构域和区段之间的各种接头残基。

Fd-G、Fd-GG、Fd-GGG和G-Fd-G在细胞中表达，并如以上实施例1中针对可溶性NiVF胞外域三聚体所讨论的那样纯化。每个构建体都被成功纯化。Fd-G和G-Fd-G构建体的表达水平分别为8和2.3mg/mL。

负染EM表明所有这些构建体形成多聚体。G-Fd和G-Fd-G多聚体的示例性负染EM图像如图4所示。

另外的NiV G胞外域多聚体是通过G胞外域与自组装铁蛋白纳米颗粒亚基的N端连接而构建的。该构建体的不同形式包括在G胞外域和铁蛋白亚基之间具有5、15、25或35个残基的甘氨酸-丝氨酸接头。设计了另外的多聚体，其包括连接至自组装二氧四氢蝶啶合酶纳米颗粒的亚基的N端的NiV G胞外域。产生了不同版本的构建体，包括在G胞外域和铁蛋白或二氧四氢蝶啶合酶亚基之间的5、15、25或35个残基的甘氨酸-丝氨酸接头。序列如下：

G-ln5-Fer(SEQ ID NO:38)

mysmqlascvtltlvllvnsqHHHHHHGSAWSHPQFEKGGLVPRGSGnsqrpqtegvsnlvglpnniclqktsnqilkpklisytlpvvgqsgtcitdpllamdegyfayshlerigscsrgvskqriigvgevldrgdevpslfmtnvwtppnpntvyhcsavynnefyyvlcavstvgdpilnstywsgslmmtrlavkpksngggynqhqlalrsiekgrydkvmpygpsgikqgdtlyfpavgflvrtefkyndsncpitkcqyskpencrlsmgirpnshyilrsgllkynlsdgenpkvvfieisdqrlsigspskiydslgqpvfyqasfswdtmikfgdvltvnplvvnwrnntvisrpgqsqcprfntcpeicwegvyndaflidrinwisagvfldsnqtaenpvftvfkdneilyraqlasedtnaqktitncfllknkiwcislveiydtgdnvirpklfavkipeqctgggSGGDIIKLLNEQVNKEMQSSNLYMSMSSWCYTHSLDGAGLFLFDHAAEEYEHAKKLIIFLNENNVPVQLTSISAPEHKFEGLTQIFQKAYEHEQHISESINNIVDHAIKSKDHATFNFLQWYVAEQHEEEVLFKDILDKIELIGNENHGLYLADQYVKGIAKSRKSGS

G-ln15-Fer(SEQ ID NO:39)

mysmqlascvtltlvllvnsqHHHHHHGSAWSHPQFEKGGLVPRGSGnsqrpqtegvsnlvglpnniclqktsnqilkpklisytlpvvgqsgtcitdpllamdegyfayshlerigscsrgvskqriigvgevldrgdevpslfmtnvwtppnpntvyhcsavynnefyyvlcavstvgdpilnstywsgslmmtrlavkpksngggynqhqlalrsiekgrydkvmpygpsgikqgdtlyfpavgflvrtefkyndsncpitkcqyskpencrlsmgirpnshyilrsgllkynlsdgenpkvvfieisdqrlsigspskiydslgqpvfyqasfswdtmikfgdvltvnplvvnwrnntvisrpgqsqcprfntcpeicwegvyndaflidrinwisagvfldsnqtaenpvftvfkdneilyraqlasedtnaqktitncfllknkiwcislveiydtgdnvirpklfavkipeqctgggSGGggsggSGGgDIIKLLNEQVNKEMQSSNLYMSMSSWCYTHSLDGAGLFLFDHAAEEYEHAKKLIIFLNENNVPVQLTSISAPEHKFEGLTQIFQKAYEHEQHISESINNIVDHAIKSKDHATFNFLQWYVAEQHEEEVLFKDILDKIELIGNENHGLYLADQYVKGIAKSRKSGS

G-ln25-Fer(SEQ ID NO:40)

mysmqlascvtltlvllvnsqHHHHHHGSAWSHPQFEKGGLVPRGSGnsqrpqtegvsnlvglpnniclqktsnqilkpklisytlpvvgqsgtcitdpllamdegyfayshlerigscsrgvskqriigvgevldrgdevpslfmtnvwtppnpntvyhcsavynnefyyvlcavstvgdpilnstywsgslmmtrlavkpksngggynqhqlalrsiekgrydkvmpygpsgikqgdtlyfpavgflvrtefkyndsncpitkcqyskpencrlsmgirpnshyilrsgllkynlsdgenpkvvfieisdqrlsigspskiydslgqpvfyqasfswdtmikfgdvltvnplvvnwrnntvisrpgqsqcprfntcpeicwegvyndaflidrinwisagvfldsnqtaenpvftvfkdneilyraqlasedtnaqktitncfllknkiwcislveiydtgdnvirpklfavkipeqctgggSGGggsggSGGggSGGggSGGgDIIKLLNEQVNKEMQSSNLYMSMSSWCYTHSLDGAGLFLFDHAAEEYEHAKKLIIFLNENNVPVQLTSISAPEHKFEGLTQIFQKAYEHEQHISESINNIVDHAIKSKDHATFNFLQWYVAEQHEEEVLFKDILDKIELIGNENHGLYLADQYVKGIAKSRKSGS

G-ln35-Fer(SEQ ID NO:41)

mysmqlascvtltlvllvnsqHHHHHHGSAWSHPQFEKGGLVPRGSGnsqrpqtegvsnlvglpnniclqktsnqilkpklisytlpvvgqsgtcitdpllamdegyfayshlerigscsrgvskqriigvgevldrgdevpslfmtnvwtppnpntvyhcsavynnefyyvlcavstvgdpilnstywsgslmmtrlavkpksngggynqhqlalrsiekgrydkvmpygpsgikqgdtlyfpavgflvrtefkyndsncpitkcqyskpencrlsmgirpnshyilrsgllkynlsdgenpkvvfieisdqrlsigspskiydslgqpvfyqasfswdtmikfgdvltvnplvvnwrnntvisrpgqsqcprfntcpeicwegvyndaflidrinwisagvfldsnqtaenpvftvfkdneilyraqlasedtnaqktitncfllknkiwcislveiydtgdnvirpklfavkipeqctgggSGGggsggSGGggSGGggSGGggSGGggSGGgDIIKLLNEQVNKEMQSSNLYMSMSSWCYTHSLDGAGLFLFDHAAEEYEHAKKLIIFLNENNVPVQLTSISAPEHKFEGLTQIFQKAYEHEQHISESINNIVDHAIKSKDHATFNFLQWYVAEQHEEEVLFKDILDKIELIGNENHGLYLADQYVKGIAKSRKSGS

G-LS(SEQ ID NO:42)

mysmqlascvtltlvllvnsqHHHHHHGSAWSHPQFEKGGLVPRGSGnsqrpqtegvsnlvglpnniclqktsnqilkpklisytlpvvgqsgtcitdpllamdegyfayshlerigscsrgvskqriigvgevldrgdevpslfmtnvwtppnpntvyhcsavynnefyyvlcavstvgdpilnstywsgslmmtrlavkpksngggynqhqlalrsiekgrydkvmpygpsgikqgdtlyfpavgflvrtefkyndsncpitkcqyskpencrlsmgirpnshyilrsgllkynlsdgenpkvvfieisdqrlsigspskiydslgqpvfyqasfswdtmikfgdvltvnplvvnwrnntvisrpgqsqcprfntcpeicwegvyndaflidrinwisagvfldsnqtaenpvftvfkdneilyraqlasedtnaqktitncfllknkiwcislveiydtgdnvirpklfavkipeqctgggsgggsgggsMQIYEGKLTAEGLRFGIVASRFNHALVDRLVEGAIDCIVRHGGREEDITLVRVPGSWEIPVAAGELARKEDIDAVIAIGVLIRGATPHFDYIASEVSKGLADLSLELRKPITFGVITADTLEQAIERAGTKHGNKGWEAALSAIEMANLFKSLR

以上序列包括一个或更多个G胞外域、自组装纳米颗粒亚基、N端信号肽、HIS标签、Strep标签、去除两个标签的凝血酶切割位点以及区段之间的各种接头残基。

G-In5-Fer、G-In15-Fer、G-In25-Fer、G-In35-Fer和G-LS构建体在细胞中表达，并按上述实施例1中可溶性NiV F胞外域三聚体的方法纯化。每个构建体成功地纯化为多聚纳米颗粒。

负染EM显示所有这些构建体均自组装成多聚体纳米颗粒。G-In5-Fer、G-In15-Fer和G-In25-Fer多聚体的示例性负染色EM图像如图5A-5C所示。

用G-Fd、G-Fd-G、G-ln5-Fer、G-ln15-Fer和G-ln35-Fer多聚体进行免疫测定。基本上如实施例1中所述进行测定。使用图6A所示的时间表，在Alum中用5μg多聚体免疫CB6F1/J小鼠。使用Octet结合测定法检测获自免疫小鼠的血清与单体NiV G的结合(图6B)。NiV G连接到传感器，检测来自指定免疫的血清的结合。还通过NiV假病毒中和测定法(图6C)评估免疫血清，其显示获自用多聚NiV G构建体处理的动物的免疫血清中和NiV。因此，在动物模型中用可溶性多聚体NiV G构建体免疫引发中和免疫应答。

实施例3

NiV F-G胞外域嵌合体的多聚体

本实施例说明了包括NiV F和G胞外域的多聚体的免疫原的实施方式。

图7A示出了包含在NiV F-G多聚体中的嵌合蛋白的结构。评估了嵌合多聚体的多种形式，包括：

·preF-TD-G：融合前F胞外域(例如NiVop08)融合至C端三聚结构域(例如GCN4、Fd或GCN4和Fd)，再融合至G胞外域

·G-preF-TD：G胞外域融合至融合前F胞外域(例如NiVop08)，再融合至C端三聚结构域(例如GCN4、Fd或GCN4和Fd)

作为对照，还产生了融合后构建体：

·postF-TD-G：融合后F胞外域(例如NiV06)融合至C端三聚结构域(例如GCN4、Fd或GCN4和Fd)，再融合至G胞外域序列如下所示：

NiVop08–TD(GCN4-Fd)-G(SEQ ID NO:43)

mysmqlascvtltlvllvnsQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSQCTGSVMENYKTRLNGILTPIKGALEIYKNNTHDCVGDVRLAGVCMAGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVFTALQDYINTNLVPTIDKIPCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLKLMKQIEDKIEEILSKIYHIENEIARIKKLIGEAPGSGYIPEAPRDGQAYVRKDGEWVLLSTFLGSGGGGGgvsnlvglpnniclqktsnqilkpklisytlpvvgqsgtcitdpllamdegyfayshlerigscsrgvskqriigvgevldrgdevpslfmtnvwtppnpntvyhcsavynnefyyvlcavstvgdpilnstywsgslmmtrlavkpksngggynqhqlalrsiekgrydkvmpygpsgikqgdtlyfpavgflvrtefkyndsncpitkcqyskpencrlsmgirpnshyilrsgllkynlsdgenpkvvfieisdqrlsigspskiydslgqpvfyqasfswdtmikfgdvltvnplvvnwrnntvisrpgqsqcprfntcpeicwegvyndaflidrinwisagvfldsnqtaenpvftvfkdneilyraqlasedtnaqktitncfllknkiwcislveiydtgdnvirpklfavkipeqctgglvprgshhhhhhsawshpqfek

G–NiVop08-TD(GCN4-Fd)(SEQ ID NO:44)

MysmqlascvtltlvllvnsqrpqtegvsnlvglpnniclqktsnqilkpklisytlpvvgqsgtcitdpllamdegyfayshlerigscsrgvskqriigvgevldrgdevpslfmtnvwtppnpntvyhcsavynnefyyvlcavstvgdpilnstywsgslmmtrlavkpksngggynqhqlalrsiekgrydkvmpygpsgikqgdtlyfpavgflvrtefkyndsncpitkcqyskpencrlsmgirpnshyilrsgllkynlsdgenpkvvfieisdqrlsigspskiydslgqpvfyqasfswdtmikfgdvltvnplvvnwrnntvisrpgqsqcprfntcpeicwegvyndaflidrinwisagvfldsnqtaenpvftvfkdneilyraqlasedtnaqktitncfllknkiwcislveiydtgdnvirpklfavkipeqctgggQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSQCTGSVMENYKTRLNGILTPIKGALEIYKNNTHDCVGDVRLAGVCMAGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVFTALQDYINTNLVPTIDKIPCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLKLMKQIEDKIEEILSKIYHIENEIARIKKLIGEAPGSGYIPEAPRDGQAYVRKDGEWVLLSTFLGSLVPRGSHHHHHHSAWSHPQFEK

NiV06-TD(GCN4-Fd)-G(SEQ ID NO:45)

MysmqlascvtltlvllvnsQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSQCTGSVMENYKTRLNGILTPIKGALEIYKNGGSGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVLTALQDYINTNLVPTIDKISCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLKLMKQIEDKIEEILSKIYHIENEIARIKKLIGEAPGSGYIPEAPRDGQAYVRKDGEWVLLSTFLGSGGGGGgvsnlvglpnniclqktsnqilkpklisytlpvvgqsgtcitdpllamdegyfayshlerigscsrgvskqriigvgevldrgdevpslfmtnvwtppnpntvyhcsavynnefyyvlcavstvgdpilnstywsgslmmtrlavkpksngggynqhqlalrsiekgrydkvmpygpsgikqgdtlyfpavgflvrtefkyndsncpitkcqyskpencrlsmgirpnshyilrsgllkynlsdgenpkvvfieisdqrlsigspskiydslgqpvfyqasfswdtmikfgdvltvnplvvnwrnntvisrpgqsqcprfntcpeicwegvyndaflidrinwisagvfldsnqtaenpvftvfkdneilyraqlasedtnaqktitncfllknkiwcislveiydtgdnvirpklfavkipeqctgglvprgshhhhhhsawshpqfek

NiV06-TD(GCN4-Fd)-GG(SEQ ID NO:46)

MysmqlascvtltlvllvnsQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSQCTGSVMENYKTRLNGILTPIKGALEIYKNGGSGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVLTALQDYINTNLVPTIDKISCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLKLMKQIEDKIEEILSKIYHIENEIARIKKLIGEAPGSGYIPEAPRDGQAYVRKDGEWVLLSTFLGSGGGGGgvsnlvglpnniclqktsnqilkpklisytlpvvgqsgtcitdpllamdegyfayshlerigscsrgvskqriigvgevldrgdevpslfmtnvwtppnpntvyhcsavynnefyyvlcavstvgdpilnstywsgslmmtrlavkpksngggynqhqlalrsiekgrydkvmpygpsgikqgdtlyfpavgflvrtefkyndsncpitkcqyskpencrlsmgirpnshyilrsgllkynlsdgenpkvvfieisdqrlsigspskiydslgqpvfyqasfswdtmikfgdvltvnplvvnwrnntvisrpgqsqcprfntcpeicwegvyndaflidrinwisagvfldsnqtaenpvftvfkdneilyraqlasedtnaqktitncfllknkiwcislveiydtgdnvirpklfavkipeqctggGGGGgvsnlvglpnniclqktsnqilkpklisytlpvvgqsgtcitdpllamdegyfayshlerigscsrgvskqriigvgevldrgdevpslfmtnvwtppnpntvyhcsavynnefyyvlcavstvgdpilnstywsgslmmtrlavkpksngggynqhqlalrsiekgrydkvmpygpsgikqgdtlyfpavgflvrtefkyndsncpitkcqyskpencrlsmgirpnshyilrsgllkynlsdgenpkvvfieisdqrlsigspskiydslgqpvfyqasfswdtmikfgdvltvnplvvnwrnntvisrpgqsqcprfntcpeicwegvyndaflidrinwisagvfldsnqtaenpvftvfkdneilyraqlasedtnaqktitncfllknkiwcislveiydtgdnvirpklfavkipeqctgglvprgshhhhhhsawshpqfek

NiVop08-TD(GCN4-Fd)-GG(SEQ ID NO:47)

MysmqlascvtltlvllvnsQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSQCTGSVMENYKTRLNGILTPIKGALEIYKNNTHDCVGDVRLAGVCMAGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVFTALQDYINTNLVPTIDKIPCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLKLMKQIEDKIEEILSKIYHIENEIARIKKLIGEAPGSGYIPEAPRDGQAYVRKDGEWVLLSTFLGSGGGGGgvsnlvglpnniclqktsnqilkpklisytlpvvgqsgtcitdpllamdegyfayshlerigscsrgvskqriigvgevldrgdevpslfmtnvwtppnpntvyhcsavynnefyyvlcavstvgdpilnstywsgslmmtrlavkpksngggynqhqlalrsiekgrydkvmpygpsgikqgdtlyfpavgflvrtefkyndsncpitkcqyskpencrlsmgirpnshyilrsgllkynlsdgenpkvvfieisdqrlsigspskiydslgqpvfyqasfswdtmikfgdvltvnplvvnwrnntvisrpgqsqcprfntcpeicwegvyndaflidrinwisagvfldsnqtaenpvftvfkdneilyraqlasedtnaqktitncfllknkiwcislveiydtgdnvirpklfavkipeqctggGGGGgvsnlvglpnniclqktsnqilkpklisytlpvvgqsgtcitdpllamdegyfayshlerigscsrgvskqriigvgevldrgdevpslfmtnvwtppnpntvyhcsavynnefyyvlcavstvgdpilnstywsgslmmtrlavkpksngggynqhqlalrsiekgrydkvmpygpsgikqgdtlyfpavgflvrtefkyndsncpitkcqyskpencrlsmgirpnshyilrsgllkynlsdgenpkvvfieisdqrlsigspskiydslgqpvfyqasfswdtmikfgdvltvnplvvnwrnntvisrpgqsqcprfntcpeicwegvyndaflidrinwisagvfldsnqtaenpvftvfkdneilyraqlasedtnaqktitncfllknkiwcislveiydtgdnvirpklfavkipeqctgglvprgshhhhhhsawshpqfek

NiV06-TD(GCN4-Fd)-GGG(SEQ ID NO:48)

MysmqlascvtltlvllvnsQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSQCTGSVMENYKTRLNGILTPIKGALEIYKNGGSGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVLTALQDYINTNLVPTIDKISCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLKLMKQIEDKIEEILSKIYHIENEIARIKKLIGEAPGSGYIPEAPRDGQAYVRKDGEWVLLSTFLGSGGGGGgvsnlvglpnniclqktsnqilkpklisytlpvvgqsgtcitdpllamdegyfayshlerigscsrgvskqriigvgevldrgdevpslfmtnvwtppnpntvyhcsavynnefyyvlcavstvgdpilnstywsgslmmtrlavkpksngggynqhqlalrsiekgrydkvmpygpsgikqgdtlyfpavgflvrtefkyndsncpitkcqyskpencrlsmgirpnshyilrsgllkynlsdgenpkvvfieisdqrlsigspskiydslgqpvfyqasfswdtmikfgdvltvnplvvnwrnntvisrpgqsqcprfntcpeicwegvyndaflidrinwisagvfldsnqtaenpvftvfkdneilyraqlasedtnaqktitncfllknkiwcislveiydtgdnvirpklfavkipeqctggGGGGgvsnlvglpnniclqktsnqilkpklisytlpvvgqsgtcitdpllamdegyfayshlerigscsrgvskqriigvgevldrgdevpslfmtnvwtppnpntvyhcsavynnefyyvlcavstvgdpilnstywsgslmmtrlavkpksngggynqhqlalrsiekgrydkvmpygpsgikqgdtlyfpavgflvrtefkyndsncpitkcqyskpencrlsmgirpnshyilrsgllkynlsdgenpkvvfieisdqrlsigspskiydslgqpvfyqasfswdtmikfgdvltvnplvvnwrnntvisrpgqsqcprfntcpeicwegvyndaflidrinwisagvfldsnqtaenpvftvfkdneilyraqlasedtnaqktitncfllknkiwcislveiydtgdnvirpklfavkipeqctggGGGGgvsnlvglpnniclqktsnqilkpklisytlpvvgqsgtcitdpllamdegyfayshlerigscsrgvskqriigvgevldrgdevpslfmtnvwtppnpntvyhcsavynnefyyvlcavstvgdpilnstywsgslmmtrlavkpksngggynqhqlalrsiekgrydkvmpygpsgikqgdtlyfpavgflvrtefkyndsncpitkcqyskpencrlsmgirpnshyilrsgllkynlsdgenpkvvfieisdqrlsigspskiydslgqpvfyqasfswdtmikfgdvltvnplvvnwrnntvisrpgqsqcprfntcpeicwegvyndaflidrinwisagvfldsnqtaenpvftvfkdneilyraqlasedtnaqktitncfllknkiwcislveiydtgdnvirpklfavkipeqctgglvprgshhhhhhsawshpqfek

NiVop08-TD(GCN4-Fd)-GGG(SEQ ID NO:49)

MysmqlascvtltlvllvnsQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSQCTGSVMENYKTRLNGILTPIKGALEIYKNNTHDCVGDVRLAGVCMAGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVFTALQDYINTNLVPTIDKIPCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLKLMKQIEDKIEEILSKIYHIENEIARIKKLIGEAPGSGYIPEAPRDGQAYVRKDGEWVLLSTFLGSGGGGGgvsnlvglpnniclqktsnqilkpklisytlpvvgqsgtcitdpllamdegyfayshlerigscsrgvskqriigvgevldrgdevpslfmtnvwtppnpntvyhcsavynnefyyvlcavstvgdpilnstywsgslmmtrlavkpksngggynqhqlalrsiekgrydkvmpygpsgikqgdtlyfpavgflvrtefkyndsncpitkcqyskpencrlsmgirpnshyilrsgllkynlsdgenpkvvfieisdqrlsigspskiydslgqpvfyqasfswdtmikfgdvltvnplvvnwrnntvisrpgqsqcprfntcpeicwegvyndaflidrinwisagvfldsnqtaenpvftvfkdneilyraqlasedtnaqktitncfllknkiwcislveiydtgdnvirpklfavkipeqctggGGGGgvsnlvglpnniclqktsnqilkpklisytlpvvgqsgtcitdpllamdegyfayshlerigscsrgvskqriigvgevldrgdevpslfmtnvwtppnpntvyhcsavynnefyyvlcavstvgdpilnstywsgslmmtrlavkpksngggynqhqlalrsiekgrydkvmpygpsgikqgdtlyfpavgflvrtefkyndsncpitkcqyskpencrlsmgirpnshyilrsgllkynlsdgenpkvvfieisdqrlsigspskiydslgqpvfyqasfswdtmikfgdvltvnplvvnwrnntvisrpgqsqcprfntcpeicwegvyndaflidrinwisagvfldsnqtaenpvftvfkdneilyraqlasedtnaqktitncfllknkiwcislveiydtgdnvirpklfavkipeqctggGGGGgvsnlvglpnniclqktsnqilkpklisytlpvvgqsgtcitdpllamdegyfayshlerigscsrgvskqriigvgevldrgdevpslfmtnvwtppnpntvyhcsavynnefyyvlcavstvgdpilnstywsgslmmtrlavkpksngggynqhqlalrsiekgrydkvmpygpsgikqgdtlyfpavgflvrtefkyndsncpitkcqyskpencrlsmgirpnshyilrsgllkynlsdgenpkvvfieisdqrlsigspskiydslgqpvfyqasfswdtmikfgdvltvnplvvnwrnntvisrpgqsqcprfntcpeicwegvyndaflidrinwisagvfldsnqtaenpvftvfkdneilyraqlasedtnaqktitncfllknkiwcislveiydtgdnvirpklfavkipeqctgglvprgshhhhhhsawshpqfek

G-NiV06-TD(GCN4-Fd)(SEQ ID NO:50)

MysmqlascvtltlvllvnsQrpqtegvsnlvglpnniclqktsnqilkpklisytlpvvgqsgtcitdpllamdegyfayshlerigscsrgvskqriigvgevldrgdevpslfmtnvwtppnpntvyhcsavynnefyyvlcavstvgdpilnstywsgslmmtrlavkpksngggynqhqlalrsiekgrydkvmpygpsgikqgdtlyfpavgflvrtefkyndsncpitkcqyskpencrlsmgirpnshyilrsgllkynlsdgenpkvvfieisdqrlsigspskiydslgqpvfyqasfswdtmikfgdvltvnplvvnwrnntvisrpgqsqcprfntcpeicwegvyndaflidrinwisagvfldsnqtaenpvftvfkdneilyraqlasedtnaqktitncfllknkiwcislveiydtgdnvirpklfavkipeqctgggGGQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSQCTGSVMENYKTRLNGILTPIKGALEIYKNGGSGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVLTALQDYINTNLVPTIDKISCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLklmkqiedkieeilskiyhieneiarikkligeapgglvprgshhhhhhsawshpqfek

G-NiVop08-TD(GCN4-Fd)(SEQ ID NO:51)

MysmqlascvtltlvllvnsQrpqtegvsnlvglpnniclqktsnqilkpklisytlpvvgqsgtcitdpllamdegyfayshlerigscsrgvskqriigvgevldrgdevpslfmtnvwtppnpntvyhcsavynnefyyvlcavstvgdpilnstywsgslmmtrlavkpksngggynqhqlalrsiekgrydkvmpygpsgikqgdtlyfpavgflvrtefkyndsncpitkcqyskpencrlsmgirpnshyilrsgllkynlsdgenpkvvfieisdqrlsigspskiydslgqpvfyqasfswdtmikfgdvltvnplvvnwrnntvisrpgqsqcprfntcpeicwegvyndaflidrinwisagvfldsnqtaenpvftvfkdneilyraqlasedtnaqktitncfllknkiwcislveiydtgdnvirpklfavkipeqctggggsggggQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSQCTGSVMENYKTRLNGILTPIKGALEIYKNNTHDCVGDVRLAGVCMAGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVFTALQDYINTNLVPTIDKIPCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLKLMKQIEDKIEEILSKIYHIENEIARIKKLIGEAPGSGYIPEAPRDGQAYVRKDGEWVLLSTFLGSLVPRGSHHHHHHSAWSHPQFEK

NiVop08-GCN4-G(SEQ ID NO:59)

MYSMQLASCVTLTLVLLVNSQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSQCTGSVMENYKTRLNGILTPIKGALEIYKNNTHDCVGDVRLAGVCMAGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVFTALQDYINTNLVPTIDKIPCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLKLMKQIEDKIEEILSKIYHIENEIARIKKLIGEAPGSGGGGGGVSNLVGLPNNICLQKTSNQILKPKLISYTLPVVGQSGTCITDPLLAMDEGYFAYSHLERIGSCSRGVSKQRIIGVGEVLDRGDEVPSLFMTNVWTPPNPNTVYHCSAVYNNEFYYVLCAVSTVGDPILNSTYWSGSLMMTRLAVKPKSNGGGYNQHQLALRSIEKGRYDKVMPYGPSGIKQGDTLYFPAVGFLVRTEFKYNDSNCPITKCQYSKPENCRLSMGIRPNSHYILRSGLLKYNLSDGENPKVVFIEISDQRLSIGSPSKIYDSLGQPVFYQASFSWDTMIKFGDVLTVNPLVVNWRNNTVISRPGQSQCPRFNTCPEICWEGVYNDAFLIDRINWISAGVFLDSNQTAENPVFTVFKDNEILYRAQLASEDTNAQKTITNCFLLKNKIWCISLVEIYDTGDNVIRPKLFAVKIPEQCTGGLVPRGSHHHHHHSAWSHPQFEK

NiVop08-Fd-G(SEQ ID NO:60)

MYSMQLASCVTLTLVLLVNSQGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSQCTGSVMENYKTRLNGILTPIKGALEIYKNNTHDCVGDVRLAGVCMAGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVFTALQDYINTNLVPTIDKIPCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLGSGYIPEAPRDGQAYVRKDGEWVLLSTFLGSGGGGGGVSNLVGLPNNICLQKTSNQILKPKLISYTLPVVGQSGTCITDPLLAMDEGYFAYSHLERIGSCSRGVSKQRIIGVGEVLDRGDEVPSLFMTNVWTPPNPNTVYHCSAVYNNEFYYVLCAVSTVGDPILNSTYWSGSLMMTRLAVKPKSNGGGYNQHQLALRSIEKGRYDKVMPYGPSGIKQGDTLYFPAVGFLVRTEFKYNDSNCPITKCQYSKPENCRLSMGIRPNSHYILRSGLLKYNLSDGENPKVVFIEISDQRLSIGSPSKIYDSLGQPVFYQASFSWDTMIKFGDVLTVNPLVVNWRNNTVISRPGQSQCPRFNTCPEICWEGVYNDAFLIDRINWISAGVFLDSNQTAENPVFTVFKDNEILYRAQLASEDTNAQKTITNCFLLKNKIWCISLVEIYDTGDNVIRPKLFAVKIPEQCTGGLVPRGSHHHHHHSAWSHPQFEK

上述序列包括F和G胞外域、N端信号肽、HIS标签、Strep标签和去除两个标签的凝血酶裂解位点，以及区段之间的各种接头残基。

如上关于实施例1中的可溶性NiV F胞外域三聚体所述，将NiVop08-TD-G(SEQ IDNO:43)、G-NiVop08-T(SEQ ID NO:44)和NiV06-TD-G(SEQ ID NO:45)构建体在细胞中表达并如上所述纯化。还如上所述在细胞中表达并基于细胞纯化了基于NiVop08的其他构建体，其包括具有GCN4或Fd的三聚结构域(但不同时包含两者)，并且如上文针对实施例1中的可溶性NiV F胞外域三聚体所讨论的那样纯化。每个构建体均成功地纯化为嵌合多聚体。此外，负染EM表明所有这些构建体均形成多聚体。示例性负染EM图像显示如图7B和7C所示。这些EM评估表明，前F构建体含有融合前形式的病毒融合蛋白，并且该分子在F-TD-G结构的尾部末端和GF-TD的头部附近具有三个额外的圆形G结构域构造(箭头显示实例)。由于尾部具有柔性，因此G位置存在一些变化。

用F-G嵌合多聚体和本文所述的其他构建体进行免疫测定。基本上按照实施例1所述进行免疫测定。CB6F1/J小鼠用Alum中的10μg总蛋白进行免疫接种(对于单免疫原测定，为10g，对于包括两种免疫原的免疫，各为5μg)，使用图8A中所示的时间表进行免疫。使用Octet结合测定法检测获自免疫小鼠的血清与融合前F胞外域三聚体(NiVop08)、融合后F胞外域三聚体(NiV06)或单体NiV G的结合(参见图8A-8C)。还通过NiV假病毒中和测定法(图8E)评估免疫血清，该测定显示获自用多聚NiV F-G构建体处理的动物的免疫血清中和NiV。

实施例4

雪貂模型中的RNA和蛋白免疫

本实施例描述了用几种公开的NiV免疫原免疫雪貂的结果。

根据图9A和9B所示的时间表在16个不同组中用基于蛋白或RNA平台的preF、postF、G六聚体或preF/G嵌合体免疫原对雪貂进行免疫。使用的免疫原是：

(1)preF：用编码具有NiVop08胞外域取代(L104C-I114C，L172F，S191P)的全长NiVF的10μg mRNA进行免疫。

(2)preF：用编码具有NiVop08胞外域取代(L104C-I114C，L172F，S191P)的全长NiVF的30μg mRNA免疫。

(3)preF：用编码具有NiVop08胞外域取代(L104C-I114C，L172F，S191P)的全长NiVF的100μg mRNA进行免疫。

(4)preF：用10μg纯化的可溶性NiVop08蛋白免疫。

(5)postF：用编码具有NiV06胞外域取代(Δ100-116，残基N99-G117通过GGS接头连接)的全长NiV F的10μgmRNA进行免疫。

(6)postF：用编码具有NiV06胞外域取代(Δ100-116，残基N99-G117通过GGS接头连接)的全长NiV F的30μg mRNA免疫。

(7)postF：用编码具有NiV06胞外域取代(Δ100-116，残基N99-G117通过GGS接头连接)的全长NiV F的100μg mRNA进行免疫。

(8)postF：用10μg纯化的可溶性NiV06蛋白免疫。

(9)可溶性G六聚体：用10μg编码G-Fd-G(SEQ ID NO:37)的mRNA免疫。

(10)可溶性G六聚体：用30μg编码G-Fd-G(SEQ ID NO:37)的mRNA免疫。

(11)可溶性G六聚体：用100μg编码G-Fd-G(SEQ ID NO:37)的mRNA免疫。

(12)可溶性G六聚体：用10μg纯化的可溶性三聚G-Fd-G(SEQ ID NO:37)蛋白免疫。

(13)可溶性preF/G嵌合体：用10μg编码NiVop08–TD(GCN4-Fd)-G(SEQ ID NO:43)的mRNA免疫。

(14)可溶性preF/G嵌合体：用30μg编码NiVop08–TD(GCN4-Fd)-G(SEQ ID NO:43)的mRNA免疫。

(15)可溶性preF/G嵌合体：用100μg编码NiVop08–TD(GCN4-Fd)-G(SEQ ID NO:43)的mRNA免疫。

(16)可溶性preF/G嵌合体：用10μg纯化的可溶性三聚NiVop08–TD(GCN4-Fd)-G(SEQ ID NO:43)蛋白进行免疫。

如上所述进行蛋白免疫。基本上如先前所述，使用脂质封装的mRNA免疫平台，用编码新免疫原的mRNA进行RNA免疫(参见Roth et al.,“A Modified mRNA VaccineTargeting Immunodominant NS Epitopes Protects Against Dengue Virus Infectionin HLA Class I Transgenic Mice,”Frot Immunol.,June 21,2019,Vol.10,Article1424；and Jagger et al.,J Infect Dis,“Protective Efficacy of Nucleic AcidVaccines Against Transmission of Zika Virus During Pregnancy in Mice,”jiz338,Jul 1,2019)。

在多个时间点从经免疫的动物收集血清。使用上述假病毒中和测定法评估第二次给药后三周和六周的血清中的NiV中和(图9C和9D)。

使用preF、preF/G嵌合体和G-六聚体免疫原在10μg和100μg m RNA免疫条件下通过血清进行活NiV细胞感染的体外病毒中和试验(VNT)(图10)。如图所示，获自每种免疫条件的血清在体外中和活NiV细胞感染。

将假病毒中和分析的结果与VNT分析的结果进行比较，以确定免疫血清是否以相似的程度中和活NiV和假NiV。获自preF、preF/G嵌合体和G-六聚体免疫条件的血清对NiV假病毒的中和与同一血清在VNT分析中对细胞的活NiV感染的中和密切相关。图11示出了示例性线性回归图，其描绘了活NiV和假NiV中和的相关性。

实施例5

免疫原热稳定性

本实施例提供了用于确定preF、postF、preF/G嵌合体和G-六聚体免疫原的热稳定性的测定结果。

三种单独的测定法用于探索这些免疫原的热稳定性：差示扫描量热法(DSC)、内在荧光光谱分析和动态光散射(DLS)。DSC可以检测所有热诱导的转变，而其他技术则可以将这些转变解释为分子中的构象或胶体变化。对于除PostF以外的所有蛋白，初始热事件均与三级结构变化和/或聚集有关。下表提供了使用DSC、固有荧光和DLS分析为PreF(NiVop08)、PostF(NiV06)、HexG(G-Fd-G，SEQ ID NO:37)和PreF-G(NiVop08–TD-G，SEQ ID NO：43)免疫原鉴定的不同热转变的转变中点(T

ND：使用标准分析参数未检测到转变。

实施例6

免疫原比较：信号序列和跨膜与可溶性mRNA

本实施例描述了用于在动物模型中引发针对尼帕病毒的免疫应答的不同免疫原变体的比较。评估的变量包括融合前稳定vs.野生型(WT)NiV F、三聚体、六聚体和四聚体(带柄)NiV G、跨膜(TM)vs可溶性/分泌NiV F和G、信号序列(IL-2信号序列或天然NiV信号序列)以及mRNA vs.蛋白免疫(参见图12A)。包括茎部和头部区域的天然G胞外域形成四聚体(类似于获批兽用的Hendra G疫苗)。

如上所述进行蛋白和mRNA免疫，并评估从免疫动物收集的血清的NiV preF和G结合。结果(图12B和12C)显示，用融合前稳定的NiV F免疫增加对pre-F结合抗体的引发，信号序列或分泌vs跨膜条件无明显影响，三聚G膜锚定的免疫原性比分泌的六聚G略强，G-六聚体免疫原的免疫原性比包括柄的四聚体G高。

实施例7

小鼠模型中的RNA和蛋白免疫

本实施例描述了用于在小鼠模型中引发针对尼帕病毒的免疫应答的不同免疫原和剂量的比较。preF(NiVop08)、postF(NiV06)、G-六聚体(也称为hexG；G-Fd-G，SEQ ID NO:37)和PreF-G(NiVop08-TD-G，SEQ ID NO:43)免疫原使用如上所述的基于mRNA和基于蛋白的免疫方案进行评估，并评估从免疫动物收集的血清的NiV preF和G结合。免疫方案和总结在图13A和13B中提供。结果(图13C和13D)表明基于mRNA和蛋白的免疫均引起小鼠的免疫应答。

显而易见的是，在不背离所描述的实施方式的精神的情况下，可以改变或修改所描述的方法或组合物的精确详细信息。我们要求落入所附权利要求的范围和精神内的所有此类修改和变型。

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<110> 美国政府（由卫生和人类服务部的部长所代表）

<120> 尼帕病毒免疫原及其用途

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<150> US 62/714,230

<151> 2018-08-03

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Val Leu Phe Ala Asn Cys Ile Ser Val Thr Cys Gln Cys Gln Thr Thr

370 375 380

Gly Arg Ala Ile Ser Gln Ser Gly Glu Gln Thr Leu Leu Met Ile Asp

385 390 395 400

Asn Thr Thr Cys Pro Thr Ala Val Leu Gly Asn Val Ile Ile Ser Leu

405 410 415

Gly Lys Tyr Leu Gly Ser Val Asn Tyr Asn Ser Glu Gly Ile Ala Ile

420 425 430

Gly Pro Pro Val Phe Thr Asp Lys Val Asp Ile Ser Ser Gln Ile Ser

435 440 445

Ser Met Asn Gln Ser Leu Gln Gln Ser Lys Asp Tyr Ile Lys Glu Ala

450 455 460

Gln Arg Leu Leu Asp Thr Val Asn Pro Ser Leu Lys Leu Met Lys Gln

465 470 475 480

Ile Glu Asp Lys Ile Glu Glu Ile Leu Ser Lys Ile Tyr His Ile Glu

485 490 495

Asn Glu Ile Ala Arg Ile Lys Lys Leu Ile Gly Glu Ala Pro Gly Gly

500 505 510

Leu Val Pro Arg Gly Ser His His His His His His Ser Ala Trp Ser

515 520 525

His Pro Gln Phe Glu Lys

530

<210> 5

<211> 543

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 5

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Gly Ile Leu His Tyr Glu Lys Leu Ser Lys Ile

20 25 30

Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro

35 40 45

Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn Val Ser Asn Met

50 55 60

Ser Gln Cys Thr Gly Ser Val Met Glu Asn Tyr Lys Thr Arg Leu Asn

65 70 75 80

Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile Tyr Lys Asn Asn

85 90 95

Thr His Asp Cys Val Gly Asp Val Arg Leu Ala Gly Val Cys Met Ala

100 105 110

Gly Val Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile Thr Ala Gly Val

115 120 125

Ala Leu Tyr Glu Ala Met Lys Asn Ala Asp Asn Ile Asn Lys Leu Lys

130 135 140

Ser Ser Ile Glu Ser Thr Asn Glu Ala Val Val Lys Leu Gln Glu Thr

145 150 155 160

Ala Glu Lys Thr Val Tyr Val Leu Thr Ala Leu Gln Asp Tyr Ile Asn

165 170 175

Thr Asn Leu Val Pro Thr Ile Asp Lys Ile Ser Cys Lys Gln Thr Glu

180 185 190

Leu Ser Leu Asp Leu Ala Leu Ser Lys Tyr Leu Ser Asp Leu Leu Phe

195 200 205

Val Phe Gly Pro Asn Leu Gln Asp Pro Val Ser Asn Ser Met Thr Ile

210 215 220

Gln Ala Ile Ser Gln Ala Phe Gly Gly Asn Tyr Glu Thr Leu Leu Arg

225 230 235 240

Thr Leu Gly Tyr Ala Thr Glu Asp Phe Asp Asp Leu Leu Glu Ser Asp

245 250 255

Ser Ile Thr Gly Gln Ile Ile Tyr Val Asp Leu Ser Ser Tyr Tyr Ile

260 265 270

Ile Val Arg Val Tyr Phe Pro Ile Leu Thr Glu Ile Gln Gln Ala Tyr

275 280 285

Ile Gln Glu Leu Leu Pro Val Ser Phe Asn Asn Asp Asn Ser Glu Trp

290 295 300

Ile Ser Ile Val Pro Asn Phe Ile Leu Val Arg Asn Thr Leu Ile Ser

305 310 315 320

Asn Ile Glu Ile Gly Phe Cys Leu Ile Thr Lys Arg Ser Val Ile Cys

325 330 335

Asn Gln Asp Tyr Ala Thr Pro Met Thr Asn Asn Met Arg Glu Cys Leu

340 345 350

Thr Gly Ser Thr Glu Lys Cys Pro Arg Glu Leu Val Val Ser Ser His

355 360 365

Val Pro Arg Phe Ala Leu Ser Asn Gly Val Leu Phe Ala Asn Cys Ile

370 375 380

Ser Val Thr Cys Gln Cys Gln Thr Thr Gly Arg Ala Ile Ser Gln Ser

385 390 395 400

Gly Glu Gln Thr Leu Leu Met Ile Asp Asn Thr Thr Cys Pro Thr Ala

405 410 415

Val Leu Gly Asn Val Ile Ile Ser Leu Gly Lys Tyr Leu Gly Ser Val

420 425 430

Asn Tyr Asn Ser Glu Gly Ile Ala Ile Gly Pro Pro Val Phe Thr Asp

435 440 445

Lys Val Asp Ile Ser Ser Gln Ile Ser Ser Met Asn Gln Ser Leu Gln

450 455 460

Gln Ser Lys Asp Tyr Ile Lys Glu Ala Gln Arg Leu Leu Asp Thr Val

465 470 475 480

Asn Pro Ser Leu Lys Leu Met Lys Gln Ile Glu Asp Lys Ile Glu Glu

485 490 495

Ile Leu Ser Lys Ile Tyr His Ile Glu Asn Glu Ile Ala Arg Ile Lys

500 505 510

Lys Leu Ile Gly Glu Ala Pro Gly Gly Leu Val Pro Arg Gly Ser His

515 520 525

His His His His His Ser Ala Trp Ser His Pro Gln Phe Glu Lys

530 535 540

<210> 6

<211> 529

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 6

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Gly Ile Leu His Tyr Glu Lys Leu Ser Lys Ile

20 25 30

Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro

35 40 45

Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn Val Ser Asn Met

50 55 60

Ser Gln Cys Thr Gly Ser Val Met Glu Asn Tyr Lys Thr Arg Leu Asn

65 70 75 80

Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile Tyr Lys Asn Gly

85 90 95

Gly Ser Gly Val Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile Thr Ala

100 105 110

Gly Val Ala Leu Tyr Glu Ala Met Lys Asn Ala Asp Asn Ile Asn Lys

115 120 125

Leu Lys Ser Ser Ile Glu Ser Thr Asn Glu Ala Val Val Lys Leu Gln

130 135 140

Glu Thr Ala Glu Lys Thr Val Tyr Val Leu Thr Ala Leu Gln Asp Tyr

145 150 155 160

Ile Asn Thr Asn Leu Val Pro Thr Ile Asp Lys Ile Ser Cys Lys Gln

165 170 175

Thr Glu Leu Ser Leu Asp Leu Ala Leu Ser Lys Tyr Leu Ser Asp Leu

180 185 190

Leu Phe Val Phe Gly Pro Asn Leu Gln Asp Pro Val Ser Asn Ser Met

195 200 205

Thr Ile Gln Ala Ile Ser Gln Ala Phe Gly Gly Asn Tyr Glu Thr Leu

210 215 220

Leu Arg Thr Leu Gly Tyr Ala Thr Glu Asp Phe Asp Asp Leu Leu Glu

225 230 235 240

Ser Asp Ser Ile Thr Gly Gln Ile Ile Tyr Val Asp Leu Ser Ser Tyr

245 250 255

Tyr Ile Ile Val Arg Val Tyr Phe Pro Ile Leu Thr Glu Ile Gln Gln

260 265 270

Ala Tyr Ile Gln Glu Leu Leu Pro Val Ser Phe Asn Asn Asp Asn Ser

275 280 285

Glu Trp Ile Ser Ile Val Pro Asn Phe Ile Leu Val Arg Asn Thr Leu

290 295 300

Ile Ser Asn Ile Glu Ile Gly Phe Cys Leu Ile Thr Lys Arg Ser Val

305 310 315 320

Ile Cys Asn Gln Asp Tyr Ala Thr Pro Met Thr Asn Asn Met Arg Glu

325 330 335

Cys Leu Thr Gly Ser Thr Glu Lys Cys Pro Arg Glu Leu Val Val Ser

340 345 350

Ser His Val Pro Arg Phe Ala Leu Ser Asn Gly Val Leu Phe Ala Asn

355 360 365

Cys Ile Ser Val Thr Cys Gln Cys Gln Thr Thr Gly Arg Ala Ile Ser

370 375 380

Gln Ser Gly Glu Gln Thr Leu Leu Met Ile Asp Asn Thr Thr Cys Pro

385 390 395 400

Thr Ala Val Leu Gly Asn Val Ile Ile Ser Leu Gly Lys Tyr Leu Gly

405 410 415

Ser Val Asn Tyr Asn Ser Glu Gly Ile Ala Ile Gly Pro Pro Val Phe

420 425 430

Thr Asp Lys Val Asp Ile Ser Ser Gln Ile Ser Ser Met Asn Gln Ser

435 440 445

Leu Gln Gln Ser Lys Asp Tyr Ile Lys Glu Ala Gln Arg Leu Leu Asp

450 455 460

Thr Val Asn Pro Ser Leu Lys Leu Met Lys Gln Ile Glu Asp Lys Ile

465 470 475 480

Glu Glu Ile Leu Ser Lys Ile Tyr His Ile Glu Asn Glu Ile Ala Arg

485 490 495

Ile Lys Lys Leu Ile Gly Glu Ala Pro Gly Gly Leu Val Pro Arg Gly

500 505 510

Ser His His His His His His Ser Ala Trp Ser His Pro Gln Phe Glu

515 520 525

Lys

<210> 7

<211> 543

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 7

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Gly Ile Leu His Tyr Glu Lys Leu Ser Lys Ile

20 25 30

Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro

35 40 45

Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn Val Ser Asn Met

50 55 60

Ser Gln Cys Thr Gly Ser Val Met Glu Asn Tyr Lys Thr Arg Leu Asn

65 70 75 80

Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile Tyr Lys Asn Asn

85 90 95

Thr His Asp Leu Val Gly Asp Val Arg Leu Ala Gly Val Cys Met Ala

100 105 110

Gly Val Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile Thr Ala Gly Val

115 120 125

Ala Leu Tyr Glu Ala Met Lys Asn Ala Asp Asn Ile Asn Lys Leu Lys

130 135 140

Ser Ser Ile Glu Ser Thr Asn Glu Ala Val Val Lys Leu Gln Glu Thr

145 150 155 160

Ala Glu Lys Thr Val Tyr Val Leu Thr Ala Leu Gln Asp Tyr Ile Asn

165 170 175

Thr Asn Leu Val Pro Thr Ile Asp Lys Ile Ser Cys Lys Gln Thr Glu

180 185 190

Leu Ser Leu Asp Leu Ala Leu Ser Lys Tyr Leu Ser Asp Leu Leu Phe

195 200 205

Val Phe Gly Pro Asn Leu Gln Asp Pro Val Ser Asn Ser Met Thr Ile

210 215 220

Gln Ala Ile Ser Gln Ala Phe Gly Gly Asn Tyr Glu Thr Leu Leu Arg

225 230 235 240

Thr Leu Gly Tyr Ala Thr Glu Asp Phe Asp Asp Leu Leu Glu Ser Asp

245 250 255

Ser Ile Thr Gly Gln Ile Ile Tyr Val Asp Leu Ser Ser Tyr Tyr Ile

260 265 270

Ile Val Arg Val Tyr Phe Pro Ile Leu Thr Glu Ile Gln Gln Ala Tyr

275 280 285

Ile Gln Glu Leu Leu Pro Val Ser Phe Asn Asn Asp Asn Ser Glu Trp

290 295 300

Ile Ser Ile Val Pro Asn Phe Ile Leu Val Arg Asn Thr Leu Ile Ser

305 310 315 320

Asn Ile Glu Ile Gly Phe Cys Leu Ile Thr Lys Arg Ser Val Ile Cys

325 330 335

Asn Gln Asp Tyr Ala Thr Pro Met Thr Asn Asn Met Arg Glu Cys Leu

340 345 350

Thr Gly Ser Thr Glu Lys Cys Pro Arg Glu Leu Val Val Ser Ser His

355 360 365

Val Pro Arg Phe Ala Leu Ser Asn Gly Val Leu Phe Ala Asn Cys Ile

370 375 380

Ser Val Thr Cys Gln Cys Gln Thr Thr Gly Arg Ala Ile Ser Gln Ser

385 390 395 400

Gly Glu Gln Thr Leu Leu Met Ile Asp Asn Thr Thr Cys Pro Thr Ala

405 410 415

Val Leu Gly Asn Val Cys Ile Ser Leu Gly Lys Tyr Leu Gly Ser Val

420 425 430

Asn Tyr Asn Ser Glu Gly Ile Ala Ile Gly Pro Pro Val Phe Thr Asp

435 440 445

Lys Val Asp Ile Ser Ser Gln Ile Ser Ser Met Asn Gln Ser Leu Gln

450 455 460

Gln Ser Lys Asp Tyr Ile Lys Glu Ala Gln Arg Leu Leu Asp Thr Val

465 470 475 480

Asn Pro Ser Leu Lys Leu Met Lys Gln Ile Glu Asp Lys Ile Glu Glu

485 490 495

Ile Leu Ser Lys Ile Tyr His Ile Glu Asn Glu Ile Ala Arg Ile Lys

500 505 510

Lys Leu Ile Gly Glu Ala Pro Gly Gly Leu Val Pro Arg Gly Ser His

515 520 525

His His His His His Ser Ala Trp Ser His Pro Gln Phe Glu Lys

530 535 540

<210> 8

<211> 543

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 8

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Gly Ile Leu His Tyr Glu Lys Leu Ser Lys Ile

20 25 30

Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro

35 40 45

Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn Val Ser Asp Met

50 55 60

Ser Gln Cys Thr Gly Ser Val Met Glu Asn Tyr Lys Thr Arg Leu Asn

65 70 75 80

Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile Tyr Lys Asn Asn

85 90 95

Thr His Asp Leu Val Gly Asp Val Arg Leu Ala Gly Val Ile Met Ala

100 105 110

Gly Val Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile Thr Ala Gly Val

115 120 125

Ala Leu Tyr Glu Ala Met Lys Asn Ala Asp Asn Ile Asn Lys Leu Lys

130 135 140

Ser Ser Ile Glu Ser Thr Asn Glu Ala Val Val Lys Leu Gln Glu Thr

145 150 155 160

Ala Glu Lys Thr Val Tyr Val Phe Thr Ala Leu Gln Asp Tyr Ile Asn

165 170 175

Thr Asn Leu Val Pro Thr Ile Asp Lys Ile Ser Cys Lys Gln Thr Glu

180 185 190

Leu Ser Leu Asp Leu Ala Leu Ser Lys Tyr Leu Ser Asp Leu Leu Phe

195 200 205

Val Phe Gly Pro Asn Leu Gln Asp Pro Val Ser Asn Ser Met Thr Ile

210 215 220

Gln Ala Ile Ser Gln Ala Phe Gly Gly Asn Tyr Glu Thr Leu Leu Arg

225 230 235 240

Thr Leu Gly Tyr Ala Thr Glu Asp Phe Asp Asp Leu Leu Glu Ser Asp

245 250 255

Ser Ile Thr Gly Gln Ile Ile Tyr Val Asp Leu Ser Ser Tyr Tyr Ile

260 265 270

Ile Val Arg Val Tyr Phe Pro Ile Leu Thr Glu Ile Gln Gln Ala Tyr

275 280 285

Ile Gln Glu Leu Leu Pro Val Ser Phe Asn Asn Asp Asp Ser Glu Trp

290 295 300

Ile Ser Ile Val Pro Asn Phe Ile Leu Val Arg Asn Thr Leu Ile Ser

305 310 315 320

Asn Ile Glu Ile Gly Phe Cys Leu Ile Thr Lys Arg Ser Val Ile Cys

325 330 335

Asn Gln Asp Tyr Ala Thr Pro Met Thr Asn Asn Met Arg Glu Cys Leu

340 345 350

Thr Gly Ser Thr Glu Lys Cys Pro Arg Glu Leu Val Val Ser Ser His

355 360 365

Val Pro Arg Phe Ala Leu Ser Asn Gly Val Leu Phe Ala Asn Cys Ile

370 375 380

Ser Val Thr Cys Gln Cys Gln Thr Thr Gly Arg Ala Ile Ser Gln Ser

385 390 395 400

Gly Glu Gln Thr Leu Leu Met Ile Asp Asn Thr Thr Cys Pro Thr Ala

405 410 415

Val Leu Gly Asn Val Ile Ile Ser Leu Gly Lys Tyr Leu Gly Ser Val

420 425 430

Asn Tyr Asn Ser Glu Gly Ile Ala Ile Gly Pro Pro Val Phe Thr Asp

435 440 445

Lys Val Asp Ile Ser Ser Gln Ile Ser Ser Met Asn Gln Ser Leu Gln

450 455 460

Gln Ser Lys Asp Tyr Ile Lys Glu Ala Gln Arg Leu Leu Asp Thr Val

465 470 475 480

Asn Pro Ser Leu Lys Leu Met Lys Gln Ile Glu Asp Lys Ile Glu Glu

485 490 495

Ile Leu Ser Lys Ile Tyr His Ile Glu Asn Glu Ile Ala Arg Ile Lys

500 505 510

Lys Leu Ile Gly Glu Ala Pro Gly Gly Leu Val Pro Arg Gly Ser His

515 520 525

His His His His His Ser Ala Trp Ser His Pro Gln Phe Glu Lys

530 535 540

<210> 9

<211> 543

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 9

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Gly Ile Leu His Tyr Glu Lys Leu Ser Lys Ile

20 25 30

Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro

35 40 45

Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn Val Ser Asn Met

50 55 60

Ser Gln Cys Thr Gly Ser Val Met Glu Asn Tyr Lys Thr Arg Leu Asn

65 70 75 80

Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile Tyr Lys Asn Asn

85 90 95

Thr His Asp Leu Val Gly Asp Val Arg Leu Ala Gly Val Ile Met Ala

100 105 110

Gly Val Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile Thr Ala Gly Val

115 120 125

Ala Leu Tyr Glu Ala Met Lys Asn Ala Asp Asn Ile Asn Lys Leu Lys

130 135 140

Ser Ser Ile Glu Ser Thr Asn Glu Ala Val Val Lys Leu Gln Glu Thr

145 150 155 160

Ala Glu Lys Thr Val Tyr Val Leu Thr Ala Leu Gln Asp Tyr Ile Asn

165 170 175

Thr Asn Leu Val Pro Thr Ile Asp Lys Ile Pro Cys Lys Gln Thr Glu

180 185 190

Leu Ser Leu Asp Leu Ala Leu Ser Lys Tyr Leu Ser Asp Leu Leu Phe

195 200 205

Val Phe Gly Pro Asn Leu Gln Asp Pro Val Ser Asn Ser Met Thr Ile

210 215 220

Gln Ala Ile Ser Gln Ala Phe Gly Gly Asn Tyr Glu Thr Leu Leu Arg

225 230 235 240

Thr Leu Gly Tyr Ala Thr Glu Asp Phe Asp Asp Leu Leu Glu Ser Asp

245 250 255

Ser Ile Thr Gly Gln Ile Ile Tyr Val Asp Leu Ser Ser Tyr Tyr Ile

260 265 270

Ile Val Arg Val Tyr Phe Pro Ile Leu Thr Glu Ile Gln Gln Ala Tyr

275 280 285

Ile Gln Glu Leu Leu Pro Val Ser Phe Asn Asn Asp Asn Ser Glu Trp

290 295 300

Ile Ser Ile Val Pro Asn Phe Ile Leu Val Arg Asn Thr Leu Ile Ser

305 310 315 320

Asn Ile Glu Ile Gly Phe Cys Leu Ile Thr Lys Arg Ser Val Ile Cys

325 330 335

Asn Gln Asp Tyr Ala Thr Pro Met Thr Asn Asn Met Arg Glu Cys Leu

340 345 350

Thr Gly Ser Thr Glu Lys Cys Pro Arg Glu Leu Val Val Ser Ser His

355 360 365

Val Pro Arg Phe Ala Leu Ser Asn Gly Val Leu Phe Ala Asn Cys Ile

370 375 380

Ser Val Thr Cys Gln Cys Gln Thr Thr Gly Arg Ala Ile Ser Gln Ser

385 390 395 400

Gly Glu Gln Thr Leu Leu Met Ile Asp Asn Thr Thr Cys Pro Thr Ala

405 410 415

Val Leu Gly Asn Val Ile Ile Ser Leu Gly Lys Tyr Leu Gly Ser Val

420 425 430

Asn Tyr Asn Ser Glu Gly Ile Ala Ile Gly Pro Pro Val Phe Thr Asp

435 440 445

Lys Val Asp Ile Ser Ser Gln Ile Ser Ser Met Asn Gln Ser Leu Gln

450 455 460

Gln Ser Lys Asp Tyr Ile Lys Glu Ala Gln Arg Leu Leu Asp Thr Val

465 470 475 480

Asn Pro Ser Leu Lys Leu Met Lys Gln Ile Glu Asp Lys Ile Glu Glu

485 490 495

Ile Leu Ser Lys Ile Tyr His Ile Glu Asn Glu Ile Ala Arg Ile Lys

500 505 510

Lys Leu Ile Gly Glu Ala Pro Gly Gly Leu Val Pro Arg Gly Ser His

515 520 525

His His His His His Ser Ala Trp Ser His Pro Gln Phe Glu Lys

530 535 540

<210> 10

<211> 526

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 10

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Gly Ile Leu His Tyr Glu Lys Leu Ser Lys Ile

20 25 30

Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro

35 40 45

Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn Val Ser Asn Met

50 55 60

Ser Gln Cys Thr Gly Ser Val Met Glu Asn Tyr Lys Thr Arg Leu Asn

65 70 75 80

Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile Tyr Lys Asn Gly

85 90 95

Val Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile Thr Ala Gly Val Ala

100 105 110

Leu Tyr Glu Ala Met Lys Asn Ala Asp Asn Ile Asn Lys Leu Lys Ser

115 120 125

Ser Ile Glu Ser Thr Asn Glu Ala Val Val Lys Leu Gln Glu Thr Ala

130 135 140

Glu Lys Thr Val Tyr Val Leu Thr Ala Leu Gln Asp Tyr Ile Asn Thr

145 150 155 160

Asn Leu Val Pro Thr Ile Asp Lys Ile Ser Cys Lys Gln Thr Glu Leu

165 170 175

Ser Leu Asp Leu Ala Leu Ser Lys Tyr Leu Ser Asp Leu Leu Phe Val

180 185 190

Phe Gly Pro Asn Leu Gln Asp Pro Val Ser Asn Ser Met Thr Ile Gln

195 200 205

Ala Ile Ser Gln Ala Phe Gly Gly Asn Tyr Glu Thr Leu Leu Arg Thr

210 215 220

Leu Gly Tyr Ala Thr Glu Asp Phe Asp Asp Leu Leu Glu Ser Asp Ser

225 230 235 240

Ile Thr Gly Gln Ile Ile Tyr Val Asp Leu Ser Ser Tyr Tyr Ile Ile

245 250 255

Val Arg Val Tyr Phe Pro Ile Leu Thr Glu Ile Gln Gln Ala Tyr Ile

260 265 270

Gln Glu Leu Leu Pro Val Ser Phe Asn Asn Asp Asn Ser Glu Trp Ile

275 280 285

Ser Ile Val Pro Asn Phe Ile Leu Val Arg Asn Thr Leu Ile Ser Asn

290 295 300

Ile Glu Ile Gly Phe Cys Leu Ile Thr Lys Arg Ser Val Ile Cys Asn

305 310 315 320

Gln Asp Tyr Ala Thr Pro Met Thr Asn Asn Met Arg Glu Cys Leu Thr

325 330 335

Gly Ser Thr Glu Lys Cys Pro Arg Glu Leu Val Val Ser Ser His Val

340 345 350

Pro Arg Phe Ala Leu Ser Asn Gly Val Leu Phe Ala Asn Cys Ile Ser

355 360 365

Val Thr Cys Gln Cys Gln Thr Thr Gly Arg Ala Ile Ser Gln Ser Gly

370 375 380

Glu Gln Thr Leu Leu Met Ile Asp Asn Thr Thr Cys Pro Thr Ala Val

385 390 395 400

Leu Gly Asn Val Ile Ile Ser Leu Gly Lys Tyr Leu Gly Ser Val Asn

405 410 415

Tyr Asn Ser Glu Gly Ile Ala Ile Gly Pro Pro Val Phe Thr Asp Lys

420 425 430

Val Asp Ile Ser Ser Gln Ile Ser Ser Met Asn Gln Ser Leu Gln Gln

435 440 445

Ser Lys Asp Tyr Ile Lys Glu Ala Gln Arg Leu Leu Asp Thr Val Asn

450 455 460

Pro Ser Leu Lys Leu Met Lys Gln Ile Glu Asp Lys Ile Glu Glu Ile

465 470 475 480

Leu Ser Lys Ile Tyr His Ile Glu Asn Glu Ile Ala Arg Ile Lys Lys

485 490 495

Leu Ile Gly Glu Ala Pro Gly Gly Leu Val Pro Arg Gly Ser His His

500 505 510

His His His His Ser Ala Trp Ser His Pro Gln Phe Glu Lys

515 520 525

<210> 11

<211> 543

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 11

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Gly Ile Leu His Tyr Glu Lys Leu Ser Lys Ile

20 25 30

Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro

35 40 45

Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn Val Ser Asn Met

50 55 60

Ser Gln Cys Thr Gly Ser Val Met Glu Asn Tyr Lys Thr Arg Leu Asn

65 70 75 80

Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile Tyr Lys Asn Asn

85 90 95

Thr His Asp Leu Val Gly Asp Val Arg Leu Ala Gly Val Ile Met Ala

100 105 110

Gly Val Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile Thr Ala Gly Val

115 120 125

Ala Leu Tyr Glu Ala Met Lys Asn Ala Asp Asn Ile Asn Lys Leu Lys

130 135 140

Ser Ser Ile Glu Ser Thr Asn Glu Ala Val Val Lys Leu Gln Glu Thr

145 150 155 160

Ala Glu Lys Thr Val Tyr Val Leu Thr Ala Leu Gln Asp Trp Ile Asn

165 170 175

Thr Asn Leu Val Pro Thr Ile Asp Lys Ile Ser Cys Lys Gln Thr Glu

180 185 190

Leu Ser Leu Asp Leu Ala Leu Ser Lys Tyr Leu Ser Asp Leu Leu Phe

195 200 205

Val Phe Gly Pro Asn Leu Gln Asp Pro Val Ser Asn Ser Met Thr Ile

210 215 220

Gln Ala Ile Ser Gln Ala Phe Gly Gly Asn Tyr Glu Thr Leu Leu Arg

225 230 235 240

Thr Leu Gly Tyr Ala Thr Glu Asp Phe Asp Asp Leu Leu Glu Ser Asp

245 250 255

Ser Ile Thr Gly Gln Ile Ile Tyr Val Asp Leu Ser Ser Tyr Tyr Ile

260 265 270

Ile Val Arg Val Tyr Phe Pro Ile Leu Thr Glu Ile Gln Gln Ala Tyr

275 280 285

Ile Gln Glu Leu Leu Pro Val Ser Phe Asn Asn Asp Asn Ser Glu Trp

290 295 300

Ile Ser Ile Val Pro Asn Phe Ile Leu Val Arg Asn Thr Leu Ile Ser

305 310 315 320

Asn Ile Glu Ile Gly Phe Cys Leu Ile Thr Lys Arg Ser Val Ile Cys

325 330 335

Asn Gln Asp Tyr Ala Thr Pro Met Thr Asn Asn Met Arg Glu Cys Leu

340 345 350

Thr Gly Ser Thr Glu Lys Cys Pro Arg Glu Leu Val Val Ser Ser His

355 360 365

Val Pro Arg Phe Ala Leu Ser Asn Gly Val Leu Phe Ala Asn Cys Ile

370 375 380

Ser Val Thr Cys Gln Cys Gln Thr Thr Gly Arg Ala Ile Ser Gln Ser

385 390 395 400

Gly Glu Gln Thr Leu Leu Met Ile Asp Asn Thr Thr Cys Pro Thr Ala

405 410 415

Val Leu Gly Asn Val Ile Ile Ser Leu Gly Lys Tyr Leu Gly Ser Val

420 425 430

Asn Tyr Asn Ser Glu Gly Ile Ala Ile Gly Pro Pro Val Phe Thr Asp

435 440 445

Lys Val Asp Ile Ser Ser Gln Ile Ser Ser Met Asn Gln Ser Leu Gln

450 455 460

Gln Ser Lys Asp Tyr Ile Lys Glu Ala Gln Arg Leu Leu Asp Thr Val

465 470 475 480

Asn Pro Ser Leu Lys Leu Met Lys Gln Ile Glu Asp Lys Ile Glu Glu

485 490 495

Ile Leu Ser Lys Ile Tyr His Ile Glu Asn Glu Ile Ala Arg Ile Lys

500 505 510

Lys Leu Ile Gly Glu Ala Pro Gly Gly Leu Val Pro Arg Gly Ser His

515 520 525

His His His His His Ser Ala Trp Ser His Pro Gln Phe Glu Lys

530 535 540

<210> 12

<211> 543

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 12

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Gly Ile Leu His Tyr Glu Lys Leu Ser Lys Ile

20 25 30

Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro

35 40 45

Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn Val Ser Asn Met

50 55 60

Ser Gln Cys Thr Gly Ser Val Met Glu Asn Tyr Lys Thr Arg Leu Asn

65 70 75 80

Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile Tyr Lys Asn Asn

85 90 95

Thr His Asp Leu Val Gly Asp Val Arg Leu Ala Gly Val Ile Met Ala

100 105 110

Gly Val Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile Thr Cys Gly Val

115 120 125

Ala Leu Tyr Glu Ala Met Lys Asn Ala Asp Asn Ile Asn Lys Leu Lys

130 135 140

Ser Ser Ile Glu Ser Thr Asn Glu Ala Val Val Lys Leu Gln Glu Thr

145 150 155 160

Ala Glu Lys Thr Val Tyr Val Leu Thr Ala Leu Gln Asp Tyr Ile Asn

165 170 175

Thr Asn Leu Val Pro Thr Ile Asp Lys Ile Ser Cys Lys Gln Thr Glu

180 185 190

Leu Ser Leu Asp Leu Ala Leu Ser Lys Tyr Leu Ser Asp Leu Leu Phe

195 200 205

Val Phe Gly Pro Asn Leu Gln Asp Pro Cys Ser Asn Ser Met Thr Ile

210 215 220

Gln Ala Ile Ser Gln Ala Phe Gly Gly Asn Tyr Glu Thr Leu Leu Arg

225 230 235 240

Thr Leu Gly Tyr Ala Thr Glu Asp Phe Asp Asp Leu Leu Glu Ser Asp

245 250 255

Ser Ile Thr Gly Gln Ile Ile Tyr Val Asp Leu Ser Ser Tyr Tyr Ile

260 265 270

Ile Val Arg Val Tyr Phe Pro Ile Leu Thr Glu Ile Gln Gln Ala Tyr

275 280 285

Ile Gln Glu Leu Leu Pro Val Ser Phe Asn Asn Asp Asn Ser Glu Trp

290 295 300

Ile Ser Ile Val Pro Asn Phe Ile Leu Val Arg Asn Thr Leu Ile Ser

305 310 315 320

Asn Ile Glu Ile Gly Phe Cys Leu Ile Thr Lys Arg Ser Val Ile Cys

325 330 335

Asn Gln Asp Tyr Ala Thr Pro Met Thr Asn Asn Met Arg Glu Cys Leu

340 345 350

Thr Gly Ser Thr Glu Lys Cys Pro Arg Glu Leu Val Val Ser Ser His

355 360 365

Val Pro Arg Phe Ala Leu Ser Asn Gly Val Leu Phe Ala Asn Cys Ile

370 375 380

Ser Val Thr Cys Gln Cys Gln Thr Thr Gly Arg Ala Ile Ser Gln Ser

385 390 395 400

Gly Glu Gln Thr Leu Leu Met Ile Asp Asn Thr Thr Cys Pro Thr Ala

405 410 415

Val Leu Gly Asn Val Ile Ile Ser Leu Gly Lys Tyr Leu Gly Ser Val

420 425 430

Asn Tyr Asn Ser Glu Gly Ile Ala Ile Gly Pro Pro Val Phe Thr Asp

435 440 445

Lys Val Asp Ile Ser Ser Gln Ile Ser Ser Met Asn Gln Ser Leu Gln

450 455 460

Gln Ser Lys Asp Tyr Ile Lys Glu Ala Gln Arg Leu Leu Asp Thr Val

465 470 475 480

Asn Pro Ser Leu Lys Leu Met Lys Gln Ile Glu Asp Lys Ile Glu Glu

485 490 495

Ile Leu Ser Lys Ile Tyr His Ile Glu Asn Glu Ile Ala Arg Ile Lys

500 505 510

Lys Leu Ile Gly Glu Ala Pro Gly Gly Leu Val Pro Arg Gly Ser His

515 520 525

His His His His His Ser Ala Trp Ser His Pro Gln Phe Glu Lys

530 535 540

<210> 13

<211> 543

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 13

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Gly Ile Leu His Tyr Glu Lys Leu Ser Lys Ile

20 25 30

Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro

35 40 45

Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn Val Ser Asn Met

50 55 60

Ser Gly Cys Thr Gly Ser Val Met Glu Asn Tyr Lys Thr Arg Leu Asn

65 70 75 80

Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile Tyr Lys Asn Asn

85 90 95

Thr His Asp Leu Val Gly Asp Val Arg Leu Ala Gly Val Ile Met Ala

100 105 110

Gly Val Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile Thr Ala Gly Val

115 120 125

Ala Leu Tyr Glu Ala Met Lys Asn Ala Asp Asn Ile Asn Lys Leu Lys

130 135 140

Ser Ser Ile Glu Ser Thr Asn Glu Ala Val Val Lys Leu Gln Glu Thr

145 150 155 160

Ala Glu Lys Thr Val Tyr Val Leu Thr Ala Leu Gln Asp Tyr Ile Asn

165 170 175

Thr Asn Leu Val Pro Thr Ile Asp Lys Ile Ser Cys Lys Gln Thr Glu

180 185 190

Leu Ser Leu Asp Leu Ala Leu Ser Lys Tyr Leu Ser Asp Leu Leu Phe

195 200 205

Val Phe Gly Pro Asn Leu Gln Asp Pro Val Ser Asn Ser Met Thr Ile

210 215 220

Gln Ala Ile Ser Gln Ala Phe Gly Gly Asn Tyr Glu Thr Leu Leu Arg

225 230 235 240

Thr Leu Gly Tyr Ala Thr Glu Asp Phe Asp Asp Leu Leu Glu Ser Asp

245 250 255

Ser Ile Thr Gly Gln Ile Ile Tyr Val Asp Leu Ser Ser Tyr Tyr Ile

260 265 270

Ile Val Arg Val Tyr Phe Pro Ile Leu Thr Glu Ile Gln Gln Ala Tyr

275 280 285

Ile Gln Glu Leu Leu Pro Val Ser Phe Asn Asn Asp Asn Ser Glu Trp

290 295 300

Ile Ser Ile Val Pro Asn Phe Ile Leu Val Arg Asn Thr Leu Ile Ser

305 310 315 320

Asn Ile Glu Ile Gly Phe Cys Leu Ile Thr Lys Arg Ser Val Ile Cys

325 330 335

Asn Gln Asp Tyr Ala Thr Pro Met Thr Asn Asn Met Arg Glu Cys Leu

340 345 350

Thr Gly Ser Thr Glu Lys Cys Pro Arg Glu Leu Val Val Ser Ser His

355 360 365

Val Pro Arg Phe Ala Leu Ser Asn Gly Val Leu Phe Ala Asn Cys Ile

370 375 380

Ser Val Thr Cys Gln Cys Gln Thr Thr Gly Arg Ala Ile Ser Gln Ser

385 390 395 400

Gly Glu Gln Thr Leu Leu Met Ile Asp Asn Thr Thr Cys Pro Thr Ala

405 410 415

Val Leu Gly Asn Val Ile Ile Ser Leu Gly Lys Tyr Leu Gly Ser Val

420 425 430

Asn Tyr Asn Ser Glu Gly Ile Ala Ile Gly Pro Pro Val Phe Thr Asp

435 440 445

Lys Val Asp Ile Ser Ser Gln Ile Ser Ser Met Asn Gln Ser Leu Gln

450 455 460

Gln Ser Lys Asp Tyr Ile Lys Glu Ala Gln Arg Leu Leu Asp Thr Val

465 470 475 480

Asn Pro Ser Leu Lys Leu Met Lys Gln Ile Glu Asp Lys Ile Glu Glu

485 490 495

Ile Leu Ser Lys Ile Tyr His Ile Glu Asn Glu Ile Ala Arg Ile Lys

500 505 510

Lys Leu Ile Gly Glu Ala Pro Gly Gly Leu Val Pro Arg Gly Ser His

515 520 525

His His His His His Ser Ala Trp Ser His Pro Gln Phe Glu Lys

530 535 540

<210> 14

<211> 543

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 14

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Gly Ile Leu His Tyr Glu Lys Leu Ser Lys Ile

20 25 30

Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro

35 40 45

Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn Val Ser Asn Met

50 55 60

Ser Gln Cys Thr Gly Ser Val Met Glu Asn Tyr Lys Thr Arg Leu Asn

65 70 75 80

Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile Tyr Lys Asn Asn

85 90 95

Thr His Asp Leu Val Gly Asp Val Arg Leu Ala Gly Val Ile Met Ala

100 105 110

Gly Val Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile Thr Ala Gly Val

115 120 125

Ala Leu Tyr Glu Ala Met Lys Asn Ala Asp Asn Ile Asn Lys Leu Lys

130 135 140

Ser Ser Ile Glu Ser Thr Asn Glu Ala Val Val Lys Leu Gln Glu Thr

145 150 155 160

Ala Glu Lys Thr Val Tyr Val Leu Thr Ala Leu Gln Asp Tyr Ile Asn

165 170 175

Thr Asn Leu Val Pro Thr Ile Gly Lys Ile Gly Cys Lys Gln Thr Glu

180 185 190

Leu Ser Leu Asp Leu Ala Leu Ser Lys Tyr Leu Ser Asp Leu Leu Phe

195 200 205

Val Phe Gly Pro Asn Leu Gln Asp Pro Val Ser Asn Ser Met Thr Ile

210 215 220

Gln Ala Ile Ser Gln Ala Phe Gly Gly Asn Tyr Glu Thr Leu Leu Arg

225 230 235 240

Thr Leu Gly Tyr Ala Thr Glu Asp Phe Asp Asp Leu Leu Glu Ser Asp

245 250 255

Ser Ile Thr Gly Gln Ile Ile Tyr Val Asp Leu Ser Ser Tyr Tyr Ile

260 265 270

Ile Val Arg Val Tyr Phe Pro Ile Leu Thr Glu Ile Gln Gln Ala Tyr

275 280 285

Ile Gln Glu Leu Leu Pro Val Ser Phe Asn Asn Asp Asn Ser Glu Trp

290 295 300

Ile Ser Ile Val Pro Asn Phe Ile Leu Val Arg Asn Thr Leu Ile Ser

305 310 315 320

Asn Ile Glu Ile Gly Phe Cys Leu Ile Thr Lys Arg Ser Val Ile Cys

325 330 335

Asn Gln Asp Tyr Ala Thr Pro Met Thr Asn Asn Met Arg Glu Cys Leu

340 345 350

Thr Gly Ser Thr Glu Lys Cys Pro Arg Glu Leu Val Val Ser Ser His

355 360 365

Val Pro Arg Phe Ala Leu Ser Asn Gly Val Leu Phe Ala Asn Cys Ile

370 375 380

Ser Val Thr Cys Gln Cys Gln Thr Thr Gly Arg Ala Ile Ser Gln Ser

385 390 395 400

Gly Glu Gln Thr Leu Leu Met Ile Asp Asn Thr Thr Cys Pro Thr Ala

405 410 415

Val Leu Gly Asn Val Ile Ile Ser Leu Gly Lys Tyr Leu Gly Ser Val

420 425 430

Asn Tyr Asn Ser Glu Gly Ile Ala Ile Gly Pro Pro Val Phe Thr Asp

435 440 445

Lys Val Asp Ile Ser Ser Gln Ile Ser Ser Met Asn Gln Ser Leu Gln

450 455 460

Gln Ser Lys Asp Tyr Ile Lys Glu Ala Gln Arg Leu Leu Asp Thr Val

465 470 475 480

Asn Pro Ser Leu Lys Leu Met Lys Gln Ile Glu Asp Lys Ile Glu Glu

485 490 495

Ile Leu Ser Lys Ile Tyr His Ile Glu Asn Glu Ile Ala Arg Ile Lys

500 505 510

Lys Leu Ile Gly Glu Ala Pro Gly Gly Leu Val Pro Arg Gly Ser His

515 520 525

His His His His His Ser Ala Trp Ser His Pro Gln Phe Glu Lys

530 535 540

<210> 15

<211> 543

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 15

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Gly Ile Leu His Tyr Glu Lys Leu Ser Lys Ile

20 25 30

Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro

35 40 45

Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn Val Ser Asp Met

50 55 60

Ser Gln Cys Thr Gly Ser Val Met Glu Asn Tyr Lys Thr Arg Leu Asn

65 70 75 80

Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile Tyr Lys Asn Asn

85 90 95

Thr His Asp Leu Val Gly Asp Val Arg Leu Ala Gly Val Ile Met Ala

100 105 110

Gly Val Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile Thr Ala Gly Val

115 120 125

Ala Leu Tyr Glu Ala Met Lys Asn Ala Asp Asn Ile Asn Lys Leu Lys

130 135 140

Ser Ser Ile Glu Ser Thr Asn Glu Ala Val Val Lys Leu Cys Glu Thr

145 150 155 160

Ala Glu Lys Cys Val Tyr Val Leu Thr Ala Leu Gln Asp Tyr Ile Asn

165 170 175

Thr Asn Leu Val Pro Thr Ile Asp Lys Ile Ser Cys Lys Gln Thr Glu

180 185 190

Leu Ser Leu Asp Leu Ala Leu Ser Lys Tyr Leu Ser Asp Leu Leu Phe

195 200 205

Val Phe Gly Pro Asn Leu Gln Asp Pro Val Ser Asn Ser Met Thr Ile

210 215 220

Gln Ala Ile Ser Gln Ala Phe Gly Gly Asn Tyr Glu Thr Leu Leu Arg

225 230 235 240

Thr Leu Gly Tyr Ala Thr Glu Asp Phe Asp Asp Leu Leu Glu Ser Asp

245 250 255

Ser Ile Thr Gly Gln Ile Ile Tyr Val Asp Leu Ser Ser Tyr Tyr Ile

260 265 270

Ile Val Arg Val Tyr Phe Pro Ile Leu Thr Glu Ile Gln Gln Ala Tyr

275 280 285

Ile Gln Glu Leu Leu Pro Val Ser Phe Asn Asn Asp Asp Ser Glu Trp

290 295 300

Ile Ser Ile Val Pro Asn Phe Ile Leu Val Arg Asn Thr Leu Ile Ser

305 310 315 320

Asn Ile Glu Ile Gly Phe Cys Leu Ile Thr Lys Arg Ser Val Ile Cys

325 330 335

Asn Gln Asp Tyr Ala Thr Pro Met Thr Asn Asn Met Arg Glu Cys Leu

340 345 350

Thr Gly Ser Thr Glu Lys Cys Pro Arg Glu Leu Val Val Ser Ser His

355 360 365

Val Pro Arg Phe Ala Leu Ser Asn Gly Val Leu Phe Ala Asn Cys Ile

370 375 380

Ser Val Thr Cys Gln Cys Gln Thr Thr Gly Arg Ala Ile Ser Gln Ser

385 390 395 400

Gly Glu Gln Thr Leu Leu Met Ile Asp Asn Thr Thr Cys Pro Thr Ala

405 410 415

Val Leu Gly Asn Val Ile Ile Ser Leu Gly Lys Tyr Leu Gly Ser Val

420 425 430

Asn Tyr Asn Ser Glu Gly Ile Ala Ile Gly Pro Pro Val Phe Thr Asp

435 440 445

Lys Val Asp Ile Ser Ser Gln Ile Ser Ser Met Asn Gln Ser Leu Gln

450 455 460

Gln Ser Lys Asp Tyr Ile Lys Glu Ala Gln Arg Leu Leu Asp Thr Val

465 470 475 480

Asn Pro Ser Leu Lys Leu Met Lys Gln Ile Glu Asp Lys Ile Glu Glu

485 490 495

Ile Leu Ser Lys Ile Tyr His Ile Glu Asn Glu Ile Ala Arg Ile Lys

500 505 510

Lys Leu Ile Gly Glu Ala Pro Gly Gly Leu Val Pro Arg Gly Ser His

515 520 525

His His His His His Ser Ala Trp Ser His Pro Gln Phe Glu Lys

530 535 540

<210> 16

<211> 543

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 16

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Gly Ile Leu His Tyr Glu Lys Leu Ser Lys Ile

20 25 30

Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro

35 40 45

Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn Val Ser Asn Met

50 55 60

Ser Gln Cys Thr Gly Ser Val Met Glu Asn Tyr Lys Thr Arg Leu Asn

65 70 75 80

Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile Tyr Lys Asn Asn

85 90 95

Thr His Asp Leu Val Gly Asp Val Arg Leu Ala Gly Val Ile Met Ala

100 105 110

Gly Val Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile Thr Ala Gly Val

115 120 125

Ala Leu Tyr Glu Ala Met Lys Asn Ala Asp Asn Ile Asn Lys Leu Lys

130 135 140

Ser Ser Ile Glu Ser Thr Asn Glu Ala Val Val Lys Leu Gln Glu Thr

145 150 155 160

Ala Glu Lys Thr Val Tyr Val Leu Thr Ala Leu Gln Asp Tyr Ile Asn

165 170 175

Thr Asn Leu Val Pro Thr Ile Asp Lys Ile Ser Cys Lys Gln Thr Glu

180 185 190

Leu Ser Leu Asp Leu Ala Leu Ser Lys Tyr Leu Ser Asp Leu Leu Phe

195 200 205

Val Phe Gly Pro Asn Leu Gln Asp Pro Val Ser Asn Ser Met Thr Phe

210 215 220

Gln Ala Ile Ser Gln Ala Phe Gly Gly Asn Tyr Glu Thr Leu Leu Arg

225 230 235 240

Thr Leu Gly Tyr Ala Thr Glu Asp Phe Asp Asp Leu Leu Glu Ser Asp

245 250 255

Ser Ile Thr Gly Gln Ile Ile Tyr Val Asp Leu Ser Ser Tyr Tyr Ile

260 265 270

Ile Val Arg Val Tyr Phe Pro Ile Leu Thr Glu Ile Gln Gln Ala Tyr

275 280 285

Ile Gln Glu Leu Leu Pro Val Ser Phe Asn Asn Asp Asn Ser Glu Trp

290 295 300

Ile Ser Ile Val Pro Asn Phe Ile Leu Val Arg Asn Thr Leu Ile Ser

305 310 315 320

Asn Ile Glu Ile Gly Phe Cys Leu Ile Thr Lys Arg Ser Val Ile Cys

325 330 335

Asn Gln Asp Tyr Ala Thr Pro Met Thr Asn Asn Met Arg Glu Cys Leu

340 345 350

Thr Gly Ser Thr Glu Lys Cys Pro Arg Glu Leu Val Val Ser Ser His

355 360 365

Val Pro Arg Phe Ala Leu Ser Asn Gly Val Leu Phe Ala Asn Cys Ile

370 375 380

Ser Val Thr Cys Gln Cys Gln Thr Thr Gly Arg Ala Ile Ser Gln Ser

385 390 395 400

Gly Glu Gln Thr Leu Leu Met Ile Asp Asn Thr Thr Cys Pro Thr Ala

405 410 415

Val Leu Gly Asn Val Ile Ile Ser Leu Gly Lys Tyr Leu Gly Ser Val

420 425 430

Asn Tyr Asn Ser Glu Gly Ile Ala Ile Gly Pro Pro Val Phe Thr Asp

435 440 445

Lys Val Asp Ile Ser Ser Gln Ile Ser Ser Met Asn Gln Ser Leu Gln

450 455 460

Gln Ser Lys Asp Tyr Ile Lys Glu Ala Gln Arg Leu Leu Asp Thr Val

465 470 475 480

Asn Pro Ser Leu Lys Leu Met Lys Gln Ile Glu Asp Lys Ile Glu Glu

485 490 495

Ile Leu Ser Lys Ile Tyr His Ile Glu Asn Glu Ile Ala Arg Ile Lys

500 505 510

Lys Leu Ile Gly Glu Ala Pro Gly Gly Leu Val Pro Arg Gly Ser His

515 520 525

His His His His His Ser Ala Trp Ser His Pro Gln Phe Glu Lys

530 535 540

<210> 17

<211> 543

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 17

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Gly Ile Leu His Tyr Glu Lys Leu Ser Lys Ile

20 25 30

Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro

35 40 45

Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn Val Ser Asn Met

50 55 60

Ser Gln Cys Thr Gly Ser Val Met Glu Asn Tyr Lys Thr Arg Leu Asn

65 70 75 80

Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile Tyr Lys Asn Asn

85 90 95

Thr His Asp Leu Val Gly Asp Val Arg Leu Ala Gly Val Cys Met Ala

100 105 110

Gly Val Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile Thr Ala Gly Val

115 120 125

Ala Leu Tyr Glu Ala Met Lys Asn Ala Asp Asn Ile Asn Lys Leu Lys

130 135 140

Ser Ser Ile Glu Ser Thr Asn Glu Ala Val Val Lys Leu Gln Glu Thr

145 150 155 160

Ala Glu Lys Thr Val Tyr Val Phe Thr Ala Leu Gln Asp Tyr Ile Asn

165 170 175

Thr Asn Leu Val Pro Thr Ile Asp Lys Ile Ser Cys Lys Gln Thr Glu

180 185 190

Leu Ser Leu Asp Leu Ala Leu Ser Lys Tyr Leu Ser Asp Leu Leu Phe

195 200 205

Val Phe Gly Pro Asn Leu Gln Asp Pro Val Ser Asn Ser Met Thr Ile

210 215 220

Gln Ala Ile Ser Gln Ala Phe Gly Gly Asn Tyr Glu Thr Leu Leu Arg

225 230 235 240

Thr Leu Gly Tyr Ala Thr Glu Asp Phe Asp Asp Leu Leu Glu Ser Asp

245 250 255

Ser Ile Thr Gly Gln Ile Ile Tyr Val Asp Leu Ser Ser Tyr Tyr Ile

260 265 270

Ile Val Arg Val Tyr Phe Pro Ile Leu Thr Glu Ile Gln Gln Ala Tyr

275 280 285

Ile Gln Glu Leu Leu Pro Val Ser Phe Asn Asn Asp Asn Ser Glu Trp

290 295 300

Ile Ser Ile Val Pro Asn Phe Ile Leu Val Arg Asn Thr Leu Ile Ser

305 310 315 320

Asn Ile Glu Ile Gly Phe Cys Leu Ile Thr Lys Arg Ser Val Ile Cys

325 330 335

Asn Gln Asp Tyr Ala Thr Pro Met Thr Asn Asn Met Arg Glu Cys Leu

340 345 350

Thr Gly Ser Thr Glu Lys Cys Pro Arg Glu Leu Val Val Ser Ser His

355 360 365

Val Pro Arg Phe Ala Leu Ser Asn Gly Val Leu Phe Ala Asn Cys Ile

370 375 380

Ser Val Thr Cys Gln Cys Gln Thr Thr Gly Arg Ala Ile Ser Gln Ser

385 390 395 400

Gly Glu Gln Thr Leu Leu Met Ile Asp Asn Thr Thr Cys Pro Thr Ala

405 410 415

Val Leu Gly Asn Val Cys Ile Ser Leu Gly Lys Tyr Leu Gly Ser Val

420 425 430

Asn Tyr Asn Ser Glu Gly Ile Ala Ile Gly Pro Pro Val Phe Thr Asp

435 440 445

Lys Val Asp Ile Ser Ser Gln Ile Ser Ser Met Asn Gln Ser Leu Gln

450 455 460

Gln Ser Lys Asp Tyr Ile Lys Glu Ala Gln Arg Leu Leu Asp Thr Val

465 470 475 480

Asn Pro Ser Leu Lys Leu Met Lys Gln Ile Glu Asp Lys Ile Glu Glu

485 490 495

Ile Leu Ser Lys Ile Tyr His Ile Glu Asn Glu Ile Ala Arg Ile Lys

500 505 510

Lys Leu Ile Gly Glu Ala Pro Gly Gly Leu Val Pro Arg Gly Ser His

515 520 525

His His His His His Ser Ala Trp Ser His Pro Gln Phe Glu Lys

530 535 540

<210> 18

<211> 543

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 18

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Gly Ile Leu His Tyr Glu Lys Leu Ser Lys Ile

20 25 30

Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro

35 40 45

Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn Val Ser Asn Met

50 55 60

Ser Gln Cys Thr Gly Ser Val Met Glu Asn Tyr Lys Thr Arg Leu Asn

65 70 75 80

Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile Tyr Lys Asn Asn

85 90 95

Thr His Asp Cys Val Gly Asp Val Arg Leu Ala Gly Val Cys Met Ala

100 105 110

Gly Val Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile Thr Ala Gly Val

115 120 125

Ala Leu Tyr Glu Ala Met Lys Asn Ala Asp Asn Ile Asn Lys Leu Lys

130 135 140

Ser Ser Ile Glu Ser Thr Asn Glu Ala Val Val Lys Leu Gln Glu Thr

145 150 155 160

Ala Glu Lys Thr Val Tyr Val Phe Thr Ala Leu Gln Asp Tyr Ile Asn

165 170 175

Thr Asn Leu Val Pro Thr Ile Asp Lys Ile Ser Cys Lys Gln Thr Glu

180 185 190

Leu Ser Leu Asp Leu Ala Leu Ser Lys Tyr Leu Ser Asp Leu Leu Phe

195 200 205

Val Phe Gly Pro Asn Leu Gln Asp Pro Val Ser Asn Ser Met Thr Ile

210 215 220

Gln Ala Ile Ser Gln Ala Phe Gly Gly Asn Tyr Glu Thr Leu Leu Arg

225 230 235 240

Thr Leu Gly Tyr Ala Thr Glu Asp Phe Asp Asp Leu Leu Glu Ser Asp

245 250 255

Ser Ile Thr Gly Gln Ile Ile Tyr Val Asp Leu Ser Ser Tyr Tyr Ile

260 265 270

Ile Val Arg Val Tyr Phe Pro Ile Leu Thr Glu Ile Gln Gln Ala Tyr

275 280 285

Ile Gln Glu Leu Leu Pro Val Ser Phe Asn Asn Asp Asn Ser Glu Trp

290 295 300

Ile Ser Ile Val Pro Asn Phe Ile Leu Val Arg Asn Thr Leu Ile Ser

305 310 315 320

Asn Ile Glu Ile Gly Phe Cys Leu Ile Thr Lys Arg Ser Val Ile Cys

325 330 335

Asn Gln Asp Tyr Ala Thr Pro Met Thr Asn Asn Met Arg Glu Cys Leu

340 345 350

Thr Gly Ser Thr Glu Lys Cys Pro Arg Glu Leu Val Val Ser Ser His

355 360 365

Val Pro Arg Phe Ala Leu Ser Asn Gly Val Leu Phe Ala Asn Cys Ile

370 375 380

Ser Val Thr Cys Gln Cys Gln Thr Thr Gly Arg Ala Ile Ser Gln Ser

385 390 395 400

Gly Glu Gln Thr Leu Leu Met Ile Asp Asn Thr Thr Cys Pro Thr Ala

405 410 415

Val Leu Gly Asn Val Ile Ile Ser Leu Gly Lys Tyr Leu Gly Ser Val

420 425 430

Asn Tyr Asn Ser Glu Gly Ile Ala Ile Gly Pro Pro Val Phe Thr Asp

435 440 445

Lys Val Asp Ile Ser Ser Gln Ile Ser Ser Met Asn Gln Ser Leu Gln

450 455 460

Gln Ser Lys Asp Tyr Ile Lys Glu Ala Gln Arg Leu Leu Asp Thr Val

465 470 475 480

Asn Pro Ser Leu Lys Leu Met Lys Gln Ile Glu Asp Lys Ile Glu Glu

485 490 495

Ile Leu Ser Lys Ile Tyr His Ile Glu Asn Glu Ile Ala Arg Ile Lys

500 505 510

Lys Leu Ile Gly Glu Ala Pro Gly Gly Leu Val Pro Arg Gly Ser His

515 520 525

His His His His His Ser Ala Trp Ser His Pro Gln Phe Glu Lys

530 535 540

<210> 19

<211> 534

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 19

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Gly Ile Leu His Tyr Glu Lys Leu Ser Lys Ile

20 25 30

Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro

35 40 45

Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn Val Ser Asn Met

50 55 60

Ser Gln Cys Thr Gly Ser Val Met Glu Asn Tyr Lys Thr Arg Leu Asn

65 70 75 80

Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile Tyr Lys Asn Asn

85 90 95

Thr Gly Ser Gly Ile Met Ala Gly Val Ala Ile Gly Ile Ala Thr Ala

100 105 110

Ala Gln Ile Thr Ala Gly Val Ala Leu Tyr Glu Ala Met Lys Asn Ala

115 120 125

Asp Asn Ile Asn Lys Leu Lys Ser Ser Ile Glu Ser Thr Asn Glu Ala

130 135 140

Val Val Lys Leu Gln Glu Thr Ala Glu Lys Thr Val Tyr Val Phe Thr

145 150 155 160

Ala Leu Gln Asp Tyr Ile Asn Thr Asn Leu Val Pro Thr Ile Asp Lys

165 170 175

Ile Ser Cys Lys Gln Thr Glu Leu Ser Leu Asp Leu Ala Leu Ser Lys

180 185 190

Tyr Leu Ser Asp Leu Leu Phe Val Phe Gly Pro Asn Leu Gln Asp Pro

195 200 205

Val Ser Asn Ser Met Thr Ile Gln Ala Ile Ser Gln Ala Phe Gly Gly

210 215 220

Asn Tyr Glu Thr Leu Leu Arg Thr Leu Gly Tyr Ala Thr Glu Asp Phe

225 230 235 240

Asp Asp Leu Leu Glu Ser Asp Ser Ile Thr Gly Gln Ile Ile Tyr Val

245 250 255

Asp Leu Ser Ser Tyr Tyr Ile Ile Val Arg Val Tyr Phe Pro Ile Leu

260 265 270

Thr Glu Ile Gln Gln Ala Tyr Ile Gln Glu Leu Leu Pro Val Ser Phe

275 280 285

Asn Asn Asp Asn Ser Glu Trp Ile Ser Ile Val Pro Asn Phe Ile Leu

290 295 300

Val Arg Asn Thr Leu Ile Ser Asn Ile Glu Ile Gly Phe Cys Leu Ile

305 310 315 320

Thr Lys Arg Ser Val Ile Cys Asn Gln Asp Tyr Ala Thr Pro Met Thr

325 330 335

Asn Asn Met Arg Glu Cys Leu Thr Gly Ser Thr Glu Lys Cys Pro Arg

340 345 350

Glu Leu Val Val Ser Ser His Val Pro Arg Phe Ala Leu Ser Asn Gly

355 360 365

Val Leu Phe Ala Asn Cys Ile Ser Val Thr Cys Gln Cys Gln Thr Thr

370 375 380

Gly Arg Ala Ile Ser Gln Ser Gly Glu Gln Thr Leu Leu Met Ile Asp

385 390 395 400

Asn Thr Thr Cys Pro Thr Ala Val Leu Gly Asn Val Ile Ile Ser Leu

405 410 415

Gly Lys Tyr Leu Gly Ser Val Asn Tyr Asn Ser Glu Gly Ile Ala Ile

420 425 430

Gly Pro Pro Val Phe Thr Asp Lys Val Asp Ile Ser Ser Gln Ile Ser

435 440 445

Ser Met Asn Gln Ser Leu Gln Gln Ser Lys Asp Tyr Ile Lys Glu Ala

450 455 460

Gln Arg Leu Leu Asp Thr Val Asn Pro Ser Leu Lys Leu Met Lys Gln

465 470 475 480

Ile Glu Asp Lys Ile Glu Glu Ile Leu Ser Lys Ile Tyr His Ile Glu

485 490 495

Asn Glu Ile Ala Arg Ile Lys Lys Leu Ile Gly Glu Ala Pro Gly Gly

500 505 510

Leu Val Pro Arg Gly Ser His His His His His His Ser Ala Trp Ser

515 520 525

His Pro Gln Phe Glu Lys

530

<210> 20

<211> 543

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 20

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Gly Ile Leu His Tyr Glu Lys Leu Ser Lys Ile

20 25 30

Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro

35 40 45

Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn Val Ser Asn Met

50 55 60

Ser Gln Cys Thr Gly Ser Val Met Glu Asn Tyr Lys Thr Arg Leu Asn

65 70 75 80

Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile Tyr Lys Asn Asn

85 90 95

Thr His Asp Leu Val Gly Asp Val Arg Leu Ala Gly Val Cys Met Ala

100 105 110

Gly Val Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile Thr Ala Gly Val

115 120 125

Ala Leu Tyr Glu Ala Met Lys Asn Ala Asp Asn Ile Asn Lys Leu Lys

130 135 140

Ser Ser Ile Glu Ser Thr Asn Glu Ala Val Val Lys Leu Gln Glu Thr

145 150 155 160

Ala Glu Lys Thr Val Tyr Val Leu Thr Ala Leu Gln Asp Tyr Ile Asn

165 170 175

Thr Asn Leu Val Pro Thr Ile Asp Lys Ile Pro Cys Lys Gln Thr Glu

180 185 190

Leu Ser Leu Asp Leu Ala Leu Ser Lys Tyr Leu Ser Asp Leu Leu Phe

195 200 205

Val Phe Gly Pro Asn Leu Gln Asp Pro Val Ser Asn Ser Met Thr Ile

210 215 220

Gln Ala Ile Ser Gln Ala Phe Gly Gly Asn Tyr Glu Thr Leu Leu Arg

225 230 235 240

Thr Leu Gly Tyr Ala Thr Glu Asp Phe Asp Asp Leu Leu Glu Ser Asp

245 250 255

Ser Ile Thr Gly Gln Ile Ile Tyr Val Asp Leu Ser Ser Tyr Tyr Ile

260 265 270

Ile Val Arg Val Tyr Phe Pro Ile Leu Thr Glu Ile Gln Gln Ala Tyr

275 280 285

Ile Gln Glu Leu Leu Pro Val Ser Phe Asn Asn Asp Asn Ser Glu Trp

290 295 300

Ile Ser Ile Val Pro Asn Phe Ile Leu Val Arg Asn Thr Leu Ile Ser

305 310 315 320

Asn Ile Glu Ile Gly Phe Cys Leu Ile Thr Lys Arg Ser Val Ile Cys

325 330 335

Asn Gln Asp Tyr Ala Thr Pro Met Thr Asn Asn Met Arg Glu Cys Leu

340 345 350

Thr Gly Ser Thr Glu Lys Cys Pro Arg Glu Leu Val Val Ser Ser His

355 360 365

Val Pro Arg Phe Ala Leu Ser Asn Gly Val Leu Phe Ala Asn Cys Ile

370 375 380

Ser Val Thr Cys Gln Cys Gln Thr Thr Gly Arg Ala Ile Ser Gln Ser

385 390 395 400

Gly Glu Gln Thr Leu Leu Met Ile Asp Asn Thr Thr Cys Pro Thr Ala

405 410 415

Val Leu Gly Asn Val Cys Ile Ser Leu Gly Lys Tyr Leu Gly Ser Val

420 425 430

Asn Tyr Asn Ser Glu Gly Ile Ala Ile Gly Pro Pro Val Phe Thr Asp

435 440 445

Lys Val Asp Ile Ser Ser Gln Ile Ser Ser Met Asn Gln Ser Leu Gln

450 455 460

Gln Ser Lys Asp Tyr Ile Lys Glu Ala Gln Arg Leu Leu Asp Thr Val

465 470 475 480

Asn Pro Ser Leu Lys Leu Met Lys Gln Ile Glu Asp Lys Ile Glu Glu

485 490 495

Ile Leu Ser Lys Ile Tyr His Ile Glu Asn Glu Ile Ala Arg Ile Lys

500 505 510

Lys Leu Ile Gly Glu Ala Pro Gly Gly Leu Val Pro Arg Gly Ser His

515 520 525

His His His His His Ser Ala Trp Ser His Pro Gln Phe Glu Lys

530 535 540

<210> 21

<211> 543

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 21

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Gly Ile Leu His Tyr Glu Lys Leu Ser Lys Ile

20 25 30

Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro

35 40 45

Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn Val Ser Asn Met

50 55 60

Ser Gln Cys Thr Gly Ser Val Met Glu Asn Tyr Lys Thr Arg Leu Asn

65 70 75 80

Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile Tyr Lys Asn Asn

85 90 95

Thr His Asp Cys Val Gly Asp Val Arg Leu Ala Gly Val Cys Met Ala

100 105 110

Gly Val Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile Thr Ala Gly Val

115 120 125

Ala Leu Tyr Glu Ala Met Lys Asn Ala Asp Asn Ile Asn Lys Leu Lys

130 135 140

Ser Ser Ile Glu Ser Thr Asn Glu Ala Val Val Lys Leu Gln Glu Thr

145 150 155 160

Ala Glu Lys Thr Val Tyr Val Leu Thr Ala Leu Gln Asp Tyr Ile Asn

165 170 175

Thr Asn Leu Val Pro Thr Ile Asp Lys Ile Pro Cys Lys Gln Thr Glu

180 185 190

Leu Ser Leu Asp Leu Ala Leu Ser Lys Tyr Leu Ser Asp Leu Leu Phe

195 200 205

Val Phe Gly Pro Asn Leu Gln Asp Pro Val Ser Asn Ser Met Thr Ile

210 215 220

Gln Ala Ile Ser Gln Ala Phe Gly Gly Asn Tyr Glu Thr Leu Leu Arg

225 230 235 240

Thr Leu Gly Tyr Ala Thr Glu Asp Phe Asp Asp Leu Leu Glu Ser Asp

245 250 255

Ser Ile Thr Gly Gln Ile Ile Tyr Val Asp Leu Ser Ser Tyr Tyr Ile

260 265 270

Ile Val Arg Val Tyr Phe Pro Ile Leu Thr Glu Ile Gln Gln Ala Tyr

275 280 285

Ile Gln Glu Leu Leu Pro Val Ser Phe Asn Asn Asp Asn Ser Glu Trp

290 295 300

Ile Ser Ile Val Pro Asn Phe Ile Leu Val Arg Asn Thr Leu Ile Ser

305 310 315 320

Asn Ile Glu Ile Gly Phe Cys Leu Ile Thr Lys Arg Ser Val Ile Cys

325 330 335

Asn Gln Asp Tyr Ala Thr Pro Met Thr Asn Asn Met Arg Glu Cys Leu

340 345 350

Thr Gly Ser Thr Glu Lys Cys Pro Arg Glu Leu Val Val Ser Ser His

355 360 365

Val Pro Arg Phe Ala Leu Ser Asn Gly Val Leu Phe Ala Asn Cys Ile

370 375 380

Ser Val Thr Cys Gln Cys Gln Thr Thr Gly Arg Ala Ile Ser Gln Ser

385 390 395 400

Gly Glu Gln Thr Leu Leu Met Ile Asp Asn Thr Thr Cys Pro Thr Ala

405 410 415

Val Leu Gly Asn Val Ile Ile Ser Leu Gly Lys Tyr Leu Gly Ser Val

420 425 430

Asn Tyr Asn Ser Glu Gly Ile Ala Ile Gly Pro Pro Val Phe Thr Asp

435 440 445

Lys Val Asp Ile Ser Ser Gln Ile Ser Ser Met Asn Gln Ser Leu Gln

450 455 460

Gln Ser Lys Asp Tyr Ile Lys Glu Ala Gln Arg Leu Leu Asp Thr Val

465 470 475 480

Asn Pro Ser Leu Lys Leu Met Lys Gln Ile Glu Asp Lys Ile Glu Glu

485 490 495

Ile Leu Ser Lys Ile Tyr His Ile Glu Asn Glu Ile Ala Arg Ile Lys

500 505 510

Lys Leu Ile Gly Glu Ala Pro Gly Gly Leu Val Pro Arg Gly Ser His

515 520 525

His His His His His Ser Ala Trp Ser His Pro Gln Phe Glu Lys

530 535 540

<210> 22

<211> 534

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 22

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Gly Ile Leu His Tyr Glu Lys Leu Ser Lys Ile

20 25 30

Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro

35 40 45

Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn Val Ser Asn Met

50 55 60

Ser Gln Cys Thr Gly Ser Val Met Glu Asn Tyr Lys Thr Arg Leu Asn

65 70 75 80

Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile Tyr Lys Asn Asn

85 90 95

Thr Gly Ser Gly Ile Met Ala Gly Val Ala Ile Gly Ile Ala Thr Ala

100 105 110

Ala Gln Ile Thr Ala Gly Val Ala Leu Tyr Glu Ala Met Lys Asn Ala

115 120 125

Asp Asn Ile Asn Lys Leu Lys Ser Ser Ile Glu Ser Thr Asn Glu Ala

130 135 140

Val Val Lys Leu Gln Glu Thr Ala Glu Lys Thr Val Tyr Val Leu Thr

145 150 155 160

Ala Leu Gln Asp Tyr Ile Asn Thr Asn Leu Val Pro Thr Ile Asp Lys

165 170 175

Ile Pro Cys Lys Gln Thr Glu Leu Ser Leu Asp Leu Ala Leu Ser Lys

180 185 190

Tyr Leu Ser Asp Leu Leu Phe Val Phe Gly Pro Asn Leu Gln Asp Pro

195 200 205

Val Ser Asn Ser Met Thr Ile Gln Ala Ile Ser Gln Ala Phe Gly Gly

210 215 220

Asn Tyr Glu Thr Leu Leu Arg Thr Leu Gly Tyr Ala Thr Glu Asp Phe

225 230 235 240

Asp Asp Leu Leu Glu Ser Asp Ser Ile Thr Gly Gln Ile Ile Tyr Val

245 250 255

Asp Leu Ser Ser Tyr Tyr Ile Ile Val Arg Val Tyr Phe Pro Ile Leu

260 265 270

Thr Glu Ile Gln Gln Ala Tyr Ile Gln Glu Leu Leu Pro Val Ser Phe

275 280 285

Asn Asn Asp Asn Ser Glu Trp Ile Ser Ile Val Pro Asn Phe Ile Leu

290 295 300

Val Arg Asn Thr Leu Ile Ser Asn Ile Glu Ile Gly Phe Cys Leu Ile

305 310 315 320

Thr Lys Arg Ser Val Ile Cys Asn Gln Asp Tyr Ala Thr Pro Met Thr

325 330 335

Asn Asn Met Arg Glu Cys Leu Thr Gly Ser Thr Glu Lys Cys Pro Arg

340 345 350

Glu Leu Val Val Ser Ser His Val Pro Arg Phe Ala Leu Ser Asn Gly

355 360 365

Val Leu Phe Ala Asn Cys Ile Ser Val Thr Cys Gln Cys Gln Thr Thr

370 375 380

Gly Arg Ala Ile Ser Gln Ser Gly Glu Gln Thr Leu Leu Met Ile Asp

385 390 395 400

Asn Thr Thr Cys Pro Thr Ala Val Leu Gly Asn Val Ile Ile Ser Leu

405 410 415

Gly Lys Tyr Leu Gly Ser Val Asn Tyr Asn Ser Glu Gly Ile Ala Ile

420 425 430

Gly Pro Pro Val Phe Thr Asp Lys Val Asp Ile Ser Ser Gln Ile Ser

435 440 445

Ser Met Asn Gln Ser Leu Gln Gln Ser Lys Asp Tyr Ile Lys Glu Ala

450 455 460

Gln Arg Leu Leu Asp Thr Val Asn Pro Ser Leu Lys Leu Met Lys Gln

465 470 475 480

Ile Glu Asp Lys Ile Glu Glu Ile Leu Ser Lys Ile Tyr His Ile Glu

485 490 495

Asn Glu Ile Ala Arg Ile Lys Lys Leu Ile Gly Glu Ala Pro Gly Gly

500 505 510

Leu Val Pro Arg Gly Ser His His His His His His Ser Ala Trp Ser

515 520 525

His Pro Gln Phe Glu Lys

530

<210> 23

<211> 543

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 23

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Gly Ile Leu His Tyr Glu Lys Leu Ser Lys Ile

20 25 30

Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro

35 40 45

Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn Val Ser Asn Met

50 55 60

Ser Gln Cys Thr Gly Ser Val Met Glu Asn Tyr Lys Thr Arg Leu Asn

65 70 75 80

Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile Tyr Lys Asn Asn

85 90 95

Thr His Asp Leu Val Gly Asp Val Arg Leu Ala Gly Val Cys Met Ala

100 105 110

Gly Val Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile Thr Ala Gly Val

115 120 125

Ala Leu Tyr Glu Ala Met Lys Asn Ala Asp Asn Ile Asn Lys Leu Lys

130 135 140

Ser Ser Ile Glu Ser Thr Asn Glu Ala Val Val Lys Leu Gln Glu Thr

145 150 155 160

Ala Glu Lys Thr Val Tyr Val Phe Thr Ala Leu Gln Asp Tyr Ile Asn

165 170 175

Thr Asn Leu Val Pro Thr Ile Asp Lys Ile Pro Cys Lys Gln Thr Glu

180 185 190

Leu Ser Leu Asp Leu Ala Leu Ser Lys Tyr Leu Ser Asp Leu Leu Phe

195 200 205

Val Phe Gly Pro Asn Leu Gln Asp Pro Val Ser Asn Ser Met Thr Ile

210 215 220

Gln Ala Ile Ser Gln Ala Phe Gly Gly Asn Tyr Glu Thr Leu Leu Arg

225 230 235 240

Thr Leu Gly Tyr Ala Thr Glu Asp Phe Asp Asp Leu Leu Glu Ser Asp

245 250 255

Ser Ile Thr Gly Gln Ile Ile Tyr Val Asp Leu Ser Ser Tyr Tyr Ile

260 265 270

Ile Val Arg Val Tyr Phe Pro Ile Leu Thr Glu Ile Gln Gln Ala Tyr

275 280 285

Ile Gln Glu Leu Leu Pro Val Ser Phe Asn Asn Asp Asn Ser Glu Trp

290 295 300

Ile Ser Ile Val Pro Asn Phe Ile Leu Val Arg Asn Thr Leu Ile Ser

305 310 315 320

Asn Ile Glu Ile Gly Phe Cys Leu Ile Thr Lys Arg Ser Val Ile Cys

325 330 335

Asn Gln Asp Tyr Ala Thr Pro Met Thr Asn Asn Met Arg Glu Cys Leu

340 345 350

Thr Gly Ser Thr Glu Lys Cys Pro Arg Glu Leu Val Val Ser Ser His

355 360 365

Val Pro Arg Phe Ala Leu Ser Asn Gly Val Leu Phe Ala Asn Cys Ile

370 375 380

Ser Val Thr Cys Gln Cys Gln Thr Thr Gly Arg Ala Ile Ser Gln Ser

385 390 395 400

Gly Glu Gln Thr Leu Leu Met Ile Asp Asn Thr Thr Cys Pro Thr Ala

405 410 415

Val Leu Gly Asn Val Cys Ile Ser Leu Gly Lys Tyr Leu Gly Ser Val

420 425 430

Asn Tyr Asn Ser Glu Gly Ile Ala Ile Gly Pro Pro Val Phe Thr Asp

435 440 445

Lys Val Asp Ile Ser Ser Gln Ile Ser Ser Met Asn Gln Ser Leu Gln

450 455 460

Gln Ser Lys Asp Tyr Ile Lys Glu Ala Gln Arg Leu Leu Asp Thr Val

465 470 475 480

Asn Pro Ser Leu Lys Leu Met Lys Gln Ile Glu Asp Lys Ile Glu Glu

485 490 495

Ile Leu Ser Lys Ile Tyr His Ile Glu Asn Glu Ile Ala Arg Ile Lys

500 505 510

Lys Leu Ile Gly Glu Ala Pro Gly Gly Leu Val Pro Arg Gly Ser His

515 520 525

His His His His His Ser Ala Trp Ser His Pro Gln Phe Glu Lys

530 535 540

<210> 24

<211> 543

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 24

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Gly Ile Leu His Tyr Glu Lys Leu Ser Lys Ile

20 25 30

Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro

35 40 45

Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn Val Ser Asn Met

50 55 60

Ser Gln Cys Thr Gly Ser Val Met Glu Asn Tyr Lys Thr Arg Leu Asn

65 70 75 80

Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile Tyr Lys Asn Asn

85 90 95

Thr His Asp Cys Val Gly Asp Val Arg Leu Ala Gly Val Cys Met Ala

100 105 110

Gly Val Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile Thr Ala Gly Val

115 120 125

Ala Leu Tyr Glu Ala Met Lys Asn Ala Asp Asn Ile Asn Lys Leu Lys

130 135 140

Ser Ser Ile Glu Ser Thr Asn Glu Ala Val Val Lys Leu Gln Glu Thr

145 150 155 160

Ala Glu Lys Thr Val Tyr Val Phe Thr Ala Leu Gln Asp Tyr Ile Asn

165 170 175

Thr Asn Leu Val Pro Thr Ile Asp Lys Ile Pro Cys Lys Gln Thr Glu

180 185 190

Leu Ser Leu Asp Leu Ala Leu Ser Lys Tyr Leu Ser Asp Leu Leu Phe

195 200 205

Val Phe Gly Pro Asn Leu Gln Asp Pro Val Ser Asn Ser Met Thr Ile

210 215 220

Gln Ala Ile Ser Gln Ala Phe Gly Gly Asn Tyr Glu Thr Leu Leu Arg

225 230 235 240

Thr Leu Gly Tyr Ala Thr Glu Asp Phe Asp Asp Leu Leu Glu Ser Asp

245 250 255

Ser Ile Thr Gly Gln Ile Ile Tyr Val Asp Leu Ser Ser Tyr Tyr Ile

260 265 270

Ile Val Arg Val Tyr Phe Pro Ile Leu Thr Glu Ile Gln Gln Ala Tyr

275 280 285

Ile Gln Glu Leu Leu Pro Val Ser Phe Asn Asn Asp Asn Ser Glu Trp

290 295 300

Ile Ser Ile Val Pro Asn Phe Ile Leu Val Arg Asn Thr Leu Ile Ser

305 310 315 320

Asn Ile Glu Ile Gly Phe Cys Leu Ile Thr Lys Arg Ser Val Ile Cys

325 330 335

Asn Gln Asp Tyr Ala Thr Pro Met Thr Asn Asn Met Arg Glu Cys Leu

340 345 350

Thr Gly Ser Thr Glu Lys Cys Pro Arg Glu Leu Val Val Ser Ser His

355 360 365

Val Pro Arg Phe Ala Leu Ser Asn Gly Val Leu Phe Ala Asn Cys Ile

370 375 380

Ser Val Thr Cys Gln Cys Gln Thr Thr Gly Arg Ala Ile Ser Gln Ser

385 390 395 400

Gly Glu Gln Thr Leu Leu Met Ile Asp Asn Thr Thr Cys Pro Thr Ala

405 410 415

Val Leu Gly Asn Val Ile Ile Ser Leu Gly Lys Tyr Leu Gly Ser Val

420 425 430

Asn Tyr Asn Ser Glu Gly Ile Ala Ile Gly Pro Pro Val Phe Thr Asp

435 440 445

Lys Val Asp Ile Ser Ser Gln Ile Ser Ser Met Asn Gln Ser Leu Gln

450 455 460

Gln Ser Lys Asp Tyr Ile Lys Glu Ala Gln Arg Leu Leu Asp Thr Val

465 470 475 480

Asn Pro Ser Leu Lys Leu Met Lys Gln Ile Glu Asp Lys Ile Glu Glu

485 490 495

Ile Leu Ser Lys Ile Tyr His Ile Glu Asn Glu Ile Ala Arg Ile Lys

500 505 510

Lys Leu Ile Gly Glu Ala Pro Gly Gly Leu Val Pro Arg Gly Ser His

515 520 525

His His His His His Ser Ala Trp Ser His Pro Gln Phe Glu Lys

530 535 540

<210> 25

<211> 534

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 25

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Gly Ile Leu His Tyr Glu Lys Leu Ser Lys Ile

20 25 30

Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro

35 40 45

Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn Val Ser Asn Met

50 55 60

Ser Gln Cys Thr Gly Ser Val Met Glu Asn Tyr Lys Thr Arg Leu Asn

65 70 75 80

Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile Tyr Lys Asn Asn

85 90 95

Thr Gly Ser Gly Ile Met Ala Gly Val Ala Ile Gly Ile Ala Thr Ala

100 105 110

Ala Gln Ile Thr Ala Gly Val Ala Leu Tyr Glu Ala Met Lys Asn Ala

115 120 125

Asp Asn Ile Asn Lys Leu Lys Ser Ser Ile Glu Ser Thr Asn Glu Ala

130 135 140

Val Val Lys Leu Gln Glu Thr Ala Glu Lys Thr Val Tyr Val Phe Thr

145 150 155 160

Ala Leu Gln Asp Tyr Ile Asn Thr Asn Leu Val Pro Thr Ile Asp Lys

165 170 175

Ile Pro Cys Lys Gln Thr Glu Leu Ser Leu Asp Leu Ala Leu Ser Lys

180 185 190

Tyr Leu Ser Asp Leu Leu Phe Val Phe Gly Pro Asn Leu Gln Asp Pro

195 200 205

Val Ser Asn Ser Met Thr Ile Gln Ala Ile Ser Gln Ala Phe Gly Gly

210 215 220

Asn Tyr Glu Thr Leu Leu Arg Thr Leu Gly Tyr Ala Thr Glu Asp Phe

225 230 235 240

Asp Asp Leu Leu Glu Ser Asp Ser Ile Thr Gly Gln Ile Ile Tyr Val

245 250 255

Asp Leu Ser Ser Tyr Tyr Ile Ile Val Arg Val Tyr Phe Pro Ile Leu

260 265 270

Thr Glu Ile Gln Gln Ala Tyr Ile Gln Glu Leu Leu Pro Val Ser Phe

275 280 285

Asn Asn Asp Asn Ser Glu Trp Ile Ser Ile Val Pro Asn Phe Ile Leu

290 295 300

Val Arg Asn Thr Leu Ile Ser Asn Ile Glu Ile Gly Phe Cys Leu Ile

305 310 315 320

Thr Lys Arg Ser Val Ile Cys Asn Gln Asp Tyr Ala Thr Pro Met Thr

325 330 335

Asn Asn Met Arg Glu Cys Leu Thr Gly Ser Thr Glu Lys Cys Pro Arg

340 345 350

Glu Leu Val Val Ser Ser His Val Pro Arg Phe Ala Leu Ser Asn Gly

355 360 365

Val Leu Phe Ala Asn Cys Ile Ser Val Thr Cys Gln Cys Gln Thr Thr

370 375 380

Gly Arg Ala Ile Ser Gln Ser Gly Glu Gln Thr Leu Leu Met Ile Asp

385 390 395 400

Asn Thr Thr Cys Pro Thr Ala Val Leu Gly Asn Val Ile Ile Ser Leu

405 410 415

Gly Lys Tyr Leu Gly Ser Val Asn Tyr Asn Ser Glu Gly Ile Ala Ile

420 425 430

Gly Pro Pro Val Phe Thr Asp Lys Val Asp Ile Ser Ser Gln Ile Ser

435 440 445

Ser Met Asn Gln Ser Leu Gln Gln Ser Lys Asp Tyr Ile Lys Glu Ala

450 455 460

Gln Arg Leu Leu Asp Thr Val Asn Pro Ser Leu Lys Leu Met Lys Gln

465 470 475 480

Ile Glu Asp Lys Ile Glu Glu Ile Leu Ser Lys Ile Tyr His Ile Glu

485 490 495

Asn Glu Ile Ala Arg Ile Lys Lys Leu Ile Gly Glu Ala Pro Gly Gly

500 505 510

Leu Val Pro Arg Gly Ser His His His His His His Ser Ala Trp Ser

515 520 525

His Pro Gln Phe Glu Lys

530

<210> 26

<211> 543

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 26

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Gly Ile Leu His Tyr Glu Lys Leu Ser Lys Ile

20 25 30

Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro

35 40 45

Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn Val Ser Asn Met

50 55 60

Ser Gln Cys Thr Gly Ser Val Met Glu Asn Tyr Lys Thr Arg Leu Asn

65 70 75 80

Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile Tyr Lys Asn Asn

85 90 95

Thr His Asp Leu Val Gly Asp Val Arg Leu Ala Gly Val Ile Met Ala

100 105 110

Gly Val Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile Thr Ala Gly Val

115 120 125

Ala Leu Tyr Glu Ala Met Lys Asn Ala Asp Asn Ile Asn Lys Leu Lys

130 135 140

Ser Ser Ile Glu Ser Thr Asn Glu Ala Val Val Lys Leu Gln Glu Thr

145 150 155 160

Ala Glu Lys Thr Val Tyr Val Phe Thr Ala Leu Gln Asp Tyr Ile Asn

165 170 175

Thr Asn Leu Val Pro Thr Ile Asp Lys Ile Pro Cys Lys Gln Thr Glu

180 185 190

Leu Ser Leu Asp Leu Ala Leu Ser Lys Tyr Leu Ser Asp Leu Leu Phe

195 200 205

Val Phe Gly Pro Asn Leu Gln Asp Pro Val Ser Asn Ser Met Thr Ile

210 215 220

Gln Ala Ile Ser Gln Ala Phe Gly Gly Asn Tyr Glu Thr Leu Leu Arg

225 230 235 240

Thr Leu Gly Tyr Ala Thr Glu Asp Phe Asp Asp Leu Leu Glu Ser Asp

245 250 255

Ser Ile Thr Gly Gln Ile Ile Tyr Val Asp Leu Ser Ser Tyr Tyr Ile

260 265 270

Ile Val Arg Val Tyr Phe Pro Ile Leu Thr Glu Ile Gln Gln Ala Tyr

275 280 285

Ile Gln Glu Leu Leu Pro Val Ser Phe Asn Asn Asp Asn Ser Glu Trp

290 295 300

Ile Ser Ile Val Pro Asn Phe Ile Leu Val Arg Asn Thr Leu Ile Ser

305 310 315 320

Asn Ile Glu Ile Gly Phe Cys Leu Ile Thr Lys Arg Ser Val Ile Cys

325 330 335

Asn Gln Asp Tyr Ala Thr Pro Met Thr Asn Asn Met Arg Glu Cys Leu

340 345 350

Thr Gly Ser Thr Glu Lys Cys Pro Arg Glu Leu Val Val Ser Ser His

355 360 365

Val Pro Arg Phe Ala Leu Ser Asn Gly Val Leu Phe Ala Asn Cys Ile

370 375 380

Ser Val Thr Cys Gln Cys Gln Thr Thr Gly Arg Ala Ile Ser Gln Ser

385 390 395 400

Gly Glu Gln Thr Leu Leu Met Ile Asp Asn Thr Thr Cys Pro Thr Ala

405 410 415

Val Leu Gly Asn Val Ile Ile Ser Leu Gly Lys Tyr Leu Gly Ser Val

420 425 430

Asn Tyr Asn Ser Glu Gly Ile Ala Ile Gly Pro Pro Val Phe Thr Asp

435 440 445

Lys Val Asp Ile Ser Ser Gln Ile Ser Ser Met Asn Gln Ser Leu Gln

450 455 460

Gln Ser Lys Asp Tyr Ile Lys Glu Ala Gln Arg Leu Leu Asp Thr Val

465 470 475 480

Asn Pro Ser Leu Lys Leu Met Lys Gln Ile Glu Asp Lys Ile Glu Glu

485 490 495

Ile Leu Ser Lys Ile Tyr His Ile Glu Asn Glu Ile Ala Arg Ile Lys

500 505 510

Lys Leu Ile Gly Glu Ala Pro Gly Gly Leu Val Pro Arg Gly Ser His

515 520 525

His His His His His Ser Ala Trp Ser His Pro Gln Phe Glu Lys

530 535 540

<210> 27

<211> 543

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 27

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Gly Ile Leu His Tyr Glu Lys Leu Ser Lys Ile

20 25 30

Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro

35 40 45

Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn Val Ser Asn Met

50 55 60

Ser Gly Cys Thr Gly Ser Val Met Glu Asn Tyr Lys Thr Arg Leu Asn

65 70 75 80

Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile Tyr Lys Asn Asn

85 90 95

Thr His Asp Leu Val Gly Asp Val Arg Leu Ala Gly Val Ile Met Ala

100 105 110

Gly Val Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile Thr Ala Gly Val

115 120 125

Ala Leu Tyr Glu Ala Met Lys Asn Ala Asp Asn Ile Asn Lys Leu Lys

130 135 140

Ser Ser Ile Glu Ser Thr Asn Glu Ala Val Val Lys Leu Gln Glu Thr

145 150 155 160

Ala Glu Lys Thr Val Tyr Val Phe Thr Ala Leu Gln Asp Tyr Ile Asn

165 170 175

Thr Asn Leu Val Pro Thr Ile Asp Lys Ile Pro Cys Lys Gln Thr Glu

180 185 190

Leu Ser Leu Asp Leu Ala Leu Ser Lys Tyr Leu Ser Asp Leu Leu Phe

195 200 205

Val Phe Gly Pro Asn Leu Gln Asp Pro Val Ser Asn Ser Met Thr Ile

210 215 220

Gln Ala Ile Ser Gln Ala Phe Gly Gly Asn Tyr Glu Thr Leu Leu Arg

225 230 235 240

Thr Leu Gly Tyr Ala Thr Glu Asp Phe Asp Asp Leu Leu Glu Ser Asp

245 250 255

Ser Ile Thr Gly Gln Ile Ile Tyr Val Asp Leu Ser Ser Tyr Tyr Ile

260 265 270

Ile Val Arg Val Tyr Phe Pro Ile Leu Thr Glu Ile Gln Gln Ala Tyr

275 280 285

Ile Gln Glu Leu Leu Pro Val Ser Phe Asn Asn Asp Asn Ser Glu Trp

290 295 300

Ile Ser Ile Val Pro Asn Phe Ile Leu Val Arg Asn Thr Leu Ile Ser

305 310 315 320

Asn Ile Glu Ile Gly Phe Cys Leu Ile Thr Lys Arg Ser Val Ile Cys

325 330 335

Asn Gln Asp Tyr Ala Thr Pro Met Thr Asn Asn Met Arg Glu Cys Leu

340 345 350

Thr Gly Ser Thr Glu Lys Cys Pro Arg Glu Leu Val Val Ser Ser His

355 360 365

Val Pro Arg Phe Ala Leu Ser Asn Gly Val Leu Phe Ala Asn Cys Ile

370 375 380

Ser Val Thr Cys Gln Cys Gln Thr Thr Gly Arg Ala Ile Ser Gln Ser

385 390 395 400

Gly Glu Gln Thr Leu Leu Met Ile Asp Asn Thr Thr Cys Pro Thr Ala

405 410 415

Val Leu Gly Asn Val Ile Ile Ser Leu Gly Lys Tyr Leu Gly Ser Val

420 425 430

Asn Tyr Asn Ser Glu Gly Ile Ala Ile Gly Pro Pro Val Phe Thr Asp

435 440 445

Lys Val Asp Ile Ser Ser Gln Ile Ser Ser Met Asn Gln Ser Leu Gln

450 455 460

Gln Ser Lys Asp Tyr Ile Lys Glu Ala Gln Arg Leu Leu Asp Thr Val

465 470 475 480

Asn Pro Ser Leu Lys Leu Met Lys Gln Ile Glu Asp Lys Ile Glu Glu

485 490 495

Ile Leu Ser Lys Ile Tyr His Ile Glu Asn Glu Ile Ala Arg Ile Lys

500 505 510

Lys Leu Ile Gly Glu Ala Pro Gly Gly Leu Val Pro Arg Gly Ser His

515 520 525

His His His His His Ser Ala Trp Ser His Pro Gln Phe Glu Lys

530 535 540

<210> 28

<211> 543

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 28

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Gly Ile Leu His Tyr Glu Lys Leu Ser Lys Ile

20 25 30

Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro

35 40 45

Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn Val Ser Asn Met

50 55 60

Ser Gly Cys Thr Gly Ser Val Met Glu Asn Tyr Lys Thr Arg Leu Asn

65 70 75 80

Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile Tyr Lys Asn Asn

85 90 95

Thr His Asp Cys Val Gly Asp Val Arg Leu Ala Gly Val Cys Met Ala

100 105 110

Gly Val Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile Thr Ala Gly Val

115 120 125

Ala Leu Tyr Glu Ala Met Lys Asn Ala Asp Asn Ile Asn Lys Leu Lys

130 135 140

Ser Ser Ile Glu Ser Thr Asn Glu Ala Val Val Lys Leu Gln Glu Thr

145 150 155 160

Ala Glu Lys Thr Val Tyr Val Phe Thr Ala Leu Gln Asp Tyr Ile Asn

165 170 175

Thr Asn Leu Val Pro Thr Ile Asp Lys Ile Pro Cys Lys Gln Thr Glu

180 185 190

Leu Ser Leu Asp Leu Ala Leu Ser Lys Tyr Leu Ser Asp Leu Leu Phe

195 200 205

Val Phe Gly Pro Asn Leu Gln Asp Pro Val Ser Asn Ser Met Thr Ile

210 215 220

Gln Ala Ile Ser Gln Ala Phe Gly Gly Asn Tyr Glu Thr Leu Leu Arg

225 230 235 240

Thr Leu Gly Tyr Ala Thr Glu Asp Phe Asp Asp Leu Leu Glu Ser Asp

245 250 255

Ser Ile Thr Gly Gln Ile Ile Tyr Val Asp Leu Ser Ser Tyr Tyr Ile

260 265 270

Ile Val Arg Val Tyr Phe Pro Ile Leu Thr Glu Ile Gln Gln Ala Tyr

275 280 285

Ile Gln Glu Leu Leu Pro Val Ser Phe Asn Asn Asp Asn Ser Glu Trp

290 295 300

Ile Ser Ile Val Pro Asn Phe Ile Leu Val Arg Asn Thr Leu Ile Ser

305 310 315 320

Asn Ile Glu Ile Gly Phe Cys Leu Ile Thr Lys Arg Ser Val Ile Cys

325 330 335

Asn Gln Asp Tyr Ala Thr Pro Met Thr Asn Asn Met Arg Glu Cys Leu

340 345 350

Thr Gly Ser Thr Glu Lys Cys Pro Arg Glu Leu Val Val Ser Ser His

355 360 365

Val Pro Arg Phe Ala Leu Ser Asn Gly Val Leu Phe Ala Asn Cys Ile

370 375 380

Ser Val Thr Cys Gln Cys Gln Thr Thr Gly Arg Ala Ile Ser Gln Ser

385 390 395 400

Gly Glu Gln Thr Leu Leu Met Ile Asp Asn Thr Thr Cys Pro Thr Ala

405 410 415

Val Leu Gly Asn Val Ile Ile Ser Leu Gly Lys Tyr Leu Gly Ser Val

420 425 430

Asn Tyr Asn Ser Glu Gly Ile Ala Ile Gly Pro Pro Val Phe Thr Asp

435 440 445

Lys Val Asp Ile Ser Ser Gln Ile Ser Ser Met Asn Gln Ser Leu Gln

450 455 460

Gln Ser Lys Asp Tyr Ile Lys Glu Ala Gln Arg Leu Leu Asp Thr Val

465 470 475 480

Asn Pro Ser Leu Lys Leu Met Lys Gln Ile Glu Asp Lys Ile Glu Glu

485 490 495

Ile Leu Ser Lys Ile Tyr His Ile Glu Asn Glu Ile Ala Arg Ile Lys

500 505 510

Lys Leu Ile Gly Glu Ala Pro Gly Gly Leu Val Pro Arg Gly Ser His

515 520 525

His His His His His Ser Ala Trp Ser His Pro Gln Phe Glu Lys

530 535 540

<210> 29

<211> 543

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 29

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Gly Ile Leu His Tyr Glu Lys Leu Ser Lys Ile

20 25 30

Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro

35 40 45

Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn Val Ser Asn Met

50 55 60

Ser Gly Cys Thr Gly Ser Val Met Glu Asn Tyr Lys Thr Arg Leu Asn

65 70 75 80

Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile Tyr Lys Asn Asn

85 90 95

Thr His Asp Cys Val Gly Asp Val Arg Leu Ala Gly Val Cys Met Ala

100 105 110

Gly Val Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile Thr Ala Gly Val

115 120 125

Ala Leu Tyr Glu Ala Met Lys Asn Ala Asp Asn Ile Asn Lys Leu Lys

130 135 140

Ser Ser Ile Glu Ser Thr Asn Glu Ala Val Val Lys Leu Gln Glu Thr

145 150 155 160

Ala Glu Lys Thr Val Tyr Val Phe Thr Ala Leu Gln Asp Tyr Ile Asn

165 170 175

Thr Asn Leu Val Pro Thr Ile Asp Lys Ile Ser Cys Lys Gln Thr Glu

180 185 190

Leu Ser Leu Asp Leu Ala Leu Ser Lys Tyr Leu Ser Asp Leu Leu Phe

195 200 205

Val Phe Gly Pro Asn Leu Gln Asp Pro Val Ser Asn Ser Met Thr Ile

210 215 220

Gln Ala Ile Ser Gln Ala Phe Gly Gly Asn Tyr Glu Thr Leu Leu Arg

225 230 235 240

Thr Leu Gly Tyr Ala Thr Glu Asp Phe Asp Asp Leu Leu Glu Ser Asp

245 250 255

Ser Ile Thr Gly Gln Ile Ile Tyr Val Asp Leu Ser Ser Tyr Tyr Ile

260 265 270

Ile Val Arg Val Tyr Phe Pro Ile Leu Thr Glu Ile Gln Gln Ala Tyr

275 280 285

Ile Gln Glu Leu Leu Pro Val Ser Phe Asn Asn Asp Asn Ser Glu Trp

290 295 300

Ile Ser Ile Val Pro Asn Phe Ile Leu Val Arg Asn Thr Leu Ile Ser

305 310 315 320

Asn Ile Glu Ile Gly Phe Cys Leu Ile Thr Lys Arg Ser Val Ile Cys

325 330 335

Asn Gln Asp Tyr Ala Thr Pro Met Thr Asn Asn Met Arg Glu Cys Leu

340 345 350

Thr Gly Ser Thr Glu Lys Cys Pro Arg Glu Leu Val Val Ser Ser His

355 360 365

Val Pro Arg Phe Ala Leu Ser Asn Gly Val Leu Phe Ala Asn Cys Ile

370 375 380

Ser Val Thr Cys Gln Cys Gln Thr Thr Gly Arg Ala Ile Ser Gln Ser

385 390 395 400

Gly Glu Gln Thr Leu Leu Met Ile Asp Asn Thr Thr Cys Pro Thr Ala

405 410 415

Val Leu Gly Asn Val Ile Ile Ser Leu Gly Lys Tyr Leu Gly Ser Val

420 425 430

Asn Tyr Asn Ser Glu Gly Ile Ala Ile Gly Pro Pro Val Phe Thr Asp

435 440 445

Lys Val Asp Ile Ser Ser Gln Ile Ser Ser Met Asn Gln Ser Leu Gln

450 455 460

Gln Ser Lys Asp Tyr Ile Lys Glu Ala Gln Arg Leu Leu Asp Thr Val

465 470 475 480

Asn Pro Ser Leu Lys Leu Met Lys Gln Ile Glu Asp Lys Ile Glu Glu

485 490 495

Ile Leu Ser Lys Ile Tyr His Ile Glu Asn Glu Ile Ala Arg Ile Lys

500 505 510

Lys Leu Ile Gly Glu Ala Pro Gly Gly Leu Val Pro Arg Gly Ser His

515 520 525

His His His His His Ser Ala Trp Ser His Pro Gln Phe Glu Lys

530 535 540

<210> 30

<211> 543

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 30

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Gly Ile Leu His Tyr Glu Lys Leu Ser Lys Ile

20 25 30

Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro

35 40 45

Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn Val Ser Asn Met

50 55 60

Ser Gly Cys Thr Gly Ser Val Met Glu Asn Tyr Lys Thr Arg Leu Asn

65 70 75 80

Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile Tyr Lys Asn Asn

85 90 95

Thr His Asp Cys Val Gly Asp Val Arg Leu Ala Gly Val Cys Met Ala

100 105 110

Gly Val Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile Thr Ala Gly Val

115 120 125

Ala Leu Tyr Glu Ala Met Lys Asn Ala Asp Asn Ile Asn Lys Leu Lys

130 135 140

Ser Ser Ile Glu Ser Thr Asn Glu Ala Val Val Lys Leu Gln Glu Thr

145 150 155 160

Ala Glu Lys Thr Val Tyr Val Leu Thr Ala Leu Gln Asp Tyr Ile Asn

165 170 175

Thr Asn Leu Val Pro Thr Ile Asp Lys Ile Ser Cys Lys Gln Thr Glu

180 185 190

Leu Ser Leu Asp Leu Ala Leu Ser Lys Tyr Leu Ser Asp Leu Leu Phe

195 200 205

Val Phe Gly Pro Asn Leu Gln Asp Pro Val Ser Asn Ser Met Thr Ile

210 215 220

Gln Ala Ile Ser Gln Ala Phe Gly Gly Asn Tyr Glu Thr Leu Leu Arg

225 230 235 240

Thr Leu Gly Tyr Ala Thr Glu Asp Phe Asp Asp Leu Leu Glu Ser Asp

245 250 255

Ser Ile Thr Gly Gln Ile Ile Tyr Val Asp Leu Ser Ser Tyr Tyr Ile

260 265 270

Ile Val Arg Val Tyr Phe Pro Ile Leu Thr Glu Ile Gln Gln Ala Tyr

275 280 285

Ile Gln Glu Leu Leu Pro Val Ser Phe Asn Asn Asp Asn Ser Glu Trp

290 295 300

Ile Ser Ile Val Pro Asn Phe Ile Leu Val Arg Asn Thr Leu Ile Ser

305 310 315 320

Asn Ile Glu Ile Gly Phe Cys Leu Ile Thr Lys Arg Ser Val Ile Cys

325 330 335

Asn Gln Asp Tyr Ala Thr Pro Met Thr Asn Asn Met Arg Glu Cys Leu

340 345 350

Thr Gly Ser Thr Glu Lys Cys Pro Arg Glu Leu Val Val Ser Ser His

355 360 365

Val Pro Arg Phe Ala Leu Ser Asn Gly Val Leu Phe Ala Asn Cys Ile

370 375 380

Ser Val Thr Cys Gln Cys Gln Thr Thr Gly Arg Ala Ile Ser Gln Ser

385 390 395 400

Gly Glu Gln Thr Leu Leu Met Ile Asp Asn Thr Thr Cys Pro Thr Ala

405 410 415

Val Leu Gly Asn Val Ile Ile Ser Leu Gly Lys Tyr Leu Gly Ser Val

420 425 430

Asn Tyr Asn Ser Glu Gly Ile Ala Ile Gly Pro Pro Val Phe Thr Asp

435 440 445

Lys Val Asp Ile Ser Ser Gln Ile Ser Ser Met Asn Gln Ser Leu Gln

450 455 460

Gln Ser Lys Asp Tyr Ile Lys Glu Ala Gln Arg Leu Leu Asp Thr Val

465 470 475 480

Asn Pro Ser Leu Lys Leu Met Lys Gln Ile Glu Asp Lys Ile Glu Glu

485 490 495

Ile Leu Ser Lys Ile Tyr His Ile Glu Asn Glu Ile Ala Arg Ile Lys

500 505 510

Lys Leu Ile Gly Glu Ala Pro Gly Gly Leu Val Pro Arg Gly Ser His

515 520 525

His His His His His Ser Ala Trp Ser His Pro Gln Phe Glu Lys

530 535 540

<210> 31

<211> 543

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 31

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Gly Ile Leu His Tyr Glu Lys Leu Ser Lys Ile

20 25 30

Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro

35 40 45

Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn Val Ser Asn Met

50 55 60

Ser Gln Cys Thr Gly Ser Val Met Glu Asn Tyr Lys Thr Arg Leu Asn

65 70 75 80

Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile Tyr Lys Asn Asn

85 90 95

Thr His Asp Cys Val Gly Asp Val Arg Leu Ala Gly Val Cys Met Ala

100 105 110

Gly Val Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile Thr Ala Gly Val

115 120 125

Ala Leu Tyr Glu Ala Met Lys Asn Ala Asp Asn Ile Asn Lys Leu Lys

130 135 140

Ser Ser Ile Glu Ser Thr Asn Glu Ala Val Val Lys Leu Cys Glu Thr

145 150 155 160

Ala Glu Lys Cys Val Tyr Val Phe Thr Ala Leu Gln Asp Tyr Ile Asn

165 170 175

Thr Asn Leu Val Pro Thr Ile Asp Lys Ile Pro Cys Lys Gln Thr Glu

180 185 190

Leu Ser Leu Asp Leu Ala Leu Ser Lys Tyr Leu Ser Asp Leu Leu Phe

195 200 205

Val Phe Gly Pro Asn Leu Gln Asp Pro Val Ser Asn Ser Met Thr Ile

210 215 220

Gln Ala Ile Ser Gln Ala Phe Gly Gly Asn Tyr Glu Thr Leu Leu Arg

225 230 235 240

Thr Leu Gly Tyr Ala Thr Glu Asp Phe Asp Asp Leu Leu Glu Ser Asp

245 250 255

Ser Ile Thr Gly Gln Ile Ile Tyr Val Asp Leu Ser Ser Tyr Tyr Ile

260 265 270

Ile Val Arg Val Tyr Phe Pro Ile Leu Thr Glu Ile Gln Gln Ala Tyr

275 280 285

Ile Gln Glu Leu Leu Pro Val Ser Phe Asn Asn Asp Asn Ser Glu Trp

290 295 300

Ile Ser Ile Val Pro Asn Phe Ile Leu Val Arg Asn Thr Leu Ile Ser

305 310 315 320

Asn Ile Glu Ile Gly Phe Cys Leu Ile Thr Lys Arg Ser Val Ile Cys

325 330 335

Asn Gln Asp Tyr Ala Thr Pro Met Thr Asn Asn Met Arg Glu Cys Leu

340 345 350

Thr Gly Ser Thr Glu Lys Cys Pro Arg Glu Leu Val Val Ser Ser His

355 360 365

Val Pro Arg Phe Ala Leu Ser Asn Gly Val Leu Phe Ala Asn Cys Ile

370 375 380

Ser Val Thr Cys Gln Cys Gln Thr Thr Gly Arg Ala Ile Ser Gln Ser

385 390 395 400

Gly Glu Gln Thr Leu Leu Met Ile Asp Asn Thr Thr Cys Pro Thr Ala

405 410 415

Val Leu Gly Asn Val Ile Ile Ser Leu Gly Lys Tyr Leu Gly Ser Val

420 425 430

Asn Tyr Asn Ser Glu Gly Ile Ala Ile Gly Pro Pro Val Phe Thr Asp

435 440 445

Lys Val Asp Ile Ser Ser Gln Ile Ser Ser Met Asn Gln Ser Leu Gln

450 455 460

Gln Ser Lys Asp Tyr Ile Lys Glu Ala Gln Arg Leu Leu Asp Thr Val

465 470 475 480

Asn Pro Ser Leu Lys Leu Met Lys Gln Ile Glu Asp Lys Ile Glu Glu

485 490 495

Ile Leu Ser Lys Ile Tyr His Ile Glu Asn Glu Ile Ala Arg Ile Lys

500 505 510

Lys Leu Ile Gly Glu Ala Pro Gly Gly Leu Val Pro Arg Gly Ser His

515 520 525

His His His His His Ser Ala Trp Ser His Pro Gln Phe Glu Lys

530 535 540

<210> 32

<211> 543

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 32

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Gly Ile Leu His Tyr Glu Lys Leu Ser Lys Ile

20 25 30

Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro

35 40 45

Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn Val Ser Asn Met

50 55 60

Ser Gln Cys Thr Gly Ser Val Met Glu Asn Tyr Lys Thr Arg Leu Asn

65 70 75 80

Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile Tyr Lys Asn Asn

85 90 95

Thr His Asp Cys Val Gly Asp Val Arg Leu Ala Gly Val Cys Met Ala

100 105 110

Gly Val Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile Thr Cys Gly Val

115 120 125

Ala Leu Tyr Glu Ala Met Lys Asn Ala Asp Asn Ile Asn Lys Leu Lys

130 135 140

Ser Ser Ile Glu Ser Thr Asn Glu Ala Val Val Lys Leu Gln Glu Thr

145 150 155 160

Ala Glu Lys Thr Val Tyr Val Phe Thr Ala Leu Gln Asp Tyr Ile Asn

165 170 175

Thr Asn Leu Val Pro Thr Ile Asp Lys Ile Pro Cys Lys Gln Thr Glu

180 185 190

Leu Ser Leu Asp Leu Ala Leu Ser Lys Tyr Leu Ser Asp Leu Leu Phe

195 200 205

Val Phe Gly Pro Asn Leu Gln Asp Pro Cys Ser Asn Ser Met Thr Ile

210 215 220

Gln Ala Ile Ser Gln Ala Phe Gly Gly Asn Tyr Glu Thr Leu Leu Arg

225 230 235 240

Thr Leu Gly Tyr Ala Thr Glu Asp Phe Asp Asp Leu Leu Glu Ser Asp

245 250 255

Ser Ile Thr Gly Gln Ile Ile Tyr Val Asp Leu Ser Ser Tyr Tyr Ile

260 265 270

Ile Val Arg Val Tyr Phe Pro Ile Leu Thr Glu Ile Gln Gln Ala Tyr

275 280 285

Ile Gln Glu Leu Leu Pro Val Ser Phe Asn Asn Asp Asn Ser Glu Trp

290 295 300

Ile Ser Ile Val Pro Asn Phe Ile Leu Val Arg Asn Thr Leu Ile Ser

305 310 315 320

Asn Ile Glu Ile Gly Phe Cys Leu Ile Thr Lys Arg Ser Val Ile Cys

325 330 335

Asn Gln Asp Tyr Ala Thr Pro Met Thr Asn Asn Met Arg Glu Cys Leu

340 345 350

Thr Gly Ser Thr Glu Lys Cys Pro Arg Glu Leu Val Val Ser Ser His

355 360 365

Val Pro Arg Phe Ala Leu Ser Asn Gly Val Leu Phe Ala Asn Cys Ile

370 375 380

Ser Val Thr Cys Gln Cys Gln Thr Thr Gly Arg Ala Ile Ser Gln Ser

385 390 395 400

Gly Glu Gln Thr Leu Leu Met Ile Asp Asn Thr Thr Cys Pro Thr Ala

405 410 415

Val Leu Gly Asn Val Ile Ile Ser Leu Gly Lys Tyr Leu Gly Ser Val

420 425 430

Asn Tyr Asn Ser Glu Gly Ile Ala Ile Gly Pro Pro Val Phe Thr Asp

435 440 445

Lys Val Asp Ile Ser Ser Gln Ile Ser Ser Met Asn Gln Ser Leu Gln

450 455 460

Gln Ser Lys Asp Tyr Ile Lys Glu Ala Gln Arg Leu Leu Asp Thr Val

465 470 475 480

Asn Pro Ser Leu Lys Leu Met Lys Gln Ile Glu Asp Lys Ile Glu Glu

485 490 495

Ile Leu Ser Lys Ile Tyr His Ile Glu Asn Glu Ile Ala Arg Ile Lys

500 505 510

Lys Leu Ile Gly Glu Ala Pro Gly Gly Leu Val Pro Arg Gly Ser His

515 520 525

His His His His His Ser Ala Trp Ser His Pro Gln Phe Glu Lys

530 535 540

<210> 33

<211> 1662

<212> DNA

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 33

tctagagcca ccatggtggt catcctggac aagagatgct actgtaacct gctgatcctg 60

atcctgatga tcagcgagtg ctccgtgggc atcctgcact acgagaagct gtccaagatc 120

ggcctggtga agggcgtgac caggaagtat aagatcaagt ctaatcccct gacaaaggat 180

atcgtgatca agatgatccc taacgtgtct aatatgagcc agtgtaccgg ctccgtgatg 240

gagaactaca agaccagact gaatggcatc ctgacaccca tcaagggcgc cctggagatc 300

tataagaaca atacacacga ctgcgtgggc gatgtgaggc tggcaggcgt gtgcatggca 360

ggagtggcaa tcggaatcgc aaccgcagca cagatcacag caggagtggc cctgtatgag 420

gccatgaaga acgccgacaa catcaataag ctgaagagct ccatcgagag caccaatgag 480

gccgtggtga agctgcagga gaccgccgag aagacagtgt acgtgttcac agccctgcag 540

gactatatca acaccaatct ggtgcctaca atcgataaga tcccttgcaa gcagaccgag 600

ctgagcctgg acctggccct gagcaagtac ctgtccgatc tgctgttcgt gtttggccca 660

aacctgcagg accccgtgag caattccatg acaatccagg ccatctccca ggccttcggc 720

ggcaactacg agaccctgct gcgcacactg ggctatgcca ccgaggactt tgacgatctg 780

ctggagtctg atagcatcac aggccagatc atctatgtgg acctgtctag ctactatatc 840

atcgtgcggg tgtacttccc aatcctgacc gagatccagc aggcctatat ccaggagctg 900

ctgcccgtgt ccttcaacaa tgataactct gagtggatca gcatcgtgcc taacttcatc 960

ctggtgcgga acaccctgat ctctaatatc gagatcggct tttgcctgat cacaaagcgc 1020

agcgtgatct gtaatcagga ctacgccacc cctatgacaa acaatatgcg ggagtgcctg 1080

accggcagca cagagaagtg tcctcgggag ctggtggtgt cctctcacgt gccaagattc 1140

gccctgtcca acggcgtgct gtttgccaat tgcatctctg tgacctgcca gtgtcagacc 1200

acaggcaggg ccatctccca gtctggcgag cagaccctgc tgatgatcga taacaccaca 1260

tgtccaacag ccgtgctggg caatgtgatc atcagcctgg gcaagtacct gggcagcgtg 1320

aactataatt ccgagggaat cgcaatcgga ccacccgtgt tcaccgacaa ggtggatatc 1380

agctcccaga tctctagcat gaaccagtcc ctgcagcagt ctaaggacta catcaaggag 1440

gcccagcgcc tgctggatac cgtgaatcca tccctgatct ctatgctgag catgatcatc 1500

ctgtatgtgc tgtccatcgc ctctctgtgc atcggcctga tcaccttcat cagctttatc 1560

atcgtggaga agaagaggaa cacatactcc cgcctggagg acaggagagt gcggcccacc 1620

tcctctggcg atctgtacta tatcggcaca tgatgaggat cc 1662

<210> 34

<211> 507

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒G序列

<400> 34

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Gly Ser Gly Tyr Ile Pro Glu Ala Pro Arg Asp

20 25 30

Gly Gln Ala Tyr Val Arg Lys Asp Gly Glu Trp Val Leu Leu Ser Thr

35 40 45

Phe Leu Gly Ser Gly Gly Gly Gly Gly Gly Val Ser Asn Leu Val Gly

50 55 60

Leu Pro Asn Asn Ile Cys Leu Gln Lys Thr Ser Asn Gln Ile Leu Lys

65 70 75 80

Pro Lys Leu Ile Ser Tyr Thr Leu Pro Val Val Gly Gln Ser Gly Thr

85 90 95

Cys Ile Thr Asp Pro Leu Leu Ala Met Asp Glu Gly Tyr Phe Ala Tyr

100 105 110

Ser His Leu Glu Arg Ile Gly Ser Cys Ser Arg Gly Val Ser Lys Gln

115 120 125

Arg Ile Ile Gly Val Gly Glu Val Leu Asp Arg Gly Asp Glu Val Pro

130 135 140

Ser Leu Phe Met Thr Asn Val Trp Thr Pro Pro Asn Pro Asn Thr Val

145 150 155 160

Tyr His Cys Ser Ala Val Tyr Asn Asn Glu Phe Tyr Tyr Val Leu Cys

165 170 175

Ala Val Ser Thr Val Gly Asp Pro Ile Leu Asn Ser Thr Tyr Trp Ser

180 185 190

Gly Ser Leu Met Met Thr Arg Leu Ala Val Lys Pro Lys Ser Asn Gly

195 200 205

Gly Gly Tyr Asn Gln His Gln Leu Ala Leu Arg Ser Ile Glu Lys Gly

210 215 220

Arg Tyr Asp Lys Val Met Pro Tyr Gly Pro Ser Gly Ile Lys Gln Gly

225 230 235 240

Asp Thr Leu Tyr Phe Pro Ala Val Gly Phe Leu Val Arg Thr Glu Phe

245 250 255

Lys Tyr Asn Asp Ser Asn Cys Pro Ile Thr Lys Cys Gln Tyr Ser Lys

260 265 270

Pro Glu Asn Cys Arg Leu Ser Met Gly Ile Arg Pro Asn Ser His Tyr

275 280 285

Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn Leu Ser Asp Gly Glu Asn

290 295 300

Pro Lys Val Val Phe Ile Glu Ile Ser Asp Gln Arg Leu Ser Ile Gly

305 310 315 320

Ser Pro Ser Lys Ile Tyr Asp Ser Leu Gly Gln Pro Val Phe Tyr Gln

325 330 335

Ala Ser Phe Ser Trp Asp Thr Met Ile Lys Phe Gly Asp Val Leu Thr

340 345 350

Val Asn Pro Leu Val Val Asn Trp Arg Asn Asn Thr Val Ile Ser Arg

355 360 365

Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn Thr Cys Pro Glu Ile Cys

370 375 380

Trp Glu Gly Val Tyr Asn Asp Ala Phe Leu Ile Asp Arg Ile Asn Trp

385 390 395 400

Ile Ser Ala Gly Val Phe Leu Asp Ser Asn Gln Thr Ala Glu Asn Pro

405 410 415

Val Phe Thr Val Phe Lys Asp Asn Glu Ile Leu Tyr Arg Ala Gln Leu

420 425 430

Ala Ser Glu Asp Thr Asn Ala Gln Lys Thr Ile Thr Asn Cys Phe Leu

435 440 445

Leu Lys Asn Lys Ile Trp Cys Ile Ser Leu Val Glu Ile Tyr Asp Thr

450 455 460

Gly Asp Asn Val Ile Arg Pro Lys Leu Phe Ala Val Lys Ile Pro Glu

465 470 475 480

Gln Cys Thr Gly Gly Leu Val Pro Arg Gly Ser His His His His His

485 490 495

His Ser Ala Trp Ser His Pro Gln Phe Glu Lys

500 505

<210> 35

<211> 939

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒G序列

<400> 35

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Gly Ser Gly Tyr Ile Pro Glu Ala Pro Arg Asp

20 25 30

Gly Gln Ala Tyr Val Arg Lys Asp Gly Glu Trp Val Leu Leu Ser Thr

35 40 45

Phe Leu Gly Ser Gly Gly Gly Gly Gly Gly Val Ser Asn Leu Val Gly

50 55 60

Leu Pro Asn Asn Ile Cys Leu Gln Lys Thr Ser Asn Gln Ile Leu Lys

65 70 75 80

Pro Lys Leu Ile Ser Tyr Thr Leu Pro Val Val Gly Gln Ser Gly Thr

85 90 95

Cys Ile Thr Asp Pro Leu Leu Ala Met Asp Glu Gly Tyr Phe Ala Tyr

100 105 110

Ser His Leu Glu Arg Ile Gly Ser Cys Ser Arg Gly Val Ser Lys Gln

115 120 125

Arg Ile Ile Gly Val Gly Glu Val Leu Asp Arg Gly Asp Glu Val Pro

130 135 140

Ser Leu Phe Met Thr Asn Val Trp Thr Pro Pro Asn Pro Asn Thr Val

145 150 155 160

Tyr His Cys Ser Ala Val Tyr Asn Asn Glu Phe Tyr Tyr Val Leu Cys

165 170 175

Ala Val Ser Thr Val Gly Asp Pro Ile Leu Asn Ser Thr Tyr Trp Ser

180 185 190

Gly Ser Leu Met Met Thr Arg Leu Ala Val Lys Pro Lys Ser Asn Gly

195 200 205

Gly Gly Tyr Asn Gln His Gln Leu Ala Leu Arg Ser Ile Glu Lys Gly

210 215 220

Arg Tyr Asp Lys Val Met Pro Tyr Gly Pro Ser Gly Ile Lys Gln Gly

225 230 235 240

Asp Thr Leu Tyr Phe Pro Ala Val Gly Phe Leu Val Arg Thr Glu Phe

245 250 255

Lys Tyr Asn Asp Ser Asn Cys Pro Ile Thr Lys Cys Gln Tyr Ser Lys

260 265 270

Pro Glu Asn Cys Arg Leu Ser Met Gly Ile Arg Pro Asn Ser His Tyr

275 280 285

Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn Leu Ser Asp Gly Glu Asn

290 295 300

Pro Lys Val Val Phe Ile Glu Ile Ser Asp Gln Arg Leu Ser Ile Gly

305 310 315 320

Ser Pro Ser Lys Ile Tyr Asp Ser Leu Gly Gln Pro Val Phe Tyr Gln

325 330 335

Ala Ser Phe Ser Trp Asp Thr Met Ile Lys Phe Gly Asp Val Leu Thr

340 345 350

Val Asn Pro Leu Val Val Asn Trp Arg Asn Asn Thr Val Ile Ser Arg

355 360 365

Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn Thr Cys Pro Glu Ile Cys

370 375 380

Trp Glu Gly Val Tyr Asn Asp Ala Phe Leu Ile Asp Arg Ile Asn Trp

385 390 395 400

Ile Ser Ala Gly Val Phe Leu Asp Ser Asn Gln Thr Ala Glu Asn Pro

405 410 415

Val Phe Thr Val Phe Lys Asp Asn Glu Ile Leu Tyr Arg Ala Gln Leu

420 425 430

Ala Ser Glu Asp Thr Asn Ala Gln Lys Thr Ile Thr Asn Cys Phe Leu

435 440 445

Leu Lys Asn Lys Ile Trp Cys Ile Ser Leu Val Glu Ile Tyr Asp Thr

450 455 460

Gly Asp Asn Val Ile Arg Pro Lys Leu Phe Ala Val Lys Ile Pro Glu

465 470 475 480

Gln Cys Thr Gly Gly Gly Gly Gly Gly Gly Val Ser Asn Leu Val Gly

485 490 495

Leu Pro Asn Asn Ile Cys Leu Gln Lys Thr Ser Asn Gln Ile Leu Lys

500 505 510

Pro Lys Leu Ile Ser Tyr Thr Leu Pro Val Val Gly Gln Ser Gly Thr

515 520 525

Cys Ile Thr Asp Pro Leu Leu Ala Met Asp Glu Gly Tyr Phe Ala Tyr

530 535 540

Ser His Leu Glu Arg Ile Gly Ser Cys Ser Arg Gly Val Ser Lys Gln

545 550 555 560

Arg Ile Ile Gly Val Gly Glu Val Leu Asp Arg Gly Asp Glu Val Pro

565 570 575

Ser Leu Phe Met Thr Asn Val Trp Thr Pro Pro Asn Pro Asn Thr Val

580 585 590

Tyr His Cys Ser Ala Val Tyr Asn Asn Glu Phe Tyr Tyr Val Leu Cys

595 600 605

Ala Val Ser Thr Val Gly Asp Pro Ile Leu Asn Ser Thr Tyr Trp Ser

610 615 620

Gly Ser Leu Met Met Thr Arg Leu Ala Val Lys Pro Lys Ser Asn Gly

625 630 635 640

Gly Gly Tyr Asn Gln His Gln Leu Ala Leu Arg Ser Ile Glu Lys Gly

645 650 655

Arg Tyr Asp Lys Val Met Pro Tyr Gly Pro Ser Gly Ile Lys Gln Gly

660 665 670

Asp Thr Leu Tyr Phe Pro Ala Val Gly Phe Leu Val Arg Thr Glu Phe

675 680 685

Lys Tyr Asn Asp Ser Asn Cys Pro Ile Thr Lys Cys Gln Tyr Ser Lys

690 695 700

Pro Glu Asn Cys Arg Leu Ser Met Gly Ile Arg Pro Asn Ser His Tyr

705 710 715 720

Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn Leu Ser Asp Gly Glu Asn

725 730 735

Pro Lys Val Val Phe Ile Glu Ile Ser Asp Gln Arg Leu Ser Ile Gly

740 745 750

Ser Pro Ser Lys Ile Tyr Asp Ser Leu Gly Gln Pro Val Phe Tyr Gln

755 760 765

Ala Ser Phe Ser Trp Asp Thr Met Ile Lys Phe Gly Asp Val Leu Thr

770 775 780

Val Asn Pro Leu Val Val Asn Trp Arg Asn Asn Thr Val Ile Ser Arg

785 790 795 800

Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn Thr Cys Pro Glu Ile Cys

805 810 815

Trp Glu Gly Val Tyr Asn Asp Ala Phe Leu Ile Asp Arg Ile Asn Trp

820 825 830

Ile Ser Ala Gly Val Phe Leu Asp Ser Asn Gln Thr Ala Glu Asn Pro

835 840 845

Val Phe Thr Val Phe Lys Asp Asn Glu Ile Leu Tyr Arg Ala Gln Leu

850 855 860

Ala Ser Glu Asp Thr Asn Ala Gln Lys Thr Ile Thr Asn Cys Phe Leu

865 870 875 880

Leu Lys Asn Lys Ile Trp Cys Ile Ser Leu Val Glu Ile Tyr Asp Thr

885 890 895

Gly Asp Asn Val Ile Arg Pro Lys Leu Phe Ala Val Lys Ile Pro Glu

900 905 910

Gln Cys Thr Gly Gly Leu Val Pro Arg Gly Ser His His His His His

915 920 925

His Ser Ala Trp Ser His Pro Gln Phe Glu Lys

930 935

<210> 36

<211> 1371

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒G序列

<400> 36

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Gly Ser Gly Tyr Ile Pro Glu Ala Pro Arg Asp

20 25 30

Gly Gln Ala Tyr Val Arg Lys Asp Gly Glu Trp Val Leu Leu Ser Thr

35 40 45

Phe Leu Gly Ser Gly Gly Gly Gly Gly Gly Val Ser Asn Leu Val Gly

50 55 60

Leu Pro Asn Asn Ile Cys Leu Gln Lys Thr Ser Asn Gln Ile Leu Lys

65 70 75 80

Pro Lys Leu Ile Ser Tyr Thr Leu Pro Val Val Gly Gln Ser Gly Thr

85 90 95

Cys Ile Thr Asp Pro Leu Leu Ala Met Asp Glu Gly Tyr Phe Ala Tyr

100 105 110

Ser His Leu Glu Arg Ile Gly Ser Cys Ser Arg Gly Val Ser Lys Gln

115 120 125

Arg Ile Ile Gly Val Gly Glu Val Leu Asp Arg Gly Asp Glu Val Pro

130 135 140

Ser Leu Phe Met Thr Asn Val Trp Thr Pro Pro Asn Pro Asn Thr Val

145 150 155 160

Tyr His Cys Ser Ala Val Tyr Asn Asn Glu Phe Tyr Tyr Val Leu Cys

165 170 175

Ala Val Ser Thr Val Gly Asp Pro Ile Leu Asn Ser Thr Tyr Trp Ser

180 185 190

Gly Ser Leu Met Met Thr Arg Leu Ala Val Lys Pro Lys Ser Asn Gly

195 200 205

Gly Gly Tyr Asn Gln His Gln Leu Ala Leu Arg Ser Ile Glu Lys Gly

210 215 220

Arg Tyr Asp Lys Val Met Pro Tyr Gly Pro Ser Gly Ile Lys Gln Gly

225 230 235 240

Asp Thr Leu Tyr Phe Pro Ala Val Gly Phe Leu Val Arg Thr Glu Phe

245 250 255

Lys Tyr Asn Asp Ser Asn Cys Pro Ile Thr Lys Cys Gln Tyr Ser Lys

260 265 270

Pro Glu Asn Cys Arg Leu Ser Met Gly Ile Arg Pro Asn Ser His Tyr

275 280 285

Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn Leu Ser Asp Gly Glu Asn

290 295 300

Pro Lys Val Val Phe Ile Glu Ile Ser Asp Gln Arg Leu Ser Ile Gly

305 310 315 320

Ser Pro Ser Lys Ile Tyr Asp Ser Leu Gly Gln Pro Val Phe Tyr Gln

325 330 335

Ala Ser Phe Ser Trp Asp Thr Met Ile Lys Phe Gly Asp Val Leu Thr

340 345 350

Val Asn Pro Leu Val Val Asn Trp Arg Asn Asn Thr Val Ile Ser Arg

355 360 365

Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn Thr Cys Pro Glu Ile Cys

370 375 380

Trp Glu Gly Val Tyr Asn Asp Ala Phe Leu Ile Asp Arg Ile Asn Trp

385 390 395 400

Ile Ser Ala Gly Val Phe Leu Asp Ser Asn Gln Thr Ala Glu Asn Pro

405 410 415

Val Phe Thr Val Phe Lys Asp Asn Glu Ile Leu Tyr Arg Ala Gln Leu

420 425 430

Ala Ser Glu Asp Thr Asn Ala Gln Lys Thr Ile Thr Asn Cys Phe Leu

435 440 445

Leu Lys Asn Lys Ile Trp Cys Ile Ser Leu Val Glu Ile Tyr Asp Thr

450 455 460

Gly Asp Asn Val Ile Arg Pro Lys Leu Phe Ala Val Lys Ile Pro Glu

465 470 475 480

Gln Cys Thr Gly Gly Gly Gly Gly Gly Gly Val Ser Asn Leu Val Gly

485 490 495

Leu Pro Asn Asn Ile Cys Leu Gln Lys Thr Ser Asn Gln Ile Leu Lys

500 505 510

Pro Lys Leu Ile Ser Tyr Thr Leu Pro Val Val Gly Gln Ser Gly Thr

515 520 525

Cys Ile Thr Asp Pro Leu Leu Ala Met Asp Glu Gly Tyr Phe Ala Tyr

530 535 540

Ser His Leu Glu Arg Ile Gly Ser Cys Ser Arg Gly Val Ser Lys Gln

545 550 555 560

Arg Ile Ile Gly Val Gly Glu Val Leu Asp Arg Gly Asp Glu Val Pro

565 570 575

Ser Leu Phe Met Thr Asn Val Trp Thr Pro Pro Asn Pro Asn Thr Val

580 585 590

Tyr His Cys Ser Ala Val Tyr Asn Asn Glu Phe Tyr Tyr Val Leu Cys

595 600 605

Ala Val Ser Thr Val Gly Asp Pro Ile Leu Asn Ser Thr Tyr Trp Ser

610 615 620

Gly Ser Leu Met Met Thr Arg Leu Ala Val Lys Pro Lys Ser Asn Gly

625 630 635 640

Gly Gly Tyr Asn Gln His Gln Leu Ala Leu Arg Ser Ile Glu Lys Gly

645 650 655

Arg Tyr Asp Lys Val Met Pro Tyr Gly Pro Ser Gly Ile Lys Gln Gly

660 665 670

Asp Thr Leu Tyr Phe Pro Ala Val Gly Phe Leu Val Arg Thr Glu Phe

675 680 685

Lys Tyr Asn Asp Ser Asn Cys Pro Ile Thr Lys Cys Gln Tyr Ser Lys

690 695 700

Pro Glu Asn Cys Arg Leu Ser Met Gly Ile Arg Pro Asn Ser His Tyr

705 710 715 720

Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn Leu Ser Asp Gly Glu Asn

725 730 735

Pro Lys Val Val Phe Ile Glu Ile Ser Asp Gln Arg Leu Ser Ile Gly

740 745 750

Ser Pro Ser Lys Ile Tyr Asp Ser Leu Gly Gln Pro Val Phe Tyr Gln

755 760 765

Ala Ser Phe Ser Trp Asp Thr Met Ile Lys Phe Gly Asp Val Leu Thr

770 775 780

Val Asn Pro Leu Val Val Asn Trp Arg Asn Asn Thr Val Ile Ser Arg

785 790 795 800

Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn Thr Cys Pro Glu Ile Cys

805 810 815

Trp Glu Gly Val Tyr Asn Asp Ala Phe Leu Ile Asp Arg Ile Asn Trp

820 825 830

Ile Ser Ala Gly Val Phe Leu Asp Ser Asn Gln Thr Ala Glu Asn Pro

835 840 845

Val Phe Thr Val Phe Lys Asp Asn Glu Ile Leu Tyr Arg Ala Gln Leu

850 855 860

Ala Ser Glu Asp Thr Asn Ala Gln Lys Thr Ile Thr Asn Cys Phe Leu

865 870 875 880

Leu Lys Asn Lys Ile Trp Cys Ile Ser Leu Val Glu Ile Tyr Asp Thr

885 890 895

Gly Asp Asn Val Ile Arg Pro Lys Leu Phe Ala Val Lys Ile Pro Glu

900 905 910

Gln Cys Thr Gly Gly Gly Gly Gly Gly Gly Val Ser Asn Leu Val Gly

915 920 925

Leu Pro Asn Asn Ile Cys Leu Gln Lys Thr Ser Asn Gln Ile Leu Lys

930 935 940

Pro Lys Leu Ile Ser Tyr Thr Leu Pro Val Val Gly Gln Ser Gly Thr

945 950 955 960

Cys Ile Thr Asp Pro Leu Leu Ala Met Asp Glu Gly Tyr Phe Ala Tyr

965 970 975

Ser His Leu Glu Arg Ile Gly Ser Cys Ser Arg Gly Val Ser Lys Gln

980 985 990

Arg Ile Ile Gly Val Gly Glu Val Leu Asp Arg Gly Asp Glu Val Pro

995 1000 1005

Ser Leu Phe Met Thr Asn Val Trp Thr Pro Pro Asn Pro Asn Thr

1010 1015 1020

Val Tyr His Cys Ser Ala Val Tyr Asn Asn Glu Phe Tyr Tyr Val

1025 1030 1035

Leu Cys Ala Val Ser Thr Val Gly Asp Pro Ile Leu Asn Ser Thr

1040 1045 1050

Tyr Trp Ser Gly Ser Leu Met Met Thr Arg Leu Ala Val Lys Pro

1055 1060 1065

Lys Ser Asn Gly Gly Gly Tyr Asn Gln His Gln Leu Ala Leu Arg

1070 1075 1080

Ser Ile Glu Lys Gly Arg Tyr Asp Lys Val Met Pro Tyr Gly Pro

1085 1090 1095

Ser Gly Ile Lys Gln Gly Asp Thr Leu Tyr Phe Pro Ala Val Gly

1100 1105 1110

Phe Leu Val Arg Thr Glu Phe Lys Tyr Asn Asp Ser Asn Cys Pro

1115 1120 1125

Ile Thr Lys Cys Gln Tyr Ser Lys Pro Glu Asn Cys Arg Leu Ser

1130 1135 1140

Met Gly Ile Arg Pro Asn Ser His Tyr Ile Leu Arg Ser Gly Leu

1145 1150 1155

Leu Lys Tyr Asn Leu Ser Asp Gly Glu Asn Pro Lys Val Val Phe

1160 1165 1170

Ile Glu Ile Ser Asp Gln Arg Leu Ser Ile Gly Ser Pro Ser Lys

1175 1180 1185

Ile Tyr Asp Ser Leu Gly Gln Pro Val Phe Tyr Gln Ala Ser Phe

1190 1195 1200

Ser Trp Asp Thr Met Ile Lys Phe Gly Asp Val Leu Thr Val Asn

1205 1210 1215

Pro Leu Val Val Asn Trp Arg Asn Asn Thr Val Ile Ser Arg Pro

1220 1225 1230

Gly Gln Ser Gln Cys Pro Arg Phe Asn Thr Cys Pro Glu Ile Cys

1235 1240 1245

Trp Glu Gly Val Tyr Asn Asp Ala Phe Leu Ile Asp Arg Ile Asn

1250 1255 1260

Trp Ile Ser Ala Gly Val Phe Leu Asp Ser Asn Gln Thr Ala Glu

1265 1270 1275

Asn Pro Val Phe Thr Val Phe Lys Asp Asn Glu Ile Leu Tyr Arg

1280 1285 1290

Ala Gln Leu Ala Ser Glu Asp Thr Asn Ala Gln Lys Thr Ile Thr

1295 1300 1305

Asn Cys Phe Leu Leu Lys Asn Lys Ile Trp Cys Ile Ser Leu Val

1310 1315 1320

Glu Ile Tyr Asp Thr Gly Asp Asn Val Ile Arg Pro Lys Leu Phe

1325 1330 1335

Ala Val Lys Ile Pro Glu Gln Cys Thr Gly Gly Leu Val Pro Arg

1340 1345 1350

Gly Ser His His His His His His Ser Ala Trp Ser His Pro Gln

1355 1360 1365

Phe Glu Lys

1370

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<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒G序列

<400> 37

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Glu Gly Val Ser Asn Leu Val Gly Leu Pro Asn

20 25 30

Asn Ile Cys Leu Gln Lys Thr Ser Asn Gln Ile Leu Lys Pro Lys Leu

35 40 45

Ile Ser Tyr Thr Leu Pro Val Val Gly Gln Ser Gly Thr Cys Ile Thr

50 55 60

Asp Pro Leu Leu Ala Met Asp Glu Gly Tyr Phe Ala Tyr Ser His Leu

65 70 75 80

Glu Arg Ile Gly Ser Cys Ser Arg Gly Val Ser Lys Gln Arg Ile Ile

85 90 95

Gly Val Gly Glu Val Leu Asp Arg Gly Asp Glu Val Pro Ser Leu Phe

100 105 110

Met Thr Asn Val Trp Thr Pro Pro Asn Pro Asn Thr Val Tyr His Cys

115 120 125

Ser Ala Val Tyr Asn Asn Glu Phe Tyr Tyr Val Leu Cys Ala Val Ser

130 135 140

Thr Val Gly Asp Pro Ile Leu Asn Ser Thr Tyr Trp Ser Gly Ser Leu

145 150 155 160

Met Met Thr Arg Leu Ala Val Lys Pro Lys Ser Asn Gly Gly Gly Tyr

165 170 175

Asn Gln His Gln Leu Ala Leu Arg Ser Ile Glu Lys Gly Arg Tyr Asp

180 185 190

Lys Val Met Pro Tyr Gly Pro Ser Gly Ile Lys Gln Gly Asp Thr Leu

195 200 205

Tyr Phe Pro Ala Val Gly Phe Leu Val Arg Thr Glu Phe Lys Tyr Asn

210 215 220

Asp Ser Asn Cys Pro Ile Thr Lys Cys Gln Tyr Ser Lys Pro Glu Asn

225 230 235 240

Cys Arg Leu Ser Met Gly Ile Arg Pro Asn Ser His Tyr Ile Leu Arg

245 250 255

Ser Gly Leu Leu Lys Tyr Asn Leu Ser Asp Gly Glu Asn Pro Lys Val

260 265 270

Val Phe Ile Glu Ile Ser Asp Gln Arg Leu Ser Ile Gly Ser Pro Ser

275 280 285

Lys Ile Tyr Asp Ser Leu Gly Gln Pro Val Phe Tyr Gln Ala Ser Phe

290 295 300

Ser Trp Asp Thr Met Ile Lys Phe Gly Asp Val Leu Thr Val Asn Pro

305 310 315 320

Leu Val Val Asn Trp Arg Asn Asn Thr Val Ile Ser Arg Pro Gly Gln

325 330 335

Ser Gln Cys Pro Arg Phe Asn Thr Cys Pro Glu Ile Cys Trp Glu Gly

340 345 350

Val Tyr Asn Asp Ala Phe Leu Ile Asp Arg Ile Asn Trp Ile Ser Ala

355 360 365

Gly Val Phe Leu Asp Ser Asn Gln Thr Ala Glu Asn Pro Val Phe Thr

370 375 380

Val Phe Lys Asp Asn Glu Ile Leu Tyr Arg Ala Gln Leu Ala Ser Glu

385 390 395 400

Asp Thr Asn Ala Gln Lys Thr Ile Thr Asn Cys Phe Leu Leu Lys Asn

405 410 415

Lys Ile Trp Cys Ile Ser Leu Val Glu Ile Tyr Asp Thr Gly Asp Asn

420 425 430

Val Ile Arg Pro Lys Leu Phe Ala Val Lys Ile Pro Glu Gln Cys Thr

435 440 445

Gly Gly Gly Ser Gly Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln Ala

450 455 460

Tyr Val Arg Lys Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu Gly

465 470 475 480

Ser Gly Gly Gly Gly Gly Gly Val Ser Asn Leu Val Gly Leu Pro Asn

485 490 495

Asn Ile Cys Leu Gln Lys Thr Ser Asn Gln Ile Leu Lys Pro Lys Leu

500 505 510

Ile Ser Tyr Thr Leu Pro Val Val Gly Gln Ser Gly Thr Cys Ile Thr

515 520 525

Asp Pro Leu Leu Ala Met Asp Glu Gly Tyr Phe Ala Tyr Ser His Leu

530 535 540

Glu Arg Ile Gly Ser Cys Ser Arg Gly Val Ser Lys Gln Arg Ile Ile

545 550 555 560

Gly Val Gly Glu Val Leu Asp Arg Gly Asp Glu Val Pro Ser Leu Phe

565 570 575

Met Thr Asn Val Trp Thr Pro Pro Asn Pro Asn Thr Val Tyr His Cys

580 585 590

Ser Ala Val Tyr Asn Asn Glu Phe Tyr Tyr Val Leu Cys Ala Val Ser

595 600 605

Thr Val Gly Asp Pro Ile Leu Asn Ser Thr Tyr Trp Ser Gly Ser Leu

610 615 620

Met Met Thr Arg Leu Ala Val Lys Pro Lys Ser Asn Gly Gly Gly Tyr

625 630 635 640

Asn Gln His Gln Leu Ala Leu Arg Ser Ile Glu Lys Gly Arg Tyr Asp

645 650 655

Lys Val Met Pro Tyr Gly Pro Ser Gly Ile Lys Gln Gly Asp Thr Leu

660 665 670

Tyr Phe Pro Ala Val Gly Phe Leu Val Arg Thr Glu Phe Lys Tyr Asn

675 680 685

Asp Ser Asn Cys Pro Ile Thr Lys Cys Gln Tyr Ser Lys Pro Glu Asn

690 695 700

Cys Arg Leu Ser Met Gly Ile Arg Pro Asn Ser His Tyr Ile Leu Arg

705 710 715 720

Ser Gly Leu Leu Lys Tyr Asn Leu Ser Asp Gly Glu Asn Pro Lys Val

725 730 735

Val Phe Ile Glu Ile Ser Asp Gln Arg Leu Ser Ile Gly Ser Pro Ser

740 745 750

Lys Ile Tyr Asp Ser Leu Gly Gln Pro Val Phe Tyr Gln Ala Ser Phe

755 760 765

Ser Trp Asp Thr Met Ile Lys Phe Gly Asp Val Leu Thr Val Asn Pro

770 775 780

Leu Val Val Asn Trp Arg Asn Asn Thr Val Ile Ser Arg Pro Gly Gln

785 790 795 800

Ser Gln Cys Pro Arg Phe Asn Thr Cys Pro Glu Ile Cys Trp Glu Gly

805 810 815

Val Tyr Asn Asp Ala Phe Leu Ile Asp Arg Ile Asn Trp Ile Ser Ala

820 825 830

Gly Val Phe Leu Asp Ser Asn Gln Thr Ala Glu Asn Pro Val Phe Thr

835 840 845

Val Phe Lys Asp Asn Glu Ile Leu Tyr Arg Ala Gln Leu Ala Ser Glu

850 855 860

Asp Thr Asn Ala Gln Lys Thr Ile Thr Asn Cys Phe Leu Leu Lys Asn

865 870 875 880

Lys Ile Trp Cys Ile Ser Leu Val Glu Ile Tyr Asp Thr Gly Asp Asn

885 890 895

Val Ile Arg Pro Lys Leu Phe Ala Val Lys Ile Pro Glu Gln Cys Thr

900 905 910

Gly Gly Leu Val Pro Arg Gly Ser His His His His His His Ser Ala

915 920 925

Trp Ser His Pro Gln Phe Glu Lys

930 935

<210> 38

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<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒G序列

<400> 38

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln His His His His His His Gly Ser Ala Trp Ser

20 25 30

His Pro Gln Phe Glu Lys Gly Gly Leu Val Pro Arg Gly Ser Gly Asn

35 40 45

Ser Gln Arg Pro Gln Thr Glu Gly Val Ser Asn Leu Val Gly Leu Pro

50 55 60

Asn Asn Ile Cys Leu Gln Lys Thr Ser Asn Gln Ile Leu Lys Pro Lys

65 70 75 80

Leu Ile Ser Tyr Thr Leu Pro Val Val Gly Gln Ser Gly Thr Cys Ile

85 90 95

Thr Asp Pro Leu Leu Ala Met Asp Glu Gly Tyr Phe Ala Tyr Ser His

100 105 110

Leu Glu Arg Ile Gly Ser Cys Ser Arg Gly Val Ser Lys Gln Arg Ile

115 120 125

Ile Gly Val Gly Glu Val Leu Asp Arg Gly Asp Glu Val Pro Ser Leu

130 135 140

Phe Met Thr Asn Val Trp Thr Pro Pro Asn Pro Asn Thr Val Tyr His

145 150 155 160

Cys Ser Ala Val Tyr Asn Asn Glu Phe Tyr Tyr Val Leu Cys Ala Val

165 170 175

Ser Thr Val Gly Asp Pro Ile Leu Asn Ser Thr Tyr Trp Ser Gly Ser

180 185 190

Leu Met Met Thr Arg Leu Ala Val Lys Pro Lys Ser Asn Gly Gly Gly

195 200 205

Tyr Asn Gln His Gln Leu Ala Leu Arg Ser Ile Glu Lys Gly Arg Tyr

210 215 220

Asp Lys Val Met Pro Tyr Gly Pro Ser Gly Ile Lys Gln Gly Asp Thr

225 230 235 240

Leu Tyr Phe Pro Ala Val Gly Phe Leu Val Arg Thr Glu Phe Lys Tyr

245 250 255

Asn Asp Ser Asn Cys Pro Ile Thr Lys Cys Gln Tyr Ser Lys Pro Glu

260 265 270

Asn Cys Arg Leu Ser Met Gly Ile Arg Pro Asn Ser His Tyr Ile Leu

275 280 285

Arg Ser Gly Leu Leu Lys Tyr Asn Leu Ser Asp Gly Glu Asn Pro Lys

290 295 300

Val Val Phe Ile Glu Ile Ser Asp Gln Arg Leu Ser Ile Gly Ser Pro

305 310 315 320

Ser Lys Ile Tyr Asp Ser Leu Gly Gln Pro Val Phe Tyr Gln Ala Ser

325 330 335

Phe Ser Trp Asp Thr Met Ile Lys Phe Gly Asp Val Leu Thr Val Asn

340 345 350

Pro Leu Val Val Asn Trp Arg Asn Asn Thr Val Ile Ser Arg Pro Gly

355 360 365

Gln Ser Gln Cys Pro Arg Phe Asn Thr Cys Pro Glu Ile Cys Trp Glu

370 375 380

Gly Val Tyr Asn Asp Ala Phe Leu Ile Asp Arg Ile Asn Trp Ile Ser

385 390 395 400

Ala Gly Val Phe Leu Asp Ser Asn Gln Thr Ala Glu Asn Pro Val Phe

405 410 415

Thr Val Phe Lys Asp Asn Glu Ile Leu Tyr Arg Ala Gln Leu Ala Ser

420 425 430

Glu Asp Thr Asn Ala Gln Lys Thr Ile Thr Asn Cys Phe Leu Leu Lys

435 440 445

Asn Lys Ile Trp Cys Ile Ser Leu Val Glu Ile Tyr Asp Thr Gly Asp

450 455 460

Asn Val Ile Arg Pro Lys Leu Phe Ala Val Lys Ile Pro Glu Gln Cys

465 470 475 480

Thr Gly Gly Gly Ser Gly Gly Asp Ile Ile Lys Leu Leu Asn Glu Gln

485 490 495

Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser Met Ser Ser

500 505 510

Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe Leu Phe Asp

515 520 525

His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile Ile Phe Leu

530 535 540

Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser Ala Pro Glu

545 550 555 560

His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala Tyr Glu His

565 570 575

Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp His Ala Ile

580 585 590

Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp Tyr Val Ala

595 600 605

Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu Asp Lys Ile

610 615 620

Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala Asp Gln Tyr

625 630 635 640

Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser

645 650

<210> 39

<211> 661

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒G序列

<400> 39

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln His His His His His His Gly Ser Ala Trp Ser

20 25 30

His Pro Gln Phe Glu Lys Gly Gly Leu Val Pro Arg Gly Ser Gly Asn

35 40 45

Ser Gln Arg Pro Gln Thr Glu Gly Val Ser Asn Leu Val Gly Leu Pro

50 55 60

Asn Asn Ile Cys Leu Gln Lys Thr Ser Asn Gln Ile Leu Lys Pro Lys

65 70 75 80

Leu Ile Ser Tyr Thr Leu Pro Val Val Gly Gln Ser Gly Thr Cys Ile

85 90 95

Thr Asp Pro Leu Leu Ala Met Asp Glu Gly Tyr Phe Ala Tyr Ser His

100 105 110

Leu Glu Arg Ile Gly Ser Cys Ser Arg Gly Val Ser Lys Gln Arg Ile

115 120 125

Ile Gly Val Gly Glu Val Leu Asp Arg Gly Asp Glu Val Pro Ser Leu

130 135 140

Phe Met Thr Asn Val Trp Thr Pro Pro Asn Pro Asn Thr Val Tyr His

145 150 155 160

Cys Ser Ala Val Tyr Asn Asn Glu Phe Tyr Tyr Val Leu Cys Ala Val

165 170 175

Ser Thr Val Gly Asp Pro Ile Leu Asn Ser Thr Tyr Trp Ser Gly Ser

180 185 190

Leu Met Met Thr Arg Leu Ala Val Lys Pro Lys Ser Asn Gly Gly Gly

195 200 205

Tyr Asn Gln His Gln Leu Ala Leu Arg Ser Ile Glu Lys Gly Arg Tyr

210 215 220

Asp Lys Val Met Pro Tyr Gly Pro Ser Gly Ile Lys Gln Gly Asp Thr

225 230 235 240

Leu Tyr Phe Pro Ala Val Gly Phe Leu Val Arg Thr Glu Phe Lys Tyr

245 250 255

Asn Asp Ser Asn Cys Pro Ile Thr Lys Cys Gln Tyr Ser Lys Pro Glu

260 265 270

Asn Cys Arg Leu Ser Met Gly Ile Arg Pro Asn Ser His Tyr Ile Leu

275 280 285

Arg Ser Gly Leu Leu Lys Tyr Asn Leu Ser Asp Gly Glu Asn Pro Lys

290 295 300

Val Val Phe Ile Glu Ile Ser Asp Gln Arg Leu Ser Ile Gly Ser Pro

305 310 315 320

Ser Lys Ile Tyr Asp Ser Leu Gly Gln Pro Val Phe Tyr Gln Ala Ser

325 330 335

Phe Ser Trp Asp Thr Met Ile Lys Phe Gly Asp Val Leu Thr Val Asn

340 345 350

Pro Leu Val Val Asn Trp Arg Asn Asn Thr Val Ile Ser Arg Pro Gly

355 360 365

Gln Ser Gln Cys Pro Arg Phe Asn Thr Cys Pro Glu Ile Cys Trp Glu

370 375 380

Gly Val Tyr Asn Asp Ala Phe Leu Ile Asp Arg Ile Asn Trp Ile Ser

385 390 395 400

Ala Gly Val Phe Leu Asp Ser Asn Gln Thr Ala Glu Asn Pro Val Phe

405 410 415

Thr Val Phe Lys Asp Asn Glu Ile Leu Tyr Arg Ala Gln Leu Ala Ser

420 425 430

Glu Asp Thr Asn Ala Gln Lys Thr Ile Thr Asn Cys Phe Leu Leu Lys

435 440 445

Asn Lys Ile Trp Cys Ile Ser Leu Val Glu Ile Tyr Asp Thr Gly Asp

450 455 460

Asn Val Ile Arg Pro Lys Leu Phe Ala Val Lys Ile Pro Glu Gln Cys

465 470 475 480

Thr Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Ser Gly Gly Gly

485 490 495

Asp Ile Ile Lys Leu Leu Asn Glu Gln Val Asn Lys Glu Met Gln Ser

500 505 510

Ser Asn Leu Tyr Met Ser Met Ser Ser Trp Cys Tyr Thr His Ser Leu

515 520 525

Asp Gly Ala Gly Leu Phe Leu Phe Asp His Ala Ala Glu Glu Tyr Glu

530 535 540

His Ala Lys Lys Leu Ile Ile Phe Leu Asn Glu Asn Asn Val Pro Val

545 550 555 560

Gln Leu Thr Ser Ile Ser Ala Pro Glu His Lys Phe Glu Gly Leu Thr

565 570 575

Gln Ile Phe Gln Lys Ala Tyr Glu His Glu Gln His Ile Ser Glu Ser

580 585 590

Ile Asn Asn Ile Val Asp His Ala Ile Lys Ser Lys Asp His Ala Thr

595 600 605

Phe Asn Phe Leu Gln Trp Tyr Val Ala Glu Gln His Glu Glu Glu Val

610 615 620

Leu Phe Lys Asp Ile Leu Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn

625 630 635 640

His Gly Leu Tyr Leu Ala Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser

645 650 655

Arg Lys Ser Gly Ser

660

<210> 40

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<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒G序列

<400> 40

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln His His His His His His Gly Ser Ala Trp Ser

20 25 30

His Pro Gln Phe Glu Lys Gly Gly Leu Val Pro Arg Gly Ser Gly Asn

35 40 45

Ser Gln Arg Pro Gln Thr Glu Gly Val Ser Asn Leu Val Gly Leu Pro

50 55 60

Asn Asn Ile Cys Leu Gln Lys Thr Ser Asn Gln Ile Leu Lys Pro Lys

65 70 75 80

Leu Ile Ser Tyr Thr Leu Pro Val Val Gly Gln Ser Gly Thr Cys Ile

85 90 95

Thr Asp Pro Leu Leu Ala Met Asp Glu Gly Tyr Phe Ala Tyr Ser His

100 105 110

Leu Glu Arg Ile Gly Ser Cys Ser Arg Gly Val Ser Lys Gln Arg Ile

115 120 125

Ile Gly Val Gly Glu Val Leu Asp Arg Gly Asp Glu Val Pro Ser Leu

130 135 140

Phe Met Thr Asn Val Trp Thr Pro Pro Asn Pro Asn Thr Val Tyr His

145 150 155 160

Cys Ser Ala Val Tyr Asn Asn Glu Phe Tyr Tyr Val Leu Cys Ala Val

165 170 175

Ser Thr Val Gly Asp Pro Ile Leu Asn Ser Thr Tyr Trp Ser Gly Ser

180 185 190

Leu Met Met Thr Arg Leu Ala Val Lys Pro Lys Ser Asn Gly Gly Gly

195 200 205

Tyr Asn Gln His Gln Leu Ala Leu Arg Ser Ile Glu Lys Gly Arg Tyr

210 215 220

Asp Lys Val Met Pro Tyr Gly Pro Ser Gly Ile Lys Gln Gly Asp Thr

225 230 235 240

Leu Tyr Phe Pro Ala Val Gly Phe Leu Val Arg Thr Glu Phe Lys Tyr

245 250 255

Asn Asp Ser Asn Cys Pro Ile Thr Lys Cys Gln Tyr Ser Lys Pro Glu

260 265 270

Asn Cys Arg Leu Ser Met Gly Ile Arg Pro Asn Ser His Tyr Ile Leu

275 280 285

Arg Ser Gly Leu Leu Lys Tyr Asn Leu Ser Asp Gly Glu Asn Pro Lys

290 295 300

Val Val Phe Ile Glu Ile Ser Asp Gln Arg Leu Ser Ile Gly Ser Pro

305 310 315 320

Ser Lys Ile Tyr Asp Ser Leu Gly Gln Pro Val Phe Tyr Gln Ala Ser

325 330 335

Phe Ser Trp Asp Thr Met Ile Lys Phe Gly Asp Val Leu Thr Val Asn

340 345 350

Pro Leu Val Val Asn Trp Arg Asn Asn Thr Val Ile Ser Arg Pro Gly

355 360 365

Gln Ser Gln Cys Pro Arg Phe Asn Thr Cys Pro Glu Ile Cys Trp Glu

370 375 380

Gly Val Tyr Asn Asp Ala Phe Leu Ile Asp Arg Ile Asn Trp Ile Ser

385 390 395 400

Ala Gly Val Phe Leu Asp Ser Asn Gln Thr Ala Glu Asn Pro Val Phe

405 410 415

Thr Val Phe Lys Asp Asn Glu Ile Leu Tyr Arg Ala Gln Leu Ala Ser

420 425 430

Glu Asp Thr Asn Ala Gln Lys Thr Ile Thr Asn Cys Phe Leu Leu Lys

435 440 445

Asn Lys Ile Trp Cys Ile Ser Leu Val Glu Ile Tyr Asp Thr Gly Asp

450 455 460

Asn Val Ile Arg Pro Lys Leu Phe Ala Val Lys Ile Pro Glu Gln Cys

465 470 475 480

Thr Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Ser Gly Gly Gly

485 490 495

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Asp Ile Ile Lys Leu Leu

500 505 510

Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser

515 520 525

Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe

530 535 540

Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile

545 550 555 560

Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser

565 570 575

Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala

580 585 590

Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp

595 600 605

His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp

610 615 620

Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu

625 630 635 640

Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala

645 650 655

Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser

660 665 670

<210> 41

<211> 681

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒G序列

<400> 41

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln His His His His His His Gly Ser Ala Trp Ser

20 25 30

His Pro Gln Phe Glu Lys Gly Gly Leu Val Pro Arg Gly Ser Gly Asn

35 40 45

Ser Gln Arg Pro Gln Thr Glu Gly Val Ser Asn Leu Val Gly Leu Pro

50 55 60

Asn Asn Ile Cys Leu Gln Lys Thr Ser Asn Gln Ile Leu Lys Pro Lys

65 70 75 80

Leu Ile Ser Tyr Thr Leu Pro Val Val Gly Gln Ser Gly Thr Cys Ile

85 90 95

Thr Asp Pro Leu Leu Ala Met Asp Glu Gly Tyr Phe Ala Tyr Ser His

100 105 110

Leu Glu Arg Ile Gly Ser Cys Ser Arg Gly Val Ser Lys Gln Arg Ile

115 120 125

Ile Gly Val Gly Glu Val Leu Asp Arg Gly Asp Glu Val Pro Ser Leu

130 135 140

Phe Met Thr Asn Val Trp Thr Pro Pro Asn Pro Asn Thr Val Tyr His

145 150 155 160

Cys Ser Ala Val Tyr Asn Asn Glu Phe Tyr Tyr Val Leu Cys Ala Val

165 170 175

Ser Thr Val Gly Asp Pro Ile Leu Asn Ser Thr Tyr Trp Ser Gly Ser

180 185 190

Leu Met Met Thr Arg Leu Ala Val Lys Pro Lys Ser Asn Gly Gly Gly

195 200 205

Tyr Asn Gln His Gln Leu Ala Leu Arg Ser Ile Glu Lys Gly Arg Tyr

210 215 220

Asp Lys Val Met Pro Tyr Gly Pro Ser Gly Ile Lys Gln Gly Asp Thr

225 230 235 240

Leu Tyr Phe Pro Ala Val Gly Phe Leu Val Arg Thr Glu Phe Lys Tyr

245 250 255

Asn Asp Ser Asn Cys Pro Ile Thr Lys Cys Gln Tyr Ser Lys Pro Glu

260 265 270

Asn Cys Arg Leu Ser Met Gly Ile Arg Pro Asn Ser His Tyr Ile Leu

275 280 285

Arg Ser Gly Leu Leu Lys Tyr Asn Leu Ser Asp Gly Glu Asn Pro Lys

290 295 300

Val Val Phe Ile Glu Ile Ser Asp Gln Arg Leu Ser Ile Gly Ser Pro

305 310 315 320

Ser Lys Ile Tyr Asp Ser Leu Gly Gln Pro Val Phe Tyr Gln Ala Ser

325 330 335

Phe Ser Trp Asp Thr Met Ile Lys Phe Gly Asp Val Leu Thr Val Asn

340 345 350

Pro Leu Val Val Asn Trp Arg Asn Asn Thr Val Ile Ser Arg Pro Gly

355 360 365

Gln Ser Gln Cys Pro Arg Phe Asn Thr Cys Pro Glu Ile Cys Trp Glu

370 375 380

Gly Val Tyr Asn Asp Ala Phe Leu Ile Asp Arg Ile Asn Trp Ile Ser

385 390 395 400

Ala Gly Val Phe Leu Asp Ser Asn Gln Thr Ala Glu Asn Pro Val Phe

405 410 415

Thr Val Phe Lys Asp Asn Glu Ile Leu Tyr Arg Ala Gln Leu Ala Ser

420 425 430

Glu Asp Thr Asn Ala Gln Lys Thr Ile Thr Asn Cys Phe Leu Leu Lys

435 440 445

Asn Lys Ile Trp Cys Ile Ser Leu Val Glu Ile Tyr Asp Thr Gly Asp

450 455 460

Asn Val Ile Arg Pro Lys Leu Phe Ala Val Lys Ile Pro Glu Gln Cys

465 470 475 480

Thr Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Ser Gly Gly Gly

485 490 495

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

500 505 510

Ser Gly Gly Gly Asp Ile Ile Lys Leu Leu Asn Glu Gln Val Asn Lys

515 520 525

Glu Met Gln Ser Ser Asn Leu Tyr Met Ser Met Ser Ser Trp Cys Tyr

530 535 540

Thr His Ser Leu Asp Gly Ala Gly Leu Phe Leu Phe Asp His Ala Ala

545 550 555 560

Glu Glu Tyr Glu His Ala Lys Lys Leu Ile Ile Phe Leu Asn Glu Asn

565 570 575

Asn Val Pro Val Gln Leu Thr Ser Ile Ser Ala Pro Glu His Lys Phe

580 585 590

Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala Tyr Glu His Glu Gln His

595 600 605

Ile Ser Glu Ser Ile Asn Asn Ile Val Asp His Ala Ile Lys Ser Lys

610 615 620

Asp His Ala Thr Phe Asn Phe Leu Gln Trp Tyr Val Ala Glu Gln His

625 630 635 640

Glu Glu Glu Val Leu Phe Lys Asp Ile Leu Asp Lys Ile Glu Leu Ile

645 650 655

Gly Asn Glu Asn His Gly Leu Tyr Leu Ala Asp Gln Tyr Val Lys Gly

660 665 670

Ile Ala Lys Ser Arg Lys Ser Gly Ser

675 680

<210> 42

<211> 647

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒G序列

<400> 42

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln His His His His His His Gly Ser Ala Trp Ser

20 25 30

His Pro Gln Phe Glu Lys Gly Gly Leu Val Pro Arg Gly Ser Gly Asn

35 40 45

Ser Gln Arg Pro Gln Thr Glu Gly Val Ser Asn Leu Val Gly Leu Pro

50 55 60

Asn Asn Ile Cys Leu Gln Lys Thr Ser Asn Gln Ile Leu Lys Pro Lys

65 70 75 80

Leu Ile Ser Tyr Thr Leu Pro Val Val Gly Gln Ser Gly Thr Cys Ile

85 90 95

Thr Asp Pro Leu Leu Ala Met Asp Glu Gly Tyr Phe Ala Tyr Ser His

100 105 110

Leu Glu Arg Ile Gly Ser Cys Ser Arg Gly Val Ser Lys Gln Arg Ile

115 120 125

Ile Gly Val Gly Glu Val Leu Asp Arg Gly Asp Glu Val Pro Ser Leu

130 135 140

Phe Met Thr Asn Val Trp Thr Pro Pro Asn Pro Asn Thr Val Tyr His

145 150 155 160

Cys Ser Ala Val Tyr Asn Asn Glu Phe Tyr Tyr Val Leu Cys Ala Val

165 170 175

Ser Thr Val Gly Asp Pro Ile Leu Asn Ser Thr Tyr Trp Ser Gly Ser

180 185 190

Leu Met Met Thr Arg Leu Ala Val Lys Pro Lys Ser Asn Gly Gly Gly

195 200 205

Tyr Asn Gln His Gln Leu Ala Leu Arg Ser Ile Glu Lys Gly Arg Tyr

210 215 220

Asp Lys Val Met Pro Tyr Gly Pro Ser Gly Ile Lys Gln Gly Asp Thr

225 230 235 240

Leu Tyr Phe Pro Ala Val Gly Phe Leu Val Arg Thr Glu Phe Lys Tyr

245 250 255

Asn Asp Ser Asn Cys Pro Ile Thr Lys Cys Gln Tyr Ser Lys Pro Glu

260 265 270

Asn Cys Arg Leu Ser Met Gly Ile Arg Pro Asn Ser His Tyr Ile Leu

275 280 285

Arg Ser Gly Leu Leu Lys Tyr Asn Leu Ser Asp Gly Glu Asn Pro Lys

290 295 300

Val Val Phe Ile Glu Ile Ser Asp Gln Arg Leu Ser Ile Gly Ser Pro

305 310 315 320

Ser Lys Ile Tyr Asp Ser Leu Gly Gln Pro Val Phe Tyr Gln Ala Ser

325 330 335

Phe Ser Trp Asp Thr Met Ile Lys Phe Gly Asp Val Leu Thr Val Asn

340 345 350

Pro Leu Val Val Asn Trp Arg Asn Asn Thr Val Ile Ser Arg Pro Gly

355 360 365

Gln Ser Gln Cys Pro Arg Phe Asn Thr Cys Pro Glu Ile Cys Trp Glu

370 375 380

Gly Val Tyr Asn Asp Ala Phe Leu Ile Asp Arg Ile Asn Trp Ile Ser

385 390 395 400

Ala Gly Val Phe Leu Asp Ser Asn Gln Thr Ala Glu Asn Pro Val Phe

405 410 415

Thr Val Phe Lys Asp Asn Glu Ile Leu Tyr Arg Ala Gln Leu Ala Ser

420 425 430

Glu Asp Thr Asn Ala Gln Lys Thr Ile Thr Asn Cys Phe Leu Leu Lys

435 440 445

Asn Lys Ile Trp Cys Ile Ser Leu Val Glu Ile Tyr Asp Thr Gly Asp

450 455 460

Asn Val Ile Arg Pro Lys Leu Phe Ala Val Lys Ile Pro Glu Gln Cys

465 470 475 480

Thr Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Met Gln Ile

485 490 495

Tyr Glu Gly Lys Leu Thr Ala Glu Gly Leu Arg Phe Gly Ile Val Ala

500 505 510

Ser Arg Phe Asn His Ala Leu Val Asp Arg Leu Val Glu Gly Ala Ile

515 520 525

Asp Cys Ile Val Arg His Gly Gly Arg Glu Glu Asp Ile Thr Leu Val

530 535 540

Arg Val Pro Gly Ser Trp Glu Ile Pro Val Ala Ala Gly Glu Leu Ala

545 550 555 560

Arg Lys Glu Asp Ile Asp Ala Val Ile Ala Ile Gly Val Leu Ile Arg

565 570 575

Gly Ala Thr Pro His Phe Asp Tyr Ile Ala Ser Glu Val Ser Lys Gly

580 585 590

Leu Ala Asp Leu Ser Leu Glu Leu Arg Lys Pro Ile Thr Phe Gly Val

595 600 605

Ile Thr Ala Asp Thr Leu Glu Gln Ala Ile Glu Arg Ala Gly Thr Lys

610 615 620

His Gly Asn Lys Gly Trp Glu Ala Ala Leu Ser Ala Ile Glu Met Ala

625 630 635 640

Asn Leu Phe Lys Ser Leu Arg

645

<210> 43

<211> 1005

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 43

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Gly Ile Leu His Tyr Glu Lys Leu Ser Lys Ile

20 25 30

Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro

35 40 45

Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn Val Ser Asn Met

50 55 60

Ser Gln Cys Thr Gly Ser Val Met Glu Asn Tyr Lys Thr Arg Leu Asn

65 70 75 80

Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile Tyr Lys Asn Asn

85 90 95

Thr His Asp Cys Val Gly Asp Val Arg Leu Ala Gly Val Cys Met Ala

100 105 110

Gly Val Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile Thr Ala Gly Val

115 120 125

Ala Leu Tyr Glu Ala Met Lys Asn Ala Asp Asn Ile Asn Lys Leu Lys

130 135 140

Ser Ser Ile Glu Ser Thr Asn Glu Ala Val Val Lys Leu Gln Glu Thr

145 150 155 160

Ala Glu Lys Thr Val Tyr Val Phe Thr Ala Leu Gln Asp Tyr Ile Asn

165 170 175

Thr Asn Leu Val Pro Thr Ile Asp Lys Ile Pro Cys Lys Gln Thr Glu

180 185 190

Leu Ser Leu Asp Leu Ala Leu Ser Lys Tyr Leu Ser Asp Leu Leu Phe

195 200 205

Val Phe Gly Pro Asn Leu Gln Asp Pro Val Ser Asn Ser Met Thr Ile

210 215 220

Gln Ala Ile Ser Gln Ala Phe Gly Gly Asn Tyr Glu Thr Leu Leu Arg

225 230 235 240

Thr Leu Gly Tyr Ala Thr Glu Asp Phe Asp Asp Leu Leu Glu Ser Asp

245 250 255

Ser Ile Thr Gly Gln Ile Ile Tyr Val Asp Leu Ser Ser Tyr Tyr Ile

260 265 270

Ile Val Arg Val Tyr Phe Pro Ile Leu Thr Glu Ile Gln Gln Ala Tyr

275 280 285

Ile Gln Glu Leu Leu Pro Val Ser Phe Asn Asn Asp Asn Ser Glu Trp

290 295 300

Ile Ser Ile Val Pro Asn Phe Ile Leu Val Arg Asn Thr Leu Ile Ser

305 310 315 320

Asn Ile Glu Ile Gly Phe Cys Leu Ile Thr Lys Arg Ser Val Ile Cys

325 330 335

Asn Gln Asp Tyr Ala Thr Pro Met Thr Asn Asn Met Arg Glu Cys Leu

340 345 350

Thr Gly Ser Thr Glu Lys Cys Pro Arg Glu Leu Val Val Ser Ser His

355 360 365

Val Pro Arg Phe Ala Leu Ser Asn Gly Val Leu Phe Ala Asn Cys Ile

370 375 380

Ser Val Thr Cys Gln Cys Gln Thr Thr Gly Arg Ala Ile Ser Gln Ser

385 390 395 400

Gly Glu Gln Thr Leu Leu Met Ile Asp Asn Thr Thr Cys Pro Thr Ala

405 410 415

Val Leu Gly Asn Val Ile Ile Ser Leu Gly Lys Tyr Leu Gly Ser Val

420 425 430

Asn Tyr Asn Ser Glu Gly Ile Ala Ile Gly Pro Pro Val Phe Thr Asp

435 440 445

Lys Val Asp Ile Ser Ser Gln Ile Ser Ser Met Asn Gln Ser Leu Gln

450 455 460

Gln Ser Lys Asp Tyr Ile Lys Glu Ala Gln Arg Leu Leu Asp Thr Val

465 470 475 480

Asn Pro Ser Leu Lys Leu Met Lys Gln Ile Glu Asp Lys Ile Glu Glu

485 490 495

Ile Leu Ser Lys Ile Tyr His Ile Glu Asn Glu Ile Ala Arg Ile Lys

500 505 510

Lys Leu Ile Gly Glu Ala Pro Gly Ser Gly Tyr Ile Pro Glu Ala Pro

515 520 525

Arg Asp Gly Gln Ala Tyr Val Arg Lys Asp Gly Glu Trp Val Leu Leu

530 535 540

Ser Thr Phe Leu Gly Ser Gly Gly Gly Gly Gly Gly Val Ser Asn Leu

545 550 555 560

Val Gly Leu Pro Asn Asn Ile Cys Leu Gln Lys Thr Ser Asn Gln Ile

565 570 575

Leu Lys Pro Lys Leu Ile Ser Tyr Thr Leu Pro Val Val Gly Gln Ser

580 585 590

Gly Thr Cys Ile Thr Asp Pro Leu Leu Ala Met Asp Glu Gly Tyr Phe

595 600 605

Ala Tyr Ser His Leu Glu Arg Ile Gly Ser Cys Ser Arg Gly Val Ser

610 615 620

Lys Gln Arg Ile Ile Gly Val Gly Glu Val Leu Asp Arg Gly Asp Glu

625 630 635 640

Val Pro Ser Leu Phe Met Thr Asn Val Trp Thr Pro Pro Asn Pro Asn

645 650 655

Thr Val Tyr His Cys Ser Ala Val Tyr Asn Asn Glu Phe Tyr Tyr Val

660 665 670

Leu Cys Ala Val Ser Thr Val Gly Asp Pro Ile Leu Asn Ser Thr Tyr

675 680 685

Trp Ser Gly Ser Leu Met Met Thr Arg Leu Ala Val Lys Pro Lys Ser

690 695 700

Asn Gly Gly Gly Tyr Asn Gln His Gln Leu Ala Leu Arg Ser Ile Glu

705 710 715 720

Lys Gly Arg Tyr Asp Lys Val Met Pro Tyr Gly Pro Ser Gly Ile Lys

725 730 735

Gln Gly Asp Thr Leu Tyr Phe Pro Ala Val Gly Phe Leu Val Arg Thr

740 745 750

Glu Phe Lys Tyr Asn Asp Ser Asn Cys Pro Ile Thr Lys Cys Gln Tyr

755 760 765

Ser Lys Pro Glu Asn Cys Arg Leu Ser Met Gly Ile Arg Pro Asn Ser

770 775 780

His Tyr Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn Leu Ser Asp Gly

785 790 795 800

Glu Asn Pro Lys Val Val Phe Ile Glu Ile Ser Asp Gln Arg Leu Ser

805 810 815

Ile Gly Ser Pro Ser Lys Ile Tyr Asp Ser Leu Gly Gln Pro Val Phe

820 825 830

Tyr Gln Ala Ser Phe Ser Trp Asp Thr Met Ile Lys Phe Gly Asp Val

835 840 845

Leu Thr Val Asn Pro Leu Val Val Asn Trp Arg Asn Asn Thr Val Ile

850 855 860

Ser Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn Thr Cys Pro Glu

865 870 875 880

Ile Cys Trp Glu Gly Val Tyr Asn Asp Ala Phe Leu Ile Asp Arg Ile

885 890 895

Asn Trp Ile Ser Ala Gly Val Phe Leu Asp Ser Asn Gln Thr Ala Glu

900 905 910

Asn Pro Val Phe Thr Val Phe Lys Asp Asn Glu Ile Leu Tyr Arg Ala

915 920 925

Gln Leu Ala Ser Glu Asp Thr Asn Ala Gln Lys Thr Ile Thr Asn Cys

930 935 940

Phe Leu Leu Lys Asn Lys Ile Trp Cys Ile Ser Leu Val Glu Ile Tyr

945 950 955 960

Asp Thr Gly Asp Asn Val Ile Arg Pro Lys Leu Phe Ala Val Lys Ile

965 970 975

Pro Glu Gln Cys Thr Gly Gly Leu Val Pro Arg Gly Ser His His His

980 985 990

His His His Ser Ala Trp Ser His Pro Gln Phe Glu Lys

995 1000 1005

<210> 44

<211> 1007

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 44

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Arg Pro Gln Thr Glu Gly Val Ser Asn Leu Val

20 25 30

Gly Leu Pro Asn Asn Ile Cys Leu Gln Lys Thr Ser Asn Gln Ile Leu

35 40 45

Lys Pro Lys Leu Ile Ser Tyr Thr Leu Pro Val Val Gly Gln Ser Gly

50 55 60

Thr Cys Ile Thr Asp Pro Leu Leu Ala Met Asp Glu Gly Tyr Phe Ala

65 70 75 80

Tyr Ser His Leu Glu Arg Ile Gly Ser Cys Ser Arg Gly Val Ser Lys

85 90 95

Gln Arg Ile Ile Gly Val Gly Glu Val Leu Asp Arg Gly Asp Glu Val

100 105 110

Pro Ser Leu Phe Met Thr Asn Val Trp Thr Pro Pro Asn Pro Asn Thr

115 120 125

Val Tyr His Cys Ser Ala Val Tyr Asn Asn Glu Phe Tyr Tyr Val Leu

130 135 140

Cys Ala Val Ser Thr Val Gly Asp Pro Ile Leu Asn Ser Thr Tyr Trp

145 150 155 160

Ser Gly Ser Leu Met Met Thr Arg Leu Ala Val Lys Pro Lys Ser Asn

165 170 175

Gly Gly Gly Tyr Asn Gln His Gln Leu Ala Leu Arg Ser Ile Glu Lys

180 185 190

Gly Arg Tyr Asp Lys Val Met Pro Tyr Gly Pro Ser Gly Ile Lys Gln

195 200 205

Gly Asp Thr Leu Tyr Phe Pro Ala Val Gly Phe Leu Val Arg Thr Glu

210 215 220

Phe Lys Tyr Asn Asp Ser Asn Cys Pro Ile Thr Lys Cys Gln Tyr Ser

225 230 235 240

Lys Pro Glu Asn Cys Arg Leu Ser Met Gly Ile Arg Pro Asn Ser His

245 250 255

Tyr Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn Leu Ser Asp Gly Glu

260 265 270

Asn Pro Lys Val Val Phe Ile Glu Ile Ser Asp Gln Arg Leu Ser Ile

275 280 285

Gly Ser Pro Ser Lys Ile Tyr Asp Ser Leu Gly Gln Pro Val Phe Tyr

290 295 300

Gln Ala Ser Phe Ser Trp Asp Thr Met Ile Lys Phe Gly Asp Val Leu

305 310 315 320

Thr Val Asn Pro Leu Val Val Asn Trp Arg Asn Asn Thr Val Ile Ser

325 330 335

Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn Thr Cys Pro Glu Ile

340 345 350

Cys Trp Glu Gly Val Tyr Asn Asp Ala Phe Leu Ile Asp Arg Ile Asn

355 360 365

Trp Ile Ser Ala Gly Val Phe Leu Asp Ser Asn Gln Thr Ala Glu Asn

370 375 380

Pro Val Phe Thr Val Phe Lys Asp Asn Glu Ile Leu Tyr Arg Ala Gln

385 390 395 400

Leu Ala Ser Glu Asp Thr Asn Ala Gln Lys Thr Ile Thr Asn Cys Phe

405 410 415

Leu Leu Lys Asn Lys Ile Trp Cys Ile Ser Leu Val Glu Ile Tyr Asp

420 425 430

Thr Gly Asp Asn Val Ile Arg Pro Lys Leu Phe Ala Val Lys Ile Pro

435 440 445

Glu Gln Cys Thr Gly Gly Gly Gln Gly Ile Leu His Tyr Glu Lys Leu

450 455 460

Ser Lys Ile Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile Lys

465 470 475 480

Ser Asn Pro Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn Val

485 490 495

Ser Asn Met Ser Gln Cys Thr Gly Ser Val Met Glu Asn Tyr Lys Thr

500 505 510

Arg Leu Asn Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile Tyr

515 520 525

Lys Asn Asn Thr His Asp Cys Val Gly Asp Val Arg Leu Ala Gly Val

530 535 540

Cys Met Ala Gly Val Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile Thr

545 550 555 560

Ala Gly Val Ala Leu Tyr Glu Ala Met Lys Asn Ala Asp Asn Ile Asn

565 570 575

Lys Leu Lys Ser Ser Ile Glu Ser Thr Asn Glu Ala Val Val Lys Leu

580 585 590

Gln Glu Thr Ala Glu Lys Thr Val Tyr Val Phe Thr Ala Leu Gln Asp

595 600 605

Tyr Ile Asn Thr Asn Leu Val Pro Thr Ile Asp Lys Ile Pro Cys Lys

610 615 620

Gln Thr Glu Leu Ser Leu Asp Leu Ala Leu Ser Lys Tyr Leu Ser Asp

625 630 635 640

Leu Leu Phe Val Phe Gly Pro Asn Leu Gln Asp Pro Val Ser Asn Ser

645 650 655

Met Thr Ile Gln Ala Ile Ser Gln Ala Phe Gly Gly Asn Tyr Glu Thr

660 665 670

Leu Leu Arg Thr Leu Gly Tyr Ala Thr Glu Asp Phe Asp Asp Leu Leu

675 680 685

Glu Ser Asp Ser Ile Thr Gly Gln Ile Ile Tyr Val Asp Leu Ser Ser

690 695 700

Tyr Tyr Ile Ile Val Arg Val Tyr Phe Pro Ile Leu Thr Glu Ile Gln

705 710 715 720

Gln Ala Tyr Ile Gln Glu Leu Leu Pro Val Ser Phe Asn Asn Asp Asn

725 730 735

Ser Glu Trp Ile Ser Ile Val Pro Asn Phe Ile Leu Val Arg Asn Thr

740 745 750

Leu Ile Ser Asn Ile Glu Ile Gly Phe Cys Leu Ile Thr Lys Arg Ser

755 760 765

Val Ile Cys Asn Gln Asp Tyr Ala Thr Pro Met Thr Asn Asn Met Arg

770 775 780

Glu Cys Leu Thr Gly Ser Thr Glu Lys Cys Pro Arg Glu Leu Val Val

785 790 795 800

Ser Ser His Val Pro Arg Phe Ala Leu Ser Asn Gly Val Leu Phe Ala

805 810 815

Asn Cys Ile Ser Val Thr Cys Gln Cys Gln Thr Thr Gly Arg Ala Ile

820 825 830

Ser Gln Ser Gly Glu Gln Thr Leu Leu Met Ile Asp Asn Thr Thr Cys

835 840 845

Pro Thr Ala Val Leu Gly Asn Val Ile Ile Ser Leu Gly Lys Tyr Leu

850 855 860

Gly Ser Val Asn Tyr Asn Ser Glu Gly Ile Ala Ile Gly Pro Pro Val

865 870 875 880

Phe Thr Asp Lys Val Asp Ile Ser Ser Gln Ile Ser Ser Met Asn Gln

885 890 895

Ser Leu Gln Gln Ser Lys Asp Tyr Ile Lys Glu Ala Gln Arg Leu Leu

900 905 910

Asp Thr Val Asn Pro Ser Leu Lys Leu Met Lys Gln Ile Glu Asp Lys

915 920 925

Ile Glu Glu Ile Leu Ser Lys Ile Tyr His Ile Glu Asn Glu Ile Ala

930 935 940

Arg Ile Lys Lys Leu Ile Gly Glu Ala Pro Gly Ser Gly Tyr Ile Pro

945 950 955 960

Glu Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys Asp Gly Glu Trp

965 970 975

Val Leu Leu Ser Thr Phe Leu Gly Ser Leu Val Pro Arg Gly Ser His

980 985 990

His His His His His Ser Ala Trp Ser His Pro Gln Phe Glu Lys

995 1000 1005

<210> 45

<211> 991

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 45

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Gly Ile Leu His Tyr Glu Lys Leu Ser Lys Ile

20 25 30

Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro

35 40 45

Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn Val Ser Asn Met

50 55 60

Ser Gln Cys Thr Gly Ser Val Met Glu Asn Tyr Lys Thr Arg Leu Asn

65 70 75 80

Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile Tyr Lys Asn Gly

85 90 95

Gly Ser Gly Val Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile Thr Ala

100 105 110

Gly Val Ala Leu Tyr Glu Ala Met Lys Asn Ala Asp Asn Ile Asn Lys

115 120 125

Leu Lys Ser Ser Ile Glu Ser Thr Asn Glu Ala Val Val Lys Leu Gln

130 135 140

Glu Thr Ala Glu Lys Thr Val Tyr Val Leu Thr Ala Leu Gln Asp Tyr

145 150 155 160

Ile Asn Thr Asn Leu Val Pro Thr Ile Asp Lys Ile Ser Cys Lys Gln

165 170 175

Thr Glu Leu Ser Leu Asp Leu Ala Leu Ser Lys Tyr Leu Ser Asp Leu

180 185 190

Leu Phe Val Phe Gly Pro Asn Leu Gln Asp Pro Val Ser Asn Ser Met

195 200 205

Thr Ile Gln Ala Ile Ser Gln Ala Phe Gly Gly Asn Tyr Glu Thr Leu

210 215 220

Leu Arg Thr Leu Gly Tyr Ala Thr Glu Asp Phe Asp Asp Leu Leu Glu

225 230 235 240

Ser Asp Ser Ile Thr Gly Gln Ile Ile Tyr Val Asp Leu Ser Ser Tyr

245 250 255

Tyr Ile Ile Val Arg Val Tyr Phe Pro Ile Leu Thr Glu Ile Gln Gln

260 265 270

Ala Tyr Ile Gln Glu Leu Leu Pro Val Ser Phe Asn Asn Asp Asn Ser

275 280 285

Glu Trp Ile Ser Ile Val Pro Asn Phe Ile Leu Val Arg Asn Thr Leu

290 295 300

Ile Ser Asn Ile Glu Ile Gly Phe Cys Leu Ile Thr Lys Arg Ser Val

305 310 315 320

Ile Cys Asn Gln Asp Tyr Ala Thr Pro Met Thr Asn Asn Met Arg Glu

325 330 335

Cys Leu Thr Gly Ser Thr Glu Lys Cys Pro Arg Glu Leu Val Val Ser

340 345 350

Ser His Val Pro Arg Phe Ala Leu Ser Asn Gly Val Leu Phe Ala Asn

355 360 365

Cys Ile Ser Val Thr Cys Gln Cys Gln Thr Thr Gly Arg Ala Ile Ser

370 375 380

Gln Ser Gly Glu Gln Thr Leu Leu Met Ile Asp Asn Thr Thr Cys Pro

385 390 395 400

Thr Ala Val Leu Gly Asn Val Ile Ile Ser Leu Gly Lys Tyr Leu Gly

405 410 415

Ser Val Asn Tyr Asn Ser Glu Gly Ile Ala Ile Gly Pro Pro Val Phe

420 425 430

Thr Asp Lys Val Asp Ile Ser Ser Gln Ile Ser Ser Met Asn Gln Ser

435 440 445

Leu Gln Gln Ser Lys Asp Tyr Ile Lys Glu Ala Gln Arg Leu Leu Asp

450 455 460

Thr Val Asn Pro Ser Leu Lys Leu Met Lys Gln Ile Glu Asp Lys Ile

465 470 475 480

Glu Glu Ile Leu Ser Lys Ile Tyr His Ile Glu Asn Glu Ile Ala Arg

485 490 495

Ile Lys Lys Leu Ile Gly Glu Ala Pro Gly Ser Gly Tyr Ile Pro Glu

500 505 510

Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys Asp Gly Glu Trp Val

515 520 525

Leu Leu Ser Thr Phe Leu Gly Ser Gly Gly Gly Gly Gly Gly Val Ser

530 535 540

Asn Leu Val Gly Leu Pro Asn Asn Ile Cys Leu Gln Lys Thr Ser Asn

545 550 555 560

Gln Ile Leu Lys Pro Lys Leu Ile Ser Tyr Thr Leu Pro Val Val Gly

565 570 575

Gln Ser Gly Thr Cys Ile Thr Asp Pro Leu Leu Ala Met Asp Glu Gly

580 585 590

Tyr Phe Ala Tyr Ser His Leu Glu Arg Ile Gly Ser Cys Ser Arg Gly

595 600 605

Val Ser Lys Gln Arg Ile Ile Gly Val Gly Glu Val Leu Asp Arg Gly

610 615 620

Asp Glu Val Pro Ser Leu Phe Met Thr Asn Val Trp Thr Pro Pro Asn

625 630 635 640

Pro Asn Thr Val Tyr His Cys Ser Ala Val Tyr Asn Asn Glu Phe Tyr

645 650 655

Tyr Val Leu Cys Ala Val Ser Thr Val Gly Asp Pro Ile Leu Asn Ser

660 665 670

Thr Tyr Trp Ser Gly Ser Leu Met Met Thr Arg Leu Ala Val Lys Pro

675 680 685

Lys Ser Asn Gly Gly Gly Tyr Asn Gln His Gln Leu Ala Leu Arg Ser

690 695 700

Ile Glu Lys Gly Arg Tyr Asp Lys Val Met Pro Tyr Gly Pro Ser Gly

705 710 715 720

Ile Lys Gln Gly Asp Thr Leu Tyr Phe Pro Ala Val Gly Phe Leu Val

725 730 735

Arg Thr Glu Phe Lys Tyr Asn Asp Ser Asn Cys Pro Ile Thr Lys Cys

740 745 750

Gln Tyr Ser Lys Pro Glu Asn Cys Arg Leu Ser Met Gly Ile Arg Pro

755 760 765

Asn Ser His Tyr Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn Leu Ser

770 775 780

Asp Gly Glu Asn Pro Lys Val Val Phe Ile Glu Ile Ser Asp Gln Arg

785 790 795 800

Leu Ser Ile Gly Ser Pro Ser Lys Ile Tyr Asp Ser Leu Gly Gln Pro

805 810 815

Val Phe Tyr Gln Ala Ser Phe Ser Trp Asp Thr Met Ile Lys Phe Gly

820 825 830

Asp Val Leu Thr Val Asn Pro Leu Val Val Asn Trp Arg Asn Asn Thr

835 840 845

Val Ile Ser Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn Thr Cys

850 855 860

Pro Glu Ile Cys Trp Glu Gly Val Tyr Asn Asp Ala Phe Leu Ile Asp

865 870 875 880

Arg Ile Asn Trp Ile Ser Ala Gly Val Phe Leu Asp Ser Asn Gln Thr

885 890 895

Ala Glu Asn Pro Val Phe Thr Val Phe Lys Asp Asn Glu Ile Leu Tyr

900 905 910

Arg Ala Gln Leu Ala Ser Glu Asp Thr Asn Ala Gln Lys Thr Ile Thr

915 920 925

Asn Cys Phe Leu Leu Lys Asn Lys Ile Trp Cys Ile Ser Leu Val Glu

930 935 940

Ile Tyr Asp Thr Gly Asp Asn Val Ile Arg Pro Lys Leu Phe Ala Val

945 950 955 960

Lys Ile Pro Glu Gln Cys Thr Gly Gly Leu Val Pro Arg Gly Ser His

965 970 975

His His His His His Ser Ala Trp Ser His Pro Gln Phe Glu Lys

980 985 990

<210> 46

<211> 1423

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 46

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Gly Ile Leu His Tyr Glu Lys Leu Ser Lys Ile

20 25 30

Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro

35 40 45

Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn Val Ser Asn Met

50 55 60

Ser Gln Cys Thr Gly Ser Val Met Glu Asn Tyr Lys Thr Arg Leu Asn

65 70 75 80

Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile Tyr Lys Asn Gly

85 90 95

Gly Ser Gly Val Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile Thr Ala

100 105 110

Gly Val Ala Leu Tyr Glu Ala Met Lys Asn Ala Asp Asn Ile Asn Lys

115 120 125

Leu Lys Ser Ser Ile Glu Ser Thr Asn Glu Ala Val Val Lys Leu Gln

130 135 140

Glu Thr Ala Glu Lys Thr Val Tyr Val Leu Thr Ala Leu Gln Asp Tyr

145 150 155 160

Ile Asn Thr Asn Leu Val Pro Thr Ile Asp Lys Ile Ser Cys Lys Gln

165 170 175

Thr Glu Leu Ser Leu Asp Leu Ala Leu Ser Lys Tyr Leu Ser Asp Leu

180 185 190

Leu Phe Val Phe Gly Pro Asn Leu Gln Asp Pro Val Ser Asn Ser Met

195 200 205

Thr Ile Gln Ala Ile Ser Gln Ala Phe Gly Gly Asn Tyr Glu Thr Leu

210 215 220

Leu Arg Thr Leu Gly Tyr Ala Thr Glu Asp Phe Asp Asp Leu Leu Glu

225 230 235 240

Ser Asp Ser Ile Thr Gly Gln Ile Ile Tyr Val Asp Leu Ser Ser Tyr

245 250 255

Tyr Ile Ile Val Arg Val Tyr Phe Pro Ile Leu Thr Glu Ile Gln Gln

260 265 270

Ala Tyr Ile Gln Glu Leu Leu Pro Val Ser Phe Asn Asn Asp Asn Ser

275 280 285

Glu Trp Ile Ser Ile Val Pro Asn Phe Ile Leu Val Arg Asn Thr Leu

290 295 300

Ile Ser Asn Ile Glu Ile Gly Phe Cys Leu Ile Thr Lys Arg Ser Val

305 310 315 320

Ile Cys Asn Gln Asp Tyr Ala Thr Pro Met Thr Asn Asn Met Arg Glu

325 330 335

Cys Leu Thr Gly Ser Thr Glu Lys Cys Pro Arg Glu Leu Val Val Ser

340 345 350

Ser His Val Pro Arg Phe Ala Leu Ser Asn Gly Val Leu Phe Ala Asn

355 360 365

Cys Ile Ser Val Thr Cys Gln Cys Gln Thr Thr Gly Arg Ala Ile Ser

370 375 380

Gln Ser Gly Glu Gln Thr Leu Leu Met Ile Asp Asn Thr Thr Cys Pro

385 390 395 400

Thr Ala Val Leu Gly Asn Val Ile Ile Ser Leu Gly Lys Tyr Leu Gly

405 410 415

Ser Val Asn Tyr Asn Ser Glu Gly Ile Ala Ile Gly Pro Pro Val Phe

420 425 430

Thr Asp Lys Val Asp Ile Ser Ser Gln Ile Ser Ser Met Asn Gln Ser

435 440 445

Leu Gln Gln Ser Lys Asp Tyr Ile Lys Glu Ala Gln Arg Leu Leu Asp

450 455 460

Thr Val Asn Pro Ser Leu Lys Leu Met Lys Gln Ile Glu Asp Lys Ile

465 470 475 480

Glu Glu Ile Leu Ser Lys Ile Tyr His Ile Glu Asn Glu Ile Ala Arg

485 490 495

Ile Lys Lys Leu Ile Gly Glu Ala Pro Gly Ser Gly Tyr Ile Pro Glu

500 505 510

Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys Asp Gly Glu Trp Val

515 520 525

Leu Leu Ser Thr Phe Leu Gly Ser Gly Gly Gly Gly Gly Gly Val Ser

530 535 540

Asn Leu Val Gly Leu Pro Asn Asn Ile Cys Leu Gln Lys Thr Ser Asn

545 550 555 560

Gln Ile Leu Lys Pro Lys Leu Ile Ser Tyr Thr Leu Pro Val Val Gly

565 570 575

Gln Ser Gly Thr Cys Ile Thr Asp Pro Leu Leu Ala Met Asp Glu Gly

580 585 590

Tyr Phe Ala Tyr Ser His Leu Glu Arg Ile Gly Ser Cys Ser Arg Gly

595 600 605

Val Ser Lys Gln Arg Ile Ile Gly Val Gly Glu Val Leu Asp Arg Gly

610 615 620

Asp Glu Val Pro Ser Leu Phe Met Thr Asn Val Trp Thr Pro Pro Asn

625 630 635 640

Pro Asn Thr Val Tyr His Cys Ser Ala Val Tyr Asn Asn Glu Phe Tyr

645 650 655

Tyr Val Leu Cys Ala Val Ser Thr Val Gly Asp Pro Ile Leu Asn Ser

660 665 670

Thr Tyr Trp Ser Gly Ser Leu Met Met Thr Arg Leu Ala Val Lys Pro

675 680 685

Lys Ser Asn Gly Gly Gly Tyr Asn Gln His Gln Leu Ala Leu Arg Ser

690 695 700

Ile Glu Lys Gly Arg Tyr Asp Lys Val Met Pro Tyr Gly Pro Ser Gly

705 710 715 720

Ile Lys Gln Gly Asp Thr Leu Tyr Phe Pro Ala Val Gly Phe Leu Val

725 730 735

Arg Thr Glu Phe Lys Tyr Asn Asp Ser Asn Cys Pro Ile Thr Lys Cys

740 745 750

Gln Tyr Ser Lys Pro Glu Asn Cys Arg Leu Ser Met Gly Ile Arg Pro

755 760 765

Asn Ser His Tyr Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn Leu Ser

770 775 780

Asp Gly Glu Asn Pro Lys Val Val Phe Ile Glu Ile Ser Asp Gln Arg

785 790 795 800

Leu Ser Ile Gly Ser Pro Ser Lys Ile Tyr Asp Ser Leu Gly Gln Pro

805 810 815

Val Phe Tyr Gln Ala Ser Phe Ser Trp Asp Thr Met Ile Lys Phe Gly

820 825 830

Asp Val Leu Thr Val Asn Pro Leu Val Val Asn Trp Arg Asn Asn Thr

835 840 845

Val Ile Ser Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn Thr Cys

850 855 860

Pro Glu Ile Cys Trp Glu Gly Val Tyr Asn Asp Ala Phe Leu Ile Asp

865 870 875 880

Arg Ile Asn Trp Ile Ser Ala Gly Val Phe Leu Asp Ser Asn Gln Thr

885 890 895

Ala Glu Asn Pro Val Phe Thr Val Phe Lys Asp Asn Glu Ile Leu Tyr

900 905 910

Arg Ala Gln Leu Ala Ser Glu Asp Thr Asn Ala Gln Lys Thr Ile Thr

915 920 925

Asn Cys Phe Leu Leu Lys Asn Lys Ile Trp Cys Ile Ser Leu Val Glu

930 935 940

Ile Tyr Asp Thr Gly Asp Asn Val Ile Arg Pro Lys Leu Phe Ala Val

945 950 955 960

Lys Ile Pro Glu Gln Cys Thr Gly Gly Gly Gly Gly Gly Gly Val Ser

965 970 975

Asn Leu Val Gly Leu Pro Asn Asn Ile Cys Leu Gln Lys Thr Ser Asn

980 985 990

Gln Ile Leu Lys Pro Lys Leu Ile Ser Tyr Thr Leu Pro Val Val Gly

995 1000 1005

Gln Ser Gly Thr Cys Ile Thr Asp Pro Leu Leu Ala Met Asp Glu

1010 1015 1020

Gly Tyr Phe Ala Tyr Ser His Leu Glu Arg Ile Gly Ser Cys Ser

1025 1030 1035

Arg Gly Val Ser Lys Gln Arg Ile Ile Gly Val Gly Glu Val Leu

1040 1045 1050

Asp Arg Gly Asp Glu Val Pro Ser Leu Phe Met Thr Asn Val Trp

1055 1060 1065

Thr Pro Pro Asn Pro Asn Thr Val Tyr His Cys Ser Ala Val Tyr

1070 1075 1080

Asn Asn Glu Phe Tyr Tyr Val Leu Cys Ala Val Ser Thr Val Gly

1085 1090 1095

Asp Pro Ile Leu Asn Ser Thr Tyr Trp Ser Gly Ser Leu Met Met

1100 1105 1110

Thr Arg Leu Ala Val Lys Pro Lys Ser Asn Gly Gly Gly Tyr Asn

1115 1120 1125

Gln His Gln Leu Ala Leu Arg Ser Ile Glu Lys Gly Arg Tyr Asp

1130 1135 1140

Lys Val Met Pro Tyr Gly Pro Ser Gly Ile Lys Gln Gly Asp Thr

1145 1150 1155

Leu Tyr Phe Pro Ala Val Gly Phe Leu Val Arg Thr Glu Phe Lys

1160 1165 1170

Tyr Asn Asp Ser Asn Cys Pro Ile Thr Lys Cys Gln Tyr Ser Lys

1175 1180 1185

Pro Glu Asn Cys Arg Leu Ser Met Gly Ile Arg Pro Asn Ser His

1190 1195 1200

Tyr Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn Leu Ser Asp Gly

1205 1210 1215

Glu Asn Pro Lys Val Val Phe Ile Glu Ile Ser Asp Gln Arg Leu

1220 1225 1230

Ser Ile Gly Ser Pro Ser Lys Ile Tyr Asp Ser Leu Gly Gln Pro

1235 1240 1245

Val Phe Tyr Gln Ala Ser Phe Ser Trp Asp Thr Met Ile Lys Phe

1250 1255 1260

Gly Asp Val Leu Thr Val Asn Pro Leu Val Val Asn Trp Arg Asn

1265 1270 1275

Asn Thr Val Ile Ser Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe

1280 1285 1290

Asn Thr Cys Pro Glu Ile Cys Trp Glu Gly Val Tyr Asn Asp Ala

1295 1300 1305

Phe Leu Ile Asp Arg Ile Asn Trp Ile Ser Ala Gly Val Phe Leu

1310 1315 1320

Asp Ser Asn Gln Thr Ala Glu Asn Pro Val Phe Thr Val Phe Lys

1325 1330 1335

Asp Asn Glu Ile Leu Tyr Arg Ala Gln Leu Ala Ser Glu Asp Thr

1340 1345 1350

Asn Ala Gln Lys Thr Ile Thr Asn Cys Phe Leu Leu Lys Asn Lys

1355 1360 1365

Ile Trp Cys Ile Ser Leu Val Glu Ile Tyr Asp Thr Gly Asp Asn

1370 1375 1380

Val Ile Arg Pro Lys Leu Phe Ala Val Lys Ile Pro Glu Gln Cys

1385 1390 1395

Thr Gly Gly Leu Val Pro Arg Gly Ser His His His His His His

1400 1405 1410

Ser Ala Trp Ser His Pro Gln Phe Glu Lys

1415 1420

<210> 47

<211> 1437

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 47

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Gly Ile Leu His Tyr Glu Lys Leu Ser Lys Ile

20 25 30

Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro

35 40 45

Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn Val Ser Asn Met

50 55 60

Ser Gln Cys Thr Gly Ser Val Met Glu Asn Tyr Lys Thr Arg Leu Asn

65 70 75 80

Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile Tyr Lys Asn Asn

85 90 95

Thr His Asp Cys Val Gly Asp Val Arg Leu Ala Gly Val Cys Met Ala

100 105 110

Gly Val Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile Thr Ala Gly Val

115 120 125

Ala Leu Tyr Glu Ala Met Lys Asn Ala Asp Asn Ile Asn Lys Leu Lys

130 135 140

Ser Ser Ile Glu Ser Thr Asn Glu Ala Val Val Lys Leu Gln Glu Thr

145 150 155 160

Ala Glu Lys Thr Val Tyr Val Phe Thr Ala Leu Gln Asp Tyr Ile Asn

165 170 175

Thr Asn Leu Val Pro Thr Ile Asp Lys Ile Pro Cys Lys Gln Thr Glu

180 185 190

Leu Ser Leu Asp Leu Ala Leu Ser Lys Tyr Leu Ser Asp Leu Leu Phe

195 200 205

Val Phe Gly Pro Asn Leu Gln Asp Pro Val Ser Asn Ser Met Thr Ile

210 215 220

Gln Ala Ile Ser Gln Ala Phe Gly Gly Asn Tyr Glu Thr Leu Leu Arg

225 230 235 240

Thr Leu Gly Tyr Ala Thr Glu Asp Phe Asp Asp Leu Leu Glu Ser Asp

245 250 255

Ser Ile Thr Gly Gln Ile Ile Tyr Val Asp Leu Ser Ser Tyr Tyr Ile

260 265 270

Ile Val Arg Val Tyr Phe Pro Ile Leu Thr Glu Ile Gln Gln Ala Tyr

275 280 285

Ile Gln Glu Leu Leu Pro Val Ser Phe Asn Asn Asp Asn Ser Glu Trp

290 295 300

Ile Ser Ile Val Pro Asn Phe Ile Leu Val Arg Asn Thr Leu Ile Ser

305 310 315 320

Asn Ile Glu Ile Gly Phe Cys Leu Ile Thr Lys Arg Ser Val Ile Cys

325 330 335

Asn Gln Asp Tyr Ala Thr Pro Met Thr Asn Asn Met Arg Glu Cys Leu

340 345 350

Thr Gly Ser Thr Glu Lys Cys Pro Arg Glu Leu Val Val Ser Ser His

355 360 365

Val Pro Arg Phe Ala Leu Ser Asn Gly Val Leu Phe Ala Asn Cys Ile

370 375 380

Ser Val Thr Cys Gln Cys Gln Thr Thr Gly Arg Ala Ile Ser Gln Ser

385 390 395 400

Gly Glu Gln Thr Leu Leu Met Ile Asp Asn Thr Thr Cys Pro Thr Ala

405 410 415

Val Leu Gly Asn Val Ile Ile Ser Leu Gly Lys Tyr Leu Gly Ser Val

420 425 430

Asn Tyr Asn Ser Glu Gly Ile Ala Ile Gly Pro Pro Val Phe Thr Asp

435 440 445

Lys Val Asp Ile Ser Ser Gln Ile Ser Ser Met Asn Gln Ser Leu Gln

450 455 460

Gln Ser Lys Asp Tyr Ile Lys Glu Ala Gln Arg Leu Leu Asp Thr Val

465 470 475 480

Asn Pro Ser Leu Lys Leu Met Lys Gln Ile Glu Asp Lys Ile Glu Glu

485 490 495

Ile Leu Ser Lys Ile Tyr His Ile Glu Asn Glu Ile Ala Arg Ile Lys

500 505 510

Lys Leu Ile Gly Glu Ala Pro Gly Ser Gly Tyr Ile Pro Glu Ala Pro

515 520 525

Arg Asp Gly Gln Ala Tyr Val Arg Lys Asp Gly Glu Trp Val Leu Leu

530 535 540

Ser Thr Phe Leu Gly Ser Gly Gly Gly Gly Gly Gly Val Ser Asn Leu

545 550 555 560

Val Gly Leu Pro Asn Asn Ile Cys Leu Gln Lys Thr Ser Asn Gln Ile

565 570 575

Leu Lys Pro Lys Leu Ile Ser Tyr Thr Leu Pro Val Val Gly Gln Ser

580 585 590

Gly Thr Cys Ile Thr Asp Pro Leu Leu Ala Met Asp Glu Gly Tyr Phe

595 600 605

Ala Tyr Ser His Leu Glu Arg Ile Gly Ser Cys Ser Arg Gly Val Ser

610 615 620

Lys Gln Arg Ile Ile Gly Val Gly Glu Val Leu Asp Arg Gly Asp Glu

625 630 635 640

Val Pro Ser Leu Phe Met Thr Asn Val Trp Thr Pro Pro Asn Pro Asn

645 650 655

Thr Val Tyr His Cys Ser Ala Val Tyr Asn Asn Glu Phe Tyr Tyr Val

660 665 670

Leu Cys Ala Val Ser Thr Val Gly Asp Pro Ile Leu Asn Ser Thr Tyr

675 680 685

Trp Ser Gly Ser Leu Met Met Thr Arg Leu Ala Val Lys Pro Lys Ser

690 695 700

Asn Gly Gly Gly Tyr Asn Gln His Gln Leu Ala Leu Arg Ser Ile Glu

705 710 715 720

Lys Gly Arg Tyr Asp Lys Val Met Pro Tyr Gly Pro Ser Gly Ile Lys

725 730 735

Gln Gly Asp Thr Leu Tyr Phe Pro Ala Val Gly Phe Leu Val Arg Thr

740 745 750

Glu Phe Lys Tyr Asn Asp Ser Asn Cys Pro Ile Thr Lys Cys Gln Tyr

755 760 765

Ser Lys Pro Glu Asn Cys Arg Leu Ser Met Gly Ile Arg Pro Asn Ser

770 775 780

His Tyr Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn Leu Ser Asp Gly

785 790 795 800

Glu Asn Pro Lys Val Val Phe Ile Glu Ile Ser Asp Gln Arg Leu Ser

805 810 815

Ile Gly Ser Pro Ser Lys Ile Tyr Asp Ser Leu Gly Gln Pro Val Phe

820 825 830

Tyr Gln Ala Ser Phe Ser Trp Asp Thr Met Ile Lys Phe Gly Asp Val

835 840 845

Leu Thr Val Asn Pro Leu Val Val Asn Trp Arg Asn Asn Thr Val Ile

850 855 860

Ser Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn Thr Cys Pro Glu

865 870 875 880

Ile Cys Trp Glu Gly Val Tyr Asn Asp Ala Phe Leu Ile Asp Arg Ile

885 890 895

Asn Trp Ile Ser Ala Gly Val Phe Leu Asp Ser Asn Gln Thr Ala Glu

900 905 910

Asn Pro Val Phe Thr Val Phe Lys Asp Asn Glu Ile Leu Tyr Arg Ala

915 920 925

Gln Leu Ala Ser Glu Asp Thr Asn Ala Gln Lys Thr Ile Thr Asn Cys

930 935 940

Phe Leu Leu Lys Asn Lys Ile Trp Cys Ile Ser Leu Val Glu Ile Tyr

945 950 955 960

Asp Thr Gly Asp Asn Val Ile Arg Pro Lys Leu Phe Ala Val Lys Ile

965 970 975

Pro Glu Gln Cys Thr Gly Gly Gly Gly Gly Gly Gly Val Ser Asn Leu

980 985 990

Val Gly Leu Pro Asn Asn Ile Cys Leu Gln Lys Thr Ser Asn Gln Ile

995 1000 1005

Leu Lys Pro Lys Leu Ile Ser Tyr Thr Leu Pro Val Val Gly Gln

1010 1015 1020

Ser Gly Thr Cys Ile Thr Asp Pro Leu Leu Ala Met Asp Glu Gly

1025 1030 1035

Tyr Phe Ala Tyr Ser His Leu Glu Arg Ile Gly Ser Cys Ser Arg

1040 1045 1050

Gly Val Ser Lys Gln Arg Ile Ile Gly Val Gly Glu Val Leu Asp

1055 1060 1065

Arg Gly Asp Glu Val Pro Ser Leu Phe Met Thr Asn Val Trp Thr

1070 1075 1080

Pro Pro Asn Pro Asn Thr Val Tyr His Cys Ser Ala Val Tyr Asn

1085 1090 1095

Asn Glu Phe Tyr Tyr Val Leu Cys Ala Val Ser Thr Val Gly Asp

1100 1105 1110

Pro Ile Leu Asn Ser Thr Tyr Trp Ser Gly Ser Leu Met Met Thr

1115 1120 1125

Arg Leu Ala Val Lys Pro Lys Ser Asn Gly Gly Gly Tyr Asn Gln

1130 1135 1140

His Gln Leu Ala Leu Arg Ser Ile Glu Lys Gly Arg Tyr Asp Lys

1145 1150 1155

Val Met Pro Tyr Gly Pro Ser Gly Ile Lys Gln Gly Asp Thr Leu

1160 1165 1170

Tyr Phe Pro Ala Val Gly Phe Leu Val Arg Thr Glu Phe Lys Tyr

1175 1180 1185

Asn Asp Ser Asn Cys Pro Ile Thr Lys Cys Gln Tyr Ser Lys Pro

1190 1195 1200

Glu Asn Cys Arg Leu Ser Met Gly Ile Arg Pro Asn Ser His Tyr

1205 1210 1215

Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn Leu Ser Asp Gly Glu

1220 1225 1230

Asn Pro Lys Val Val Phe Ile Glu Ile Ser Asp Gln Arg Leu Ser

1235 1240 1245

Ile Gly Ser Pro Ser Lys Ile Tyr Asp Ser Leu Gly Gln Pro Val

1250 1255 1260

Phe Tyr Gln Ala Ser Phe Ser Trp Asp Thr Met Ile Lys Phe Gly

1265 1270 1275

Asp Val Leu Thr Val Asn Pro Leu Val Val Asn Trp Arg Asn Asn

1280 1285 1290

Thr Val Ile Ser Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn

1295 1300 1305

Thr Cys Pro Glu Ile Cys Trp Glu Gly Val Tyr Asn Asp Ala Phe

1310 1315 1320

Leu Ile Asp Arg Ile Asn Trp Ile Ser Ala Gly Val Phe Leu Asp

1325 1330 1335

Ser Asn Gln Thr Ala Glu Asn Pro Val Phe Thr Val Phe Lys Asp

1340 1345 1350

Asn Glu Ile Leu Tyr Arg Ala Gln Leu Ala Ser Glu Asp Thr Asn

1355 1360 1365

Ala Gln Lys Thr Ile Thr Asn Cys Phe Leu Leu Lys Asn Lys Ile

1370 1375 1380

Trp Cys Ile Ser Leu Val Glu Ile Tyr Asp Thr Gly Asp Asn Val

1385 1390 1395

Ile Arg Pro Lys Leu Phe Ala Val Lys Ile Pro Glu Gln Cys Thr

1400 1405 1410

Gly Gly Leu Val Pro Arg Gly Ser His His His His His His Ser

1415 1420 1425

Ala Trp Ser His Pro Gln Phe Glu Lys

1430 1435

<210> 48

<211> 1855

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 48

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Gly Ile Leu His Tyr Glu Lys Leu Ser Lys Ile

20 25 30

Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro

35 40 45

Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn Val Ser Asn Met

50 55 60

Ser Gln Cys Thr Gly Ser Val Met Glu Asn Tyr Lys Thr Arg Leu Asn

65 70 75 80

Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile Tyr Lys Asn Gly

85 90 95

Gly Ser Gly Val Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile Thr Ala

100 105 110

Gly Val Ala Leu Tyr Glu Ala Met Lys Asn Ala Asp Asn Ile Asn Lys

115 120 125

Leu Lys Ser Ser Ile Glu Ser Thr Asn Glu Ala Val Val Lys Leu Gln

130 135 140

Glu Thr Ala Glu Lys Thr Val Tyr Val Leu Thr Ala Leu Gln Asp Tyr

145 150 155 160

Ile Asn Thr Asn Leu Val Pro Thr Ile Asp Lys Ile Ser Cys Lys Gln

165 170 175

Thr Glu Leu Ser Leu Asp Leu Ala Leu Ser Lys Tyr Leu Ser Asp Leu

180 185 190

Leu Phe Val Phe Gly Pro Asn Leu Gln Asp Pro Val Ser Asn Ser Met

195 200 205

Thr Ile Gln Ala Ile Ser Gln Ala Phe Gly Gly Asn Tyr Glu Thr Leu

210 215 220

Leu Arg Thr Leu Gly Tyr Ala Thr Glu Asp Phe Asp Asp Leu Leu Glu

225 230 235 240

Ser Asp Ser Ile Thr Gly Gln Ile Ile Tyr Val Asp Leu Ser Ser Tyr

245 250 255

Tyr Ile Ile Val Arg Val Tyr Phe Pro Ile Leu Thr Glu Ile Gln Gln

260 265 270

Ala Tyr Ile Gln Glu Leu Leu Pro Val Ser Phe Asn Asn Asp Asn Ser

275 280 285

Glu Trp Ile Ser Ile Val Pro Asn Phe Ile Leu Val Arg Asn Thr Leu

290 295 300

Ile Ser Asn Ile Glu Ile Gly Phe Cys Leu Ile Thr Lys Arg Ser Val

305 310 315 320

Ile Cys Asn Gln Asp Tyr Ala Thr Pro Met Thr Asn Asn Met Arg Glu

325 330 335

Cys Leu Thr Gly Ser Thr Glu Lys Cys Pro Arg Glu Leu Val Val Ser

340 345 350

Ser His Val Pro Arg Phe Ala Leu Ser Asn Gly Val Leu Phe Ala Asn

355 360 365

Cys Ile Ser Val Thr Cys Gln Cys Gln Thr Thr Gly Arg Ala Ile Ser

370 375 380

Gln Ser Gly Glu Gln Thr Leu Leu Met Ile Asp Asn Thr Thr Cys Pro

385 390 395 400

Thr Ala Val Leu Gly Asn Val Ile Ile Ser Leu Gly Lys Tyr Leu Gly

405 410 415

Ser Val Asn Tyr Asn Ser Glu Gly Ile Ala Ile Gly Pro Pro Val Phe

420 425 430

Thr Asp Lys Val Asp Ile Ser Ser Gln Ile Ser Ser Met Asn Gln Ser

435 440 445

Leu Gln Gln Ser Lys Asp Tyr Ile Lys Glu Ala Gln Arg Leu Leu Asp

450 455 460

Thr Val Asn Pro Ser Leu Lys Leu Met Lys Gln Ile Glu Asp Lys Ile

465 470 475 480

Glu Glu Ile Leu Ser Lys Ile Tyr His Ile Glu Asn Glu Ile Ala Arg

485 490 495

Ile Lys Lys Leu Ile Gly Glu Ala Pro Gly Ser Gly Tyr Ile Pro Glu

500 505 510

Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys Asp Gly Glu Trp Val

515 520 525

Leu Leu Ser Thr Phe Leu Gly Ser Gly Gly Gly Gly Gly Gly Val Ser

530 535 540

Asn Leu Val Gly Leu Pro Asn Asn Ile Cys Leu Gln Lys Thr Ser Asn

545 550 555 560

Gln Ile Leu Lys Pro Lys Leu Ile Ser Tyr Thr Leu Pro Val Val Gly

565 570 575

Gln Ser Gly Thr Cys Ile Thr Asp Pro Leu Leu Ala Met Asp Glu Gly

580 585 590

Tyr Phe Ala Tyr Ser His Leu Glu Arg Ile Gly Ser Cys Ser Arg Gly

595 600 605

Val Ser Lys Gln Arg Ile Ile Gly Val Gly Glu Val Leu Asp Arg Gly

610 615 620

Asp Glu Val Pro Ser Leu Phe Met Thr Asn Val Trp Thr Pro Pro Asn

625 630 635 640

Pro Asn Thr Val Tyr His Cys Ser Ala Val Tyr Asn Asn Glu Phe Tyr

645 650 655

Tyr Val Leu Cys Ala Val Ser Thr Val Gly Asp Pro Ile Leu Asn Ser

660 665 670

Thr Tyr Trp Ser Gly Ser Leu Met Met Thr Arg Leu Ala Val Lys Pro

675 680 685

Lys Ser Asn Gly Gly Gly Tyr Asn Gln His Gln Leu Ala Leu Arg Ser

690 695 700

Ile Glu Lys Gly Arg Tyr Asp Lys Val Met Pro Tyr Gly Pro Ser Gly

705 710 715 720

Ile Lys Gln Gly Asp Thr Leu Tyr Phe Pro Ala Val Gly Phe Leu Val

725 730 735

Arg Thr Glu Phe Lys Tyr Asn Asp Ser Asn Cys Pro Ile Thr Lys Cys

740 745 750

Gln Tyr Ser Lys Pro Glu Asn Cys Arg Leu Ser Met Gly Ile Arg Pro

755 760 765

Asn Ser His Tyr Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn Leu Ser

770 775 780

Asp Gly Glu Asn Pro Lys Val Val Phe Ile Glu Ile Ser Asp Gln Arg

785 790 795 800

Leu Ser Ile Gly Ser Pro Ser Lys Ile Tyr Asp Ser Leu Gly Gln Pro

805 810 815

Val Phe Tyr Gln Ala Ser Phe Ser Trp Asp Thr Met Ile Lys Phe Gly

820 825 830

Asp Val Leu Thr Val Asn Pro Leu Val Val Asn Trp Arg Asn Asn Thr

835 840 845

Val Ile Ser Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn Thr Cys

850 855 860

Pro Glu Ile Cys Trp Glu Gly Val Tyr Asn Asp Ala Phe Leu Ile Asp

865 870 875 880

Arg Ile Asn Trp Ile Ser Ala Gly Val Phe Leu Asp Ser Asn Gln Thr

885 890 895

Ala Glu Asn Pro Val Phe Thr Val Phe Lys Asp Asn Glu Ile Leu Tyr

900 905 910

Arg Ala Gln Leu Ala Ser Glu Asp Thr Asn Ala Gln Lys Thr Ile Thr

915 920 925

Asn Cys Phe Leu Leu Lys Asn Lys Ile Trp Cys Ile Ser Leu Val Glu

930 935 940

Ile Tyr Asp Thr Gly Asp Asn Val Ile Arg Pro Lys Leu Phe Ala Val

945 950 955 960

Lys Ile Pro Glu Gln Cys Thr Gly Gly Gly Gly Gly Gly Gly Val Ser

965 970 975

Asn Leu Val Gly Leu Pro Asn Asn Ile Cys Leu Gln Lys Thr Ser Asn

980 985 990

Gln Ile Leu Lys Pro Lys Leu Ile Ser Tyr Thr Leu Pro Val Val Gly

995 1000 1005

Gln Ser Gly Thr Cys Ile Thr Asp Pro Leu Leu Ala Met Asp Glu

1010 1015 1020

Gly Tyr Phe Ala Tyr Ser His Leu Glu Arg Ile Gly Ser Cys Ser

1025 1030 1035

Arg Gly Val Ser Lys Gln Arg Ile Ile Gly Val Gly Glu Val Leu

1040 1045 1050

Asp Arg Gly Asp Glu Val Pro Ser Leu Phe Met Thr Asn Val Trp

1055 1060 1065

Thr Pro Pro Asn Pro Asn Thr Val Tyr His Cys Ser Ala Val Tyr

1070 1075 1080

Asn Asn Glu Phe Tyr Tyr Val Leu Cys Ala Val Ser Thr Val Gly

1085 1090 1095

Asp Pro Ile Leu Asn Ser Thr Tyr Trp Ser Gly Ser Leu Met Met

1100 1105 1110

Thr Arg Leu Ala Val Lys Pro Lys Ser Asn Gly Gly Gly Tyr Asn

1115 1120 1125

Gln His Gln Leu Ala Leu Arg Ser Ile Glu Lys Gly Arg Tyr Asp

1130 1135 1140

Lys Val Met Pro Tyr Gly Pro Ser Gly Ile Lys Gln Gly Asp Thr

1145 1150 1155

Leu Tyr Phe Pro Ala Val Gly Phe Leu Val Arg Thr Glu Phe Lys

1160 1165 1170

Tyr Asn Asp Ser Asn Cys Pro Ile Thr Lys Cys Gln Tyr Ser Lys

1175 1180 1185

Pro Glu Asn Cys Arg Leu Ser Met Gly Ile Arg Pro Asn Ser His

1190 1195 1200

Tyr Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn Leu Ser Asp Gly

1205 1210 1215

Glu Asn Pro Lys Val Val Phe Ile Glu Ile Ser Asp Gln Arg Leu

1220 1225 1230

Ser Ile Gly Ser Pro Ser Lys Ile Tyr Asp Ser Leu Gly Gln Pro

1235 1240 1245

Val Phe Tyr Gln Ala Ser Phe Ser Trp Asp Thr Met Ile Lys Phe

1250 1255 1260

Gly Asp Val Leu Thr Val Asn Pro Leu Val Val Asn Trp Arg Asn

1265 1270 1275

Asn Thr Val Ile Ser Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe

1280 1285 1290

Asn Thr Cys Pro Glu Ile Cys Trp Glu Gly Val Tyr Asn Asp Ala

1295 1300 1305

Phe Leu Ile Asp Arg Ile Asn Trp Ile Ser Ala Gly Val Phe Leu

1310 1315 1320

Asp Ser Asn Gln Thr Ala Glu Asn Pro Val Phe Thr Val Phe Lys

1325 1330 1335

Asp Asn Glu Ile Leu Tyr Arg Ala Gln Leu Ala Ser Glu Asp Thr

1340 1345 1350

Asn Ala Gln Lys Thr Ile Thr Asn Cys Phe Leu Leu Lys Asn Lys

1355 1360 1365

Ile Trp Cys Ile Ser Leu Val Glu Ile Tyr Asp Thr Gly Asp Asn

1370 1375 1380

Val Ile Arg Pro Lys Leu Phe Ala Val Lys Ile Pro Glu Gln Cys

1385 1390 1395

Thr Gly Gly Gly Gly Gly Gly Gly Val Ser Asn Leu Val Gly Leu

1400 1405 1410

Pro Asn Asn Ile Cys Leu Gln Lys Thr Ser Asn Gln Ile Leu Lys

1415 1420 1425

Pro Lys Leu Ile Ser Tyr Thr Leu Pro Val Val Gly Gln Ser Gly

1430 1435 1440

Thr Cys Ile Thr Asp Pro Leu Leu Ala Met Asp Glu Gly Tyr Phe

1445 1450 1455

Ala Tyr Ser His Leu Glu Arg Ile Gly Ser Cys Ser Arg Gly Val

1460 1465 1470

Ser Lys Gln Arg Ile Ile Gly Val Gly Glu Val Leu Asp Arg Gly

1475 1480 1485

Asp Glu Val Pro Ser Leu Phe Met Thr Asn Val Trp Thr Pro Pro

1490 1495 1500

Asn Pro Asn Thr Val Tyr His Cys Ser Ala Val Tyr Asn Asn Glu

1505 1510 1515

Phe Tyr Tyr Val Leu Cys Ala Val Ser Thr Val Gly Asp Pro Ile

1520 1525 1530

Leu Asn Ser Thr Tyr Trp Ser Gly Ser Leu Met Met Thr Arg Leu

1535 1540 1545

Ala Val Lys Pro Lys Ser Asn Gly Gly Gly Tyr Asn Gln His Gln

1550 1555 1560

Leu Ala Leu Arg Ser Ile Glu Lys Gly Arg Tyr Asp Lys Val Met

1565 1570 1575

Pro Tyr Gly Pro Ser Gly Ile Lys Gln Gly Asp Thr Leu Tyr Phe

1580 1585 1590

Pro Ala Val Gly Phe Leu Val Arg Thr Glu Phe Lys Tyr Asn Asp

1595 1600 1605

Ser Asn Cys Pro Ile Thr Lys Cys Gln Tyr Ser Lys Pro Glu Asn

1610 1615 1620

Cys Arg Leu Ser Met Gly Ile Arg Pro Asn Ser His Tyr Ile Leu

1625 1630 1635

Arg Ser Gly Leu Leu Lys Tyr Asn Leu Ser Asp Gly Glu Asn Pro

1640 1645 1650

Lys Val Val Phe Ile Glu Ile Ser Asp Gln Arg Leu Ser Ile Gly

1655 1660 1665

Ser Pro Ser Lys Ile Tyr Asp Ser Leu Gly Gln Pro Val Phe Tyr

1670 1675 1680

Gln Ala Ser Phe Ser Trp Asp Thr Met Ile Lys Phe Gly Asp Val

1685 1690 1695

Leu Thr Val Asn Pro Leu Val Val Asn Trp Arg Asn Asn Thr Val

1700 1705 1710

Ile Ser Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn Thr Cys

1715 1720 1725

Pro Glu Ile Cys Trp Glu Gly Val Tyr Asn Asp Ala Phe Leu Ile

1730 1735 1740

Asp Arg Ile Asn Trp Ile Ser Ala Gly Val Phe Leu Asp Ser Asn

1745 1750 1755

Gln Thr Ala Glu Asn Pro Val Phe Thr Val Phe Lys Asp Asn Glu

1760 1765 1770

Ile Leu Tyr Arg Ala Gln Leu Ala Ser Glu Asp Thr Asn Ala Gln

1775 1780 1785

Lys Thr Ile Thr Asn Cys Phe Leu Leu Lys Asn Lys Ile Trp Cys

1790 1795 1800

Ile Ser Leu Val Glu Ile Tyr Asp Thr Gly Asp Asn Val Ile Arg

1805 1810 1815

Pro Lys Leu Phe Ala Val Lys Ile Pro Glu Gln Cys Thr Gly Gly

1820 1825 1830

Leu Val Pro Arg Gly Ser His His His His His His Ser Ala Trp

1835 1840 1845

Ser His Pro Gln Phe Glu Lys

1850 1855

<210> 49

<211> 1869

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 49

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Gly Ile Leu His Tyr Glu Lys Leu Ser Lys Ile

20 25 30

Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro

35 40 45

Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn Val Ser Asn Met

50 55 60

Ser Gln Cys Thr Gly Ser Val Met Glu Asn Tyr Lys Thr Arg Leu Asn

65 70 75 80

Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile Tyr Lys Asn Asn

85 90 95

Thr His Asp Cys Val Gly Asp Val Arg Leu Ala Gly Val Cys Met Ala

100 105 110

Gly Val Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile Thr Ala Gly Val

115 120 125

Ala Leu Tyr Glu Ala Met Lys Asn Ala Asp Asn Ile Asn Lys Leu Lys

130 135 140

Ser Ser Ile Glu Ser Thr Asn Glu Ala Val Val Lys Leu Gln Glu Thr

145 150 155 160

Ala Glu Lys Thr Val Tyr Val Phe Thr Ala Leu Gln Asp Tyr Ile Asn

165 170 175

Thr Asn Leu Val Pro Thr Ile Asp Lys Ile Pro Cys Lys Gln Thr Glu

180 185 190

Leu Ser Leu Asp Leu Ala Leu Ser Lys Tyr Leu Ser Asp Leu Leu Phe

195 200 205

Val Phe Gly Pro Asn Leu Gln Asp Pro Val Ser Asn Ser Met Thr Ile

210 215 220

Gln Ala Ile Ser Gln Ala Phe Gly Gly Asn Tyr Glu Thr Leu Leu Arg

225 230 235 240

Thr Leu Gly Tyr Ala Thr Glu Asp Phe Asp Asp Leu Leu Glu Ser Asp

245 250 255

Ser Ile Thr Gly Gln Ile Ile Tyr Val Asp Leu Ser Ser Tyr Tyr Ile

260 265 270

Ile Val Arg Val Tyr Phe Pro Ile Leu Thr Glu Ile Gln Gln Ala Tyr

275 280 285

Ile Gln Glu Leu Leu Pro Val Ser Phe Asn Asn Asp Asn Ser Glu Trp

290 295 300

Ile Ser Ile Val Pro Asn Phe Ile Leu Val Arg Asn Thr Leu Ile Ser

305 310 315 320

Asn Ile Glu Ile Gly Phe Cys Leu Ile Thr Lys Arg Ser Val Ile Cys

325 330 335

Asn Gln Asp Tyr Ala Thr Pro Met Thr Asn Asn Met Arg Glu Cys Leu

340 345 350

Thr Gly Ser Thr Glu Lys Cys Pro Arg Glu Leu Val Val Ser Ser His

355 360 365

Val Pro Arg Phe Ala Leu Ser Asn Gly Val Leu Phe Ala Asn Cys Ile

370 375 380

Ser Val Thr Cys Gln Cys Gln Thr Thr Gly Arg Ala Ile Ser Gln Ser

385 390 395 400

Gly Glu Gln Thr Leu Leu Met Ile Asp Asn Thr Thr Cys Pro Thr Ala

405 410 415

Val Leu Gly Asn Val Ile Ile Ser Leu Gly Lys Tyr Leu Gly Ser Val

420 425 430

Asn Tyr Asn Ser Glu Gly Ile Ala Ile Gly Pro Pro Val Phe Thr Asp

435 440 445

Lys Val Asp Ile Ser Ser Gln Ile Ser Ser Met Asn Gln Ser Leu Gln

450 455 460

Gln Ser Lys Asp Tyr Ile Lys Glu Ala Gln Arg Leu Leu Asp Thr Val

465 470 475 480

Asn Pro Ser Leu Lys Leu Met Lys Gln Ile Glu Asp Lys Ile Glu Glu

485 490 495

Ile Leu Ser Lys Ile Tyr His Ile Glu Asn Glu Ile Ala Arg Ile Lys

500 505 510

Lys Leu Ile Gly Glu Ala Pro Gly Ser Gly Tyr Ile Pro Glu Ala Pro

515 520 525

Arg Asp Gly Gln Ala Tyr Val Arg Lys Asp Gly Glu Trp Val Leu Leu

530 535 540

Ser Thr Phe Leu Gly Ser Gly Gly Gly Gly Gly Gly Val Ser Asn Leu

545 550 555 560

Val Gly Leu Pro Asn Asn Ile Cys Leu Gln Lys Thr Ser Asn Gln Ile

565 570 575

Leu Lys Pro Lys Leu Ile Ser Tyr Thr Leu Pro Val Val Gly Gln Ser

580 585 590

Gly Thr Cys Ile Thr Asp Pro Leu Leu Ala Met Asp Glu Gly Tyr Phe

595 600 605

Ala Tyr Ser His Leu Glu Arg Ile Gly Ser Cys Ser Arg Gly Val Ser

610 615 620

Lys Gln Arg Ile Ile Gly Val Gly Glu Val Leu Asp Arg Gly Asp Glu

625 630 635 640

Val Pro Ser Leu Phe Met Thr Asn Val Trp Thr Pro Pro Asn Pro Asn

645 650 655

Thr Val Tyr His Cys Ser Ala Val Tyr Asn Asn Glu Phe Tyr Tyr Val

660 665 670

Leu Cys Ala Val Ser Thr Val Gly Asp Pro Ile Leu Asn Ser Thr Tyr

675 680 685

Trp Ser Gly Ser Leu Met Met Thr Arg Leu Ala Val Lys Pro Lys Ser

690 695 700

Asn Gly Gly Gly Tyr Asn Gln His Gln Leu Ala Leu Arg Ser Ile Glu

705 710 715 720

Lys Gly Arg Tyr Asp Lys Val Met Pro Tyr Gly Pro Ser Gly Ile Lys

725 730 735

Gln Gly Asp Thr Leu Tyr Phe Pro Ala Val Gly Phe Leu Val Arg Thr

740 745 750

Glu Phe Lys Tyr Asn Asp Ser Asn Cys Pro Ile Thr Lys Cys Gln Tyr

755 760 765

Ser Lys Pro Glu Asn Cys Arg Leu Ser Met Gly Ile Arg Pro Asn Ser

770 775 780

His Tyr Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn Leu Ser Asp Gly

785 790 795 800

Glu Asn Pro Lys Val Val Phe Ile Glu Ile Ser Asp Gln Arg Leu Ser

805 810 815

Ile Gly Ser Pro Ser Lys Ile Tyr Asp Ser Leu Gly Gln Pro Val Phe

820 825 830

Tyr Gln Ala Ser Phe Ser Trp Asp Thr Met Ile Lys Phe Gly Asp Val

835 840 845

Leu Thr Val Asn Pro Leu Val Val Asn Trp Arg Asn Asn Thr Val Ile

850 855 860

Ser Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn Thr Cys Pro Glu

865 870 875 880

Ile Cys Trp Glu Gly Val Tyr Asn Asp Ala Phe Leu Ile Asp Arg Ile

885 890 895

Asn Trp Ile Ser Ala Gly Val Phe Leu Asp Ser Asn Gln Thr Ala Glu

900 905 910

Asn Pro Val Phe Thr Val Phe Lys Asp Asn Glu Ile Leu Tyr Arg Ala

915 920 925

Gln Leu Ala Ser Glu Asp Thr Asn Ala Gln Lys Thr Ile Thr Asn Cys

930 935 940

Phe Leu Leu Lys Asn Lys Ile Trp Cys Ile Ser Leu Val Glu Ile Tyr

945 950 955 960

Asp Thr Gly Asp Asn Val Ile Arg Pro Lys Leu Phe Ala Val Lys Ile

965 970 975

Pro Glu Gln Cys Thr Gly Gly Gly Gly Gly Gly Gly Val Ser Asn Leu

980 985 990

Val Gly Leu Pro Asn Asn Ile Cys Leu Gln Lys Thr Ser Asn Gln Ile

995 1000 1005

Leu Lys Pro Lys Leu Ile Ser Tyr Thr Leu Pro Val Val Gly Gln

1010 1015 1020

Ser Gly Thr Cys Ile Thr Asp Pro Leu Leu Ala Met Asp Glu Gly

1025 1030 1035

Tyr Phe Ala Tyr Ser His Leu Glu Arg Ile Gly Ser Cys Ser Arg

1040 1045 1050

Gly Val Ser Lys Gln Arg Ile Ile Gly Val Gly Glu Val Leu Asp

1055 1060 1065

Arg Gly Asp Glu Val Pro Ser Leu Phe Met Thr Asn Val Trp Thr

1070 1075 1080

Pro Pro Asn Pro Asn Thr Val Tyr His Cys Ser Ala Val Tyr Asn

1085 1090 1095

Asn Glu Phe Tyr Tyr Val Leu Cys Ala Val Ser Thr Val Gly Asp

1100 1105 1110

Pro Ile Leu Asn Ser Thr Tyr Trp Ser Gly Ser Leu Met Met Thr

1115 1120 1125

Arg Leu Ala Val Lys Pro Lys Ser Asn Gly Gly Gly Tyr Asn Gln

1130 1135 1140

His Gln Leu Ala Leu Arg Ser Ile Glu Lys Gly Arg Tyr Asp Lys

1145 1150 1155

Val Met Pro Tyr Gly Pro Ser Gly Ile Lys Gln Gly Asp Thr Leu

1160 1165 1170

Tyr Phe Pro Ala Val Gly Phe Leu Val Arg Thr Glu Phe Lys Tyr

1175 1180 1185

Asn Asp Ser Asn Cys Pro Ile Thr Lys Cys Gln Tyr Ser Lys Pro

1190 1195 1200

Glu Asn Cys Arg Leu Ser Met Gly Ile Arg Pro Asn Ser His Tyr

1205 1210 1215

Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn Leu Ser Asp Gly Glu

1220 1225 1230

Asn Pro Lys Val Val Phe Ile Glu Ile Ser Asp Gln Arg Leu Ser

1235 1240 1245

Ile Gly Ser Pro Ser Lys Ile Tyr Asp Ser Leu Gly Gln Pro Val

1250 1255 1260

Phe Tyr Gln Ala Ser Phe Ser Trp Asp Thr Met Ile Lys Phe Gly

1265 1270 1275

Asp Val Leu Thr Val Asn Pro Leu Val Val Asn Trp Arg Asn Asn

1280 1285 1290

Thr Val Ile Ser Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn

1295 1300 1305

Thr Cys Pro Glu Ile Cys Trp Glu Gly Val Tyr Asn Asp Ala Phe

1310 1315 1320

Leu Ile Asp Arg Ile Asn Trp Ile Ser Ala Gly Val Phe Leu Asp

1325 1330 1335

Ser Asn Gln Thr Ala Glu Asn Pro Val Phe Thr Val Phe Lys Asp

1340 1345 1350

Asn Glu Ile Leu Tyr Arg Ala Gln Leu Ala Ser Glu Asp Thr Asn

1355 1360 1365

Ala Gln Lys Thr Ile Thr Asn Cys Phe Leu Leu Lys Asn Lys Ile

1370 1375 1380

Trp Cys Ile Ser Leu Val Glu Ile Tyr Asp Thr Gly Asp Asn Val

1385 1390 1395

Ile Arg Pro Lys Leu Phe Ala Val Lys Ile Pro Glu Gln Cys Thr

1400 1405 1410

Gly Gly Gly Gly Gly Gly Gly Val Ser Asn Leu Val Gly Leu Pro

1415 1420 1425

Asn Asn Ile Cys Leu Gln Lys Thr Ser Asn Gln Ile Leu Lys Pro

1430 1435 1440

Lys Leu Ile Ser Tyr Thr Leu Pro Val Val Gly Gln Ser Gly Thr

1445 1450 1455

Cys Ile Thr Asp Pro Leu Leu Ala Met Asp Glu Gly Tyr Phe Ala

1460 1465 1470

Tyr Ser His Leu Glu Arg Ile Gly Ser Cys Ser Arg Gly Val Ser

1475 1480 1485

Lys Gln Arg Ile Ile Gly Val Gly Glu Val Leu Asp Arg Gly Asp

1490 1495 1500

Glu Val Pro Ser Leu Phe Met Thr Asn Val Trp Thr Pro Pro Asn

1505 1510 1515

Pro Asn Thr Val Tyr His Cys Ser Ala Val Tyr Asn Asn Glu Phe

1520 1525 1530

Tyr Tyr Val Leu Cys Ala Val Ser Thr Val Gly Asp Pro Ile Leu

1535 1540 1545

Asn Ser Thr Tyr Trp Ser Gly Ser Leu Met Met Thr Arg Leu Ala

1550 1555 1560

Val Lys Pro Lys Ser Asn Gly Gly Gly Tyr Asn Gln His Gln Leu

1565 1570 1575

Ala Leu Arg Ser Ile Glu Lys Gly Arg Tyr Asp Lys Val Met Pro

1580 1585 1590

Tyr Gly Pro Ser Gly Ile Lys Gln Gly Asp Thr Leu Tyr Phe Pro

1595 1600 1605

Ala Val Gly Phe Leu Val Arg Thr Glu Phe Lys Tyr Asn Asp Ser

1610 1615 1620

Asn Cys Pro Ile Thr Lys Cys Gln Tyr Ser Lys Pro Glu Asn Cys

1625 1630 1635

Arg Leu Ser Met Gly Ile Arg Pro Asn Ser His Tyr Ile Leu Arg

1640 1645 1650

Ser Gly Leu Leu Lys Tyr Asn Leu Ser Asp Gly Glu Asn Pro Lys

1655 1660 1665

Val Val Phe Ile Glu Ile Ser Asp Gln Arg Leu Ser Ile Gly Ser

1670 1675 1680

Pro Ser Lys Ile Tyr Asp Ser Leu Gly Gln Pro Val Phe Tyr Gln

1685 1690 1695

Ala Ser Phe Ser Trp Asp Thr Met Ile Lys Phe Gly Asp Val Leu

1700 1705 1710

Thr Val Asn Pro Leu Val Val Asn Trp Arg Asn Asn Thr Val Ile

1715 1720 1725

Ser Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn Thr Cys Pro

1730 1735 1740

Glu Ile Cys Trp Glu Gly Val Tyr Asn Asp Ala Phe Leu Ile Asp

1745 1750 1755

Arg Ile Asn Trp Ile Ser Ala Gly Val Phe Leu Asp Ser Asn Gln

1760 1765 1770

Thr Ala Glu Asn Pro Val Phe Thr Val Phe Lys Asp Asn Glu Ile

1775 1780 1785

Leu Tyr Arg Ala Gln Leu Ala Ser Glu Asp Thr Asn Ala Gln Lys

1790 1795 1800

Thr Ile Thr Asn Cys Phe Leu Leu Lys Asn Lys Ile Trp Cys Ile

1805 1810 1815

Ser Leu Val Glu Ile Tyr Asp Thr Gly Asp Asn Val Ile Arg Pro

1820 1825 1830

Lys Leu Phe Ala Val Lys Ile Pro Glu Gln Cys Thr Gly Gly Leu

1835 1840 1845

Val Pro Arg Gly Ser His His His His His His Ser Ala Trp Ser

1850 1855 1860

His Pro Gln Phe Glu Lys

1865

<210> 50

<211> 966

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 50

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Arg Pro Gln Thr Glu Gly Val Ser Asn Leu Val

20 25 30

Gly Leu Pro Asn Asn Ile Cys Leu Gln Lys Thr Ser Asn Gln Ile Leu

35 40 45

Lys Pro Lys Leu Ile Ser Tyr Thr Leu Pro Val Val Gly Gln Ser Gly

50 55 60

Thr Cys Ile Thr Asp Pro Leu Leu Ala Met Asp Glu Gly Tyr Phe Ala

65 70 75 80

Tyr Ser His Leu Glu Arg Ile Gly Ser Cys Ser Arg Gly Val Ser Lys

85 90 95

Gln Arg Ile Ile Gly Val Gly Glu Val Leu Asp Arg Gly Asp Glu Val

100 105 110

Pro Ser Leu Phe Met Thr Asn Val Trp Thr Pro Pro Asn Pro Asn Thr

115 120 125

Val Tyr His Cys Ser Ala Val Tyr Asn Asn Glu Phe Tyr Tyr Val Leu

130 135 140

Cys Ala Val Ser Thr Val Gly Asp Pro Ile Leu Asn Ser Thr Tyr Trp

145 150 155 160

Ser Gly Ser Leu Met Met Thr Arg Leu Ala Val Lys Pro Lys Ser Asn

165 170 175

Gly Gly Gly Tyr Asn Gln His Gln Leu Ala Leu Arg Ser Ile Glu Lys

180 185 190

Gly Arg Tyr Asp Lys Val Met Pro Tyr Gly Pro Ser Gly Ile Lys Gln

195 200 205

Gly Asp Thr Leu Tyr Phe Pro Ala Val Gly Phe Leu Val Arg Thr Glu

210 215 220

Phe Lys Tyr Asn Asp Ser Asn Cys Pro Ile Thr Lys Cys Gln Tyr Ser

225 230 235 240

Lys Pro Glu Asn Cys Arg Leu Ser Met Gly Ile Arg Pro Asn Ser His

245 250 255

Tyr Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn Leu Ser Asp Gly Glu

260 265 270

Asn Pro Lys Val Val Phe Ile Glu Ile Ser Asp Gln Arg Leu Ser Ile

275 280 285

Gly Ser Pro Ser Lys Ile Tyr Asp Ser Leu Gly Gln Pro Val Phe Tyr

290 295 300

Gln Ala Ser Phe Ser Trp Asp Thr Met Ile Lys Phe Gly Asp Val Leu

305 310 315 320

Thr Val Asn Pro Leu Val Val Asn Trp Arg Asn Asn Thr Val Ile Ser

325 330 335

Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn Thr Cys Pro Glu Ile

340 345 350

Cys Trp Glu Gly Val Tyr Asn Asp Ala Phe Leu Ile Asp Arg Ile Asn

355 360 365

Trp Ile Ser Ala Gly Val Phe Leu Asp Ser Asn Gln Thr Ala Glu Asn

370 375 380

Pro Val Phe Thr Val Phe Lys Asp Asn Glu Ile Leu Tyr Arg Ala Gln

385 390 395 400

Leu Ala Ser Glu Asp Thr Asn Ala Gln Lys Thr Ile Thr Asn Cys Phe

405 410 415

Leu Leu Lys Asn Lys Ile Trp Cys Ile Ser Leu Val Glu Ile Tyr Asp

420 425 430

Thr Gly Asp Asn Val Ile Arg Pro Lys Leu Phe Ala Val Lys Ile Pro

435 440 445

Glu Gln Cys Thr Gly Gly Gly Gly Gly Gln Gly Ile Leu His Tyr Glu

450 455 460

Lys Leu Ser Lys Ile Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys

465 470 475 480

Ile Lys Ser Asn Pro Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro

485 490 495

Asn Val Ser Asn Met Ser Gln Cys Thr Gly Ser Val Met Glu Asn Tyr

500 505 510

Lys Thr Arg Leu Asn Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu

515 520 525

Ile Tyr Lys Asn Gly Gly Ser Gly Val Ala Ile Gly Ile Ala Thr Ala

530 535 540

Ala Gln Ile Thr Ala Gly Val Ala Leu Tyr Glu Ala Met Lys Asn Ala

545 550 555 560

Asp Asn Ile Asn Lys Leu Lys Ser Ser Ile Glu Ser Thr Asn Glu Ala

565 570 575

Val Val Lys Leu Gln Glu Thr Ala Glu Lys Thr Val Tyr Val Leu Thr

580 585 590

Ala Leu Gln Asp Tyr Ile Asn Thr Asn Leu Val Pro Thr Ile Asp Lys

595 600 605

Ile Ser Cys Lys Gln Thr Glu Leu Ser Leu Asp Leu Ala Leu Ser Lys

610 615 620

Tyr Leu Ser Asp Leu Leu Phe Val Phe Gly Pro Asn Leu Gln Asp Pro

625 630 635 640

Val Ser Asn Ser Met Thr Ile Gln Ala Ile Ser Gln Ala Phe Gly Gly

645 650 655

Asn Tyr Glu Thr Leu Leu Arg Thr Leu Gly Tyr Ala Thr Glu Asp Phe

660 665 670

Asp Asp Leu Leu Glu Ser Asp Ser Ile Thr Gly Gln Ile Ile Tyr Val

675 680 685

Asp Leu Ser Ser Tyr Tyr Ile Ile Val Arg Val Tyr Phe Pro Ile Leu

690 695 700

Thr Glu Ile Gln Gln Ala Tyr Ile Gln Glu Leu Leu Pro Val Ser Phe

705 710 715 720

Asn Asn Asp Asn Ser Glu Trp Ile Ser Ile Val Pro Asn Phe Ile Leu

725 730 735

Val Arg Asn Thr Leu Ile Ser Asn Ile Glu Ile Gly Phe Cys Leu Ile

740 745 750

Thr Lys Arg Ser Val Ile Cys Asn Gln Asp Tyr Ala Thr Pro Met Thr

755 760 765

Asn Asn Met Arg Glu Cys Leu Thr Gly Ser Thr Glu Lys Cys Pro Arg

770 775 780

Glu Leu Val Val Ser Ser His Val Pro Arg Phe Ala Leu Ser Asn Gly

785 790 795 800

Val Leu Phe Ala Asn Cys Ile Ser Val Thr Cys Gln Cys Gln Thr Thr

805 810 815

Gly Arg Ala Ile Ser Gln Ser Gly Glu Gln Thr Leu Leu Met Ile Asp

820 825 830

Asn Thr Thr Cys Pro Thr Ala Val Leu Gly Asn Val Ile Ile Ser Leu

835 840 845

Gly Lys Tyr Leu Gly Ser Val Asn Tyr Asn Ser Glu Gly Ile Ala Ile

850 855 860

Gly Pro Pro Val Phe Thr Asp Lys Val Asp Ile Ser Ser Gln Ile Ser

865 870 875 880

Ser Met Asn Gln Ser Leu Gln Gln Ser Lys Asp Tyr Ile Lys Glu Ala

885 890 895

Gln Arg Leu Leu Asp Thr Val Asn Pro Ser Leu Lys Leu Met Lys Gln

900 905 910

Ile Glu Asp Lys Ile Glu Glu Ile Leu Ser Lys Ile Tyr His Ile Glu

915 920 925

Asn Glu Ile Ala Arg Ile Lys Lys Leu Ile Gly Glu Ala Pro Gly Gly

930 935 940

Leu Val Pro Arg Gly Ser His His His His His His Ser Ala Trp Ser

945 950 955 960

His Pro Gln Phe Glu Lys

965

<210> 51

<211> 1013

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 51

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Arg Pro Gln Thr Glu Gly Val Ser Asn Leu Val

20 25 30

Gly Leu Pro Asn Asn Ile Cys Leu Gln Lys Thr Ser Asn Gln Ile Leu

35 40 45

Lys Pro Lys Leu Ile Ser Tyr Thr Leu Pro Val Val Gly Gln Ser Gly

50 55 60

Thr Cys Ile Thr Asp Pro Leu Leu Ala Met Asp Glu Gly Tyr Phe Ala

65 70 75 80

Tyr Ser His Leu Glu Arg Ile Gly Ser Cys Ser Arg Gly Val Ser Lys

85 90 95

Gln Arg Ile Ile Gly Val Gly Glu Val Leu Asp Arg Gly Asp Glu Val

100 105 110

Pro Ser Leu Phe Met Thr Asn Val Trp Thr Pro Pro Asn Pro Asn Thr

115 120 125

Val Tyr His Cys Ser Ala Val Tyr Asn Asn Glu Phe Tyr Tyr Val Leu

130 135 140

Cys Ala Val Ser Thr Val Gly Asp Pro Ile Leu Asn Ser Thr Tyr Trp

145 150 155 160

Ser Gly Ser Leu Met Met Thr Arg Leu Ala Val Lys Pro Lys Ser Asn

165 170 175

Gly Gly Gly Tyr Asn Gln His Gln Leu Ala Leu Arg Ser Ile Glu Lys

180 185 190

Gly Arg Tyr Asp Lys Val Met Pro Tyr Gly Pro Ser Gly Ile Lys Gln

195 200 205

Gly Asp Thr Leu Tyr Phe Pro Ala Val Gly Phe Leu Val Arg Thr Glu

210 215 220

Phe Lys Tyr Asn Asp Ser Asn Cys Pro Ile Thr Lys Cys Gln Tyr Ser

225 230 235 240

Lys Pro Glu Asn Cys Arg Leu Ser Met Gly Ile Arg Pro Asn Ser His

245 250 255

Tyr Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn Leu Ser Asp Gly Glu

260 265 270

Asn Pro Lys Val Val Phe Ile Glu Ile Ser Asp Gln Arg Leu Ser Ile

275 280 285

Gly Ser Pro Ser Lys Ile Tyr Asp Ser Leu Gly Gln Pro Val Phe Tyr

290 295 300

Gln Ala Ser Phe Ser Trp Asp Thr Met Ile Lys Phe Gly Asp Val Leu

305 310 315 320

Thr Val Asn Pro Leu Val Val Asn Trp Arg Asn Asn Thr Val Ile Ser

325 330 335

Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn Thr Cys Pro Glu Ile

340 345 350

Cys Trp Glu Gly Val Tyr Asn Asp Ala Phe Leu Ile Asp Arg Ile Asn

355 360 365

Trp Ile Ser Ala Gly Val Phe Leu Asp Ser Asn Gln Thr Ala Glu Asn

370 375 380

Pro Val Phe Thr Val Phe Lys Asp Asn Glu Ile Leu Tyr Arg Ala Gln

385 390 395 400

Leu Ala Ser Glu Asp Thr Asn Ala Gln Lys Thr Ile Thr Asn Cys Phe

405 410 415

Leu Leu Lys Asn Lys Ile Trp Cys Ile Ser Leu Val Glu Ile Tyr Asp

420 425 430

Thr Gly Asp Asn Val Ile Arg Pro Lys Leu Phe Ala Val Lys Ile Pro

435 440 445

Glu Gln Cys Thr Gly Gly Gly Gly Ser Gly Gly Gly Gly Gln Gly Ile

450 455 460

Leu His Tyr Glu Lys Leu Ser Lys Ile Gly Leu Val Lys Gly Val Thr

465 470 475 480

Arg Lys Tyr Lys Ile Lys Ser Asn Pro Leu Thr Lys Asp Ile Val Ile

485 490 495

Lys Met Ile Pro Asn Val Ser Asn Met Ser Gln Cys Thr Gly Ser Val

500 505 510

Met Glu Asn Tyr Lys Thr Arg Leu Asn Gly Ile Leu Thr Pro Ile Lys

515 520 525

Gly Ala Leu Glu Ile Tyr Lys Asn Asn Thr His Asp Cys Val Gly Asp

530 535 540

Val Arg Leu Ala Gly Val Cys Met Ala Gly Val Ala Ile Gly Ile Ala

545 550 555 560

Thr Ala Ala Gln Ile Thr Ala Gly Val Ala Leu Tyr Glu Ala Met Lys

565 570 575

Asn Ala Asp Asn Ile Asn Lys Leu Lys Ser Ser Ile Glu Ser Thr Asn

580 585 590

Glu Ala Val Val Lys Leu Gln Glu Thr Ala Glu Lys Thr Val Tyr Val

595 600 605

Phe Thr Ala Leu Gln Asp Tyr Ile Asn Thr Asn Leu Val Pro Thr Ile

610 615 620

Asp Lys Ile Pro Cys Lys Gln Thr Glu Leu Ser Leu Asp Leu Ala Leu

625 630 635 640

Ser Lys Tyr Leu Ser Asp Leu Leu Phe Val Phe Gly Pro Asn Leu Gln

645 650 655

Asp Pro Val Ser Asn Ser Met Thr Ile Gln Ala Ile Ser Gln Ala Phe

660 665 670

Gly Gly Asn Tyr Glu Thr Leu Leu Arg Thr Leu Gly Tyr Ala Thr Glu

675 680 685

Asp Phe Asp Asp Leu Leu Glu Ser Asp Ser Ile Thr Gly Gln Ile Ile

690 695 700

Tyr Val Asp Leu Ser Ser Tyr Tyr Ile Ile Val Arg Val Tyr Phe Pro

705 710 715 720

Ile Leu Thr Glu Ile Gln Gln Ala Tyr Ile Gln Glu Leu Leu Pro Val

725 730 735

Ser Phe Asn Asn Asp Asn Ser Glu Trp Ile Ser Ile Val Pro Asn Phe

740 745 750

Ile Leu Val Arg Asn Thr Leu Ile Ser Asn Ile Glu Ile Gly Phe Cys

755 760 765

Leu Ile Thr Lys Arg Ser Val Ile Cys Asn Gln Asp Tyr Ala Thr Pro

770 775 780

Met Thr Asn Asn Met Arg Glu Cys Leu Thr Gly Ser Thr Glu Lys Cys

785 790 795 800

Pro Arg Glu Leu Val Val Ser Ser His Val Pro Arg Phe Ala Leu Ser

805 810 815

Asn Gly Val Leu Phe Ala Asn Cys Ile Ser Val Thr Cys Gln Cys Gln

820 825 830

Thr Thr Gly Arg Ala Ile Ser Gln Ser Gly Glu Gln Thr Leu Leu Met

835 840 845

Ile Asp Asn Thr Thr Cys Pro Thr Ala Val Leu Gly Asn Val Ile Ile

850 855 860

Ser Leu Gly Lys Tyr Leu Gly Ser Val Asn Tyr Asn Ser Glu Gly Ile

865 870 875 880

Ala Ile Gly Pro Pro Val Phe Thr Asp Lys Val Asp Ile Ser Ser Gln

885 890 895

Ile Ser Ser Met Asn Gln Ser Leu Gln Gln Ser Lys Asp Tyr Ile Lys

900 905 910

Glu Ala Gln Arg Leu Leu Asp Thr Val Asn Pro Ser Leu Lys Leu Met

915 920 925

Lys Gln Ile Glu Asp Lys Ile Glu Glu Ile Leu Ser Lys Ile Tyr His

930 935 940

Ile Glu Asn Glu Ile Ala Arg Ile Lys Lys Leu Ile Gly Glu Ala Pro

945 950 955 960

Gly Ser Gly Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln Ala Tyr Val

965 970 975

Arg Lys Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu Gly Ser Leu

980 985 990

Val Pro Arg Gly Ser His His His His His His Ser Ala Trp Ser His

995 1000 1005

Pro Gln Phe Glu Lys

1010

<210> 52

<211> 546

<212> PRT

<213> 尼帕病毒

<400> 52

Met Val Val Ile Leu Asp Lys Arg Cys Tyr Cys Asn Leu Leu Ile Leu

1 5 10 15

Ile Leu Met Ile Ser Glu Cys Ser Val Gly Ile Leu His Tyr Glu Lys

20 25 30

Leu Ser Lys Ile Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile

35 40 45

Lys Ser Asn Pro Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn

50 55 60

Val Ser Asn Met Ser Gln Cys Thr Gly Ser Val Met Glu Asn Tyr Lys

65 70 75 80

Thr Arg Leu Asn Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile

85 90 95

Tyr Lys Asn Asn Thr His Asp Leu Val Gly Asp Val Arg Leu Ala Gly

100 105 110

Val Ile Met Ala Gly Val Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile

115 120 125

Thr Ala Gly Val Ala Leu Tyr Glu Ala Met Lys Asn Ala Asp Asn Ile

130 135 140

Asn Lys Leu Lys Ser Ser Ile Glu Ser Thr Asn Glu Ala Val Val Lys

145 150 155 160

Leu Gln Glu Thr Ala Glu Lys Thr Val Tyr Val Leu Thr Ala Leu Gln

165 170 175

Asp Tyr Ile Asn Thr Asn Leu Val Pro Thr Ile Asp Lys Ile Ser Cys

180 185 190

Lys Gln Thr Glu Leu Ser Leu Asp Leu Ala Leu Ser Lys Tyr Leu Ser

195 200 205

Asp Leu Leu Phe Val Phe Gly Pro Asn Leu Gln Asp Pro Val Ser Asn

210 215 220

Ser Met Thr Ile Gln Ala Ile Ser Gln Ala Phe Gly Gly Asn Tyr Glu

225 230 235 240

Thr Leu Leu Arg Thr Leu Gly Tyr Ala Thr Glu Asp Phe Asp Asp Leu

245 250 255

Leu Glu Ser Asp Ser Ile Thr Gly Gln Ile Ile Tyr Val Asp Leu Ser

260 265 270

Ser Tyr Tyr Ile Ile Val Arg Val Tyr Phe Pro Ile Leu Thr Glu Ile

275 280 285

Gln Gln Ala Tyr Ile Gln Glu Leu Leu Pro Val Ser Phe Asn Asn Asp

290 295 300

Asn Ser Glu Trp Ile Ser Ile Val Pro Asn Phe Ile Leu Val Arg Asn

305 310 315 320

Thr Leu Ile Ser Asn Ile Glu Ile Gly Phe Cys Leu Ile Thr Lys Arg

325 330 335

Ser Val Ile Cys Asn Gln Asp Tyr Ala Thr Pro Met Thr Asn Asn Met

340 345 350

Arg Glu Cys Leu Thr Gly Ser Thr Glu Lys Cys Pro Arg Glu Leu Val

355 360 365

Val Ser Ser His Val Pro Arg Phe Ala Leu Ser Asn Gly Val Leu Phe

370 375 380

Ala Asn Cys Ile Ser Val Thr Cys Gln Cys Gln Thr Thr Gly Arg Ala

385 390 395 400

Ile Ser Gln Ser Gly Glu Gln Thr Leu Leu Met Ile Asp Asn Thr Thr

405 410 415

Cys Pro Thr Ala Val Leu Gly Asn Val Ile Ile Ser Leu Gly Lys Tyr

420 425 430

Leu Gly Ser Val Asn Tyr Asn Ser Glu Gly Ile Ala Ile Gly Pro Pro

435 440 445

Val Phe Thr Asp Lys Val Asp Ile Ser Ser Gln Ile Ser Ser Met Asn

450 455 460

Gln Ser Leu Gln Gln Ser Lys Asp Tyr Ile Lys Glu Ala Gln Arg Leu

465 470 475 480

Leu Asp Thr Val Asn Pro Ser Leu Ile Ser Met Leu Ser Met Ile Ile

485 490 495

Leu Tyr Val Leu Ser Ile Ala Ser Leu Cys Ile Gly Leu Ile Thr Phe

500 505 510

Ile Ser Phe Ile Ile Val Glu Lys Lys Arg Asn Thr Tyr Ser Arg Leu

515 520 525

Glu Asp Arg Arg Val Arg Pro Thr Ser Ser Gly Asp Leu Tyr Tyr Ile

530 535 540

Gly Thr

545

<210> 53

<211> 602

<212> PRT

<213> 尼帕病毒

<400> 53

Met Pro Ala Glu Asn Lys Lys Val Arg Phe Glu Asn Thr Thr Ser Asp

1 5 10 15

Lys Gly Lys Ile Pro Ser Lys Val Ile Lys Ser Tyr Tyr Gly Thr Met

20 25 30

Asp Ile Lys Lys Ile Asn Glu Gly Leu Leu Asp Ser Lys Ile Leu Ser

35 40 45

Ala Phe Asn Thr Val Ile Ala Leu Leu Gly Ser Ile Val Ile Ile Val

50 55 60

Met Asn Ile Met Ile Ile Gln Asn Tyr Thr Arg Ser Thr Asp Asn Gln

65 70 75 80

Ala Val Ile Lys Asp Ala Leu Gln Gly Ile Gln Gln Gln Ile Lys Gly

85 90 95

Leu Ala Asp Lys Ile Gly Thr Glu Ile Gly Pro Lys Val Ser Leu Ile

100 105 110

Asp Thr Ser Ser Thr Ile Thr Ile Pro Ala Asn Ile Gly Leu Leu Gly

115 120 125

Ser Lys Ile Ser Gln Ser Thr Ala Ser Ile Asn Glu Asn Val Asn Glu

130 135 140

Lys Cys Lys Phe Thr Leu Pro Pro Leu Lys Ile His Glu Cys Asn Ile

145 150 155 160

Ser Cys Pro Asn Pro Leu Pro Phe Arg Glu Tyr Arg Pro Gln Thr Glu

165 170 175

Gly Val Ser Asn Leu Val Gly Leu Pro Asn Asn Ile Cys Leu Gln Lys

180 185 190

Thr Ser Asn Gln Ile Leu Lys Pro Lys Leu Ile Ser Tyr Thr Leu Pro

195 200 205

Val Val Gly Gln Ser Gly Thr Cys Ile Thr Asp Pro Leu Leu Ala Met

210 215 220

Asp Glu Gly Tyr Phe Ala Tyr Ser His Leu Glu Arg Ile Gly Ser Cys

225 230 235 240

Ser Arg Gly Val Ser Lys Gln Arg Ile Ile Gly Val Gly Glu Val Leu

245 250 255

Asp Arg Gly Asp Glu Val Pro Ser Leu Phe Met Thr Asn Val Trp Thr

260 265 270

Pro Pro Asn Pro Asn Thr Val Tyr His Cys Ser Ala Val Tyr Asn Asn

275 280 285

Glu Phe Tyr Tyr Val Leu Cys Ala Val Ser Thr Val Gly Asp Pro Ile

290 295 300

Leu Asn Ser Thr Tyr Trp Ser Gly Ser Leu Met Met Thr Arg Leu Ala

305 310 315 320

Val Lys Pro Lys Ser Asn Gly Gly Gly Tyr Asn Gln His Gln Leu Ala

325 330 335

Leu Arg Ser Ile Glu Lys Gly Arg Tyr Asp Lys Val Met Pro Tyr Gly

340 345 350

Pro Ser Gly Ile Lys Gln Gly Asp Thr Leu Tyr Phe Pro Ala Val Gly

355 360 365

Phe Leu Val Arg Thr Glu Phe Lys Tyr Asn Asp Ser Asn Cys Pro Ile

370 375 380

Thr Lys Cys Gln Tyr Ser Lys Pro Glu Asn Cys Arg Leu Ser Met Gly

385 390 395 400

Ile Arg Pro Asn Ser His Tyr Ile Leu Arg Ser Gly Leu Leu Lys Tyr

405 410 415

Asn Leu Ser Asp Gly Glu Asn Pro Lys Val Val Phe Ile Glu Ile Ser

420 425 430

Asp Gln Arg Leu Ser Ile Gly Ser Pro Ser Lys Ile Tyr Asp Ser Leu

435 440 445

Gly Gln Pro Val Phe Tyr Gln Ala Ser Phe Ser Trp Asp Thr Met Ile

450 455 460

Lys Phe Gly Asp Val Leu Thr Val Asn Pro Leu Val Val Asn Trp Arg

465 470 475 480

Asn Asn Thr Val Ile Ser Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe

485 490 495

Asn Thr Cys Pro Glu Ile Cys Trp Glu Gly Val Tyr Asn Asp Ala Phe

500 505 510

Leu Ile Asp Arg Ile Asn Trp Ile Ser Ala Gly Val Phe Leu Asp Ser

515 520 525

Asn Gln Thr Ala Glu Asn Pro Val Phe Thr Val Phe Lys Asp Asn Glu

530 535 540

Ile Leu Tyr Arg Ala Gln Leu Ala Ser Glu Asp Thr Asn Ala Gln Lys

545 550 555 560

Thr Ile Thr Asn Cys Phe Leu Leu Lys Asn Lys Ile Trp Cys Ile Ser

565 570 575

Leu Val Glu Ile Tyr Asp Thr Gly Asp Asn Val Ile Arg Pro Lys Leu

580 585 590

Phe Ala Val Lys Ile Pro Glu Gln Cys Thr

595 600

<210> 54

<211> 602

<212> PRT

<213> 尼帕病毒

<400> 54

Met Pro Thr Glu Ser Lys Lys Val Arg Phe Glu Asn Thr Ala Ser Asp

1 5 10 15

Lys Gly Lys Asn Pro Ser Lys Val Ile Lys Ser Tyr Tyr Gly Thr Met

20 25 30

Asp Ile Lys Lys Ile Asn Glu Gly Leu Leu Asp Ser Lys Ile Leu Ser

35 40 45

Ala Phe Asn Thr Val Ile Ala Leu Leu Gly Ser Ile Val Ile Ile Val

50 55 60

Met Asn Ile Met Ile Ile Gln Asn Tyr Thr Arg Ser Thr Asp Asn Gln

65 70 75 80

Ala Met Ile Lys Asp Ala Leu Gln Ser Ile Gln Gln Gln Ile Lys Gly

85 90 95

Leu Ala Asp Lys Ile Gly Thr Glu Ile Gly Pro Lys Val Ser Leu Ile

100 105 110

Asp Thr Ser Ser Thr Ile Thr Ile Pro Ala Asn Ile Gly Leu Leu Gly

115 120 125

Ser Lys Ile Ser Gln Ser Thr Ala Ser Ile Asn Glu Asn Val Asn Glu

130 135 140

Lys Cys Lys Phe Thr Leu Pro Pro Leu Lys Ile His Glu Cys Asn Ile

145 150 155 160

Ser Cys Pro Asn Pro Leu Pro Phe Arg Glu Tyr Lys Pro Gln Thr Glu

165 170 175

Gly Val Ser Asn Leu Val Gly Leu Pro Asn Asn Ile Cys Leu Gln Lys

180 185 190

Thr Ser Asn Gln Ile Leu Lys Pro Lys Leu Ile Ser Tyr Thr Leu Pro

195 200 205

Val Val Gly Gln Ser Gly Thr Cys Ile Thr Asp Pro Leu Leu Ala Met

210 215 220

Asp Glu Gly Tyr Phe Ala Tyr Ser His Leu Glu Lys Ile Gly Ser Cys

225 230 235 240

Ser Arg Gly Val Ser Lys Gln Arg Ile Ile Gly Val Gly Glu Val Leu

245 250 255

Asp Arg Gly Asp Glu Val Pro Ser Leu Phe Met Thr Asn Val Trp Thr

260 265 270

Pro Ser Asn Pro Asn Thr Val Tyr His Cys Ser Ala Val Tyr Asn Asn

275 280 285

Glu Phe Tyr Tyr Val Leu Cys Ala Val Ser Val Val Gly Asp Pro Ile

290 295 300

Leu Asn Ser Thr Tyr Trp Ser Gly Ser Leu Met Met Thr Arg Leu Ala

305 310 315 320

Val Lys Pro Lys Asn Asn Gly Glu Ser Tyr Asn Gln His Gln Phe Ala

325 330 335

Leu Arg Asn Ile Glu Lys Gly Lys Tyr Asp Lys Val Met Pro Tyr Gly

340 345 350

Pro Ser Gly Ile Lys Gln Gly Asp Thr Leu Tyr Phe Pro Ala Val Gly

355 360 365

Phe Leu Val Arg Thr Glu Phe Lys Tyr Asn Asp Ser Asn Cys Pro Ile

370 375 380

Ala Glu Cys Gln Tyr Ser Lys Pro Glu Asn Cys Arg Leu Ser Met Gly

385 390 395 400

Ile Arg Pro Asn Ser His Tyr Ile Leu Arg Ser Gly Leu Leu Lys Tyr

405 410 415

Asn Leu Ser Asp Glu Glu Asn Ser Lys Ile Val Phe Ile Glu Ile Ser

420 425 430

Asp Gln Arg Leu Ser Ile Gly Ser Pro Ser Lys Ile Tyr Asp Ser Leu

435 440 445

Gly Gln Pro Val Phe Tyr Gln Ala Ser Phe Ser Trp Asp Thr Met Ile

450 455 460

Lys Phe Gly Asp Val Gln Thr Val Asn Pro Leu Val Val Asn Trp Arg

465 470 475 480

Asp Asn Thr Val Ile Ser Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe

485 490 495

Asn Lys Cys Pro Glu Val Cys Trp Glu Gly Val Tyr Asn Asp Ala Phe

500 505 510

Leu Ile Asp Arg Ile Asn Trp Ile Ser Ala Gly Val Phe Leu Asp Ser

515 520 525

Asn Gln Thr Ala Glu Asn Pro Val Phe Thr Val Phe Lys Asp Asn Glu

530 535 540

Val Leu Tyr Arg Ala Gln Leu Ala Ser Glu Asp Thr Asn Ala Gln Lys

545 550 555 560

Thr Ile Thr Asn Cys Phe Leu Leu Lys Asn Lys Ile Trp Cys Ile Ser

565 570 575

Leu Val Glu Ile Tyr Asp Thr Gly Asp Asn Val Ile Arg Pro Lys Leu

580 585 590

Phe Ala Val Lys Ile Pro Glu Gln Cys Thr

595 600

<210> 55

<211> 163

<212> PRT

<213> 人工序列

<220>

<223> 重组铁蛋白序列

<400> 55

Asp Ile Ile Lys Leu Leu Asn Glu Gln Val Asn Lys Glu Met Gln Ser

1 5 10 15

Ser Asn Leu Tyr Met Ser Met Ser Ser Trp Cys Tyr Thr His Ser Leu

20 25 30

Asp Gly Ala Gly Leu Phe Leu Phe Asp His Ala Ala Glu Glu Tyr Glu

35 40 45

His Ala Lys Lys Leu Ile Ile Phe Leu Asn Glu Asn Asn Val Pro Val

50 55 60

Gln Leu Thr Ser Ile Ser Ala Pro Glu His Lys Phe Glu Gly Leu Thr

65 70 75 80

Gln Ile Phe Gln Lys Ala Tyr Glu His Glu Gln His Ile Ser Glu Ser

85 90 95

Ile Asn Asn Ile Val Asp His Ala Ile Lys Ser Lys Asp His Ala Thr

100 105 110

Phe Asn Phe Leu Gln Trp Tyr Val Ala Glu Gln His Glu Glu Glu Val

115 120 125

Leu Phe Lys Asp Ile Leu Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn

130 135 140

His Gly Leu Tyr Leu Ala Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser

145 150 155 160

Arg Lys Ser

<210> 56

<211> 154

<212> PRT

<213> 人工序列

<220>

<223> 重组二氧四氢蝶啶合酶序列

<400> 56

Met Gln Ile Tyr Glu Gly Lys Leu Thr Ala Glu Gly Leu Arg Phe Gly

1 5 10 15

Ile Val Ala Ser Arg Phe Asn His Ala Leu Val Asp Arg Leu Val Glu

20 25 30

Gly Ala Ile Asp Cys Ile Val Arg His Gly Gly Arg Glu Glu Asp Ile

35 40 45

Thr Leu Val Arg Val Pro Gly Ser Trp Glu Ile Pro Val Ala Ala Gly

50 55 60

Glu Leu Ala Arg Lys Glu Asp Ile Asp Ala Val Ile Ala Ile Gly Val

65 70 75 80

Leu Ile Arg Gly Ala Thr Pro His Phe Asp Tyr Ile Ala Ser Glu Val

85 90 95

Ser Lys Gly Leu Ala Asp Leu Ser Leu Glu Leu Arg Lys Pro Ile Thr

100 105 110

Phe Gly Val Ile Thr Ala Asp Thr Leu Glu Gln Ala Ile Glu Arg Ala

115 120 125

Gly Thr Lys His Gly Asn Lys Gly Trp Glu Ala Ala Leu Ser Ala Ile

130 135 140

Glu Met Ala Asn Leu Phe Lys Ser Leu Arg

145 150

<210> 57

<211> 265

<212> PRT

<213> 人工序列

<220>

<223> 重组囊包蛋白序列

<400> 57

Met Glu Phe Leu Lys Arg Ser Phe Ala Pro Leu Thr Glu Lys Gln Trp

1 5 10 15

Gln Glu Ile Asp Asn Arg Ala Arg Glu Ile Phe Lys Thr Gln Leu Tyr

20 25 30

Gly Arg Lys Phe Val Asp Val Glu Gly Pro Tyr Gly Trp Glu Tyr Ala

35 40 45

Ala His Pro Leu Gly Glu Val Glu Val Leu Ser Asp Glu Asn Glu Val

50 55 60

Val Lys Trp Gly Leu Arg Lys Ser Leu Pro Leu Ile Glu Leu Arg Ala

65 70 75 80

Thr Phe Thr Leu Asp Leu Trp Glu Leu Asp Asn Leu Glu Arg Gly Lys

85 90 95

Pro Asn Val Asp Leu Ser Ser Leu Glu Glu Thr Val Arg Lys Val Ala

100 105 110

Glu Phe Glu Asp Glu Val Ile Phe Arg Gly Cys Glu Lys Ser Gly Val

115 120 125

Lys Gly Leu Leu Ser Phe Glu Glu Arg Lys Ile Glu Cys Gly Ser Thr

130 135 140

Pro Lys Asp Leu Leu Glu Ala Ile Val Arg Ala Leu Ser Ile Phe Ser

145 150 155 160

Lys Asp Gly Ile Glu Gly Pro Tyr Thr Leu Val Ile Asn Thr Asp Arg

165 170 175

Trp Ile Asn Phe Leu Lys Glu Glu Ala Gly His Tyr Pro Leu Glu Lys

180 185 190

Arg Val Glu Glu Cys Leu Arg Gly Gly Lys Ile Ile Thr Thr Pro Arg

195 200 205

Ile Glu Asp Ala Leu Val Val Ser Glu Arg Gly Gly Asp Phe Lys Leu

210 215 220

Ile Leu Gly Gln Asp Leu Ser Ile Gly Tyr Glu Asp Arg Glu Lys Asp

225 230 235 240

Ala Val Arg Leu Phe Ile Thr Glu Thr Phe Thr Phe Gln Val Val Asn

245 250 255

Pro Glu Ala Leu Ile Leu Leu Lys Phe

260 265

<210> 58

<211> 265

<212> PRT

<213> 人工序列

<220>

<223> 重组硫氧化酶还原酶序列

<400> 58

Met Glu Phe Leu Lys Arg Ser Phe Ala Pro Leu Thr Glu Lys Gln Trp

1 5 10 15

Gln Glu Ile Asp Asn Arg Ala Arg Glu Ile Phe Lys Thr Gln Leu Tyr

20 25 30

Gly Arg Lys Phe Val Asp Val Glu Gly Pro Tyr Gly Trp Glu Tyr Ala

35 40 45

Ala His Pro Leu Gly Glu Val Glu Val Leu Ser Asp Glu Asn Glu Val

50 55 60

Val Lys Trp Gly Leu Arg Lys Ser Leu Pro Leu Ile Glu Leu Arg Ala

65 70 75 80

Thr Phe Thr Leu Asp Leu Trp Glu Leu Asp Asn Leu Glu Arg Gly Lys

85 90 95

Pro Asn Val Asp Leu Ser Ser Leu Glu Glu Thr Val Arg Lys Val Ala

100 105 110

Glu Phe Glu Asp Glu Val Ile Phe Arg Gly Cys Glu Lys Ser Gly Val

115 120 125

Lys Gly Leu Leu Ser Phe Glu Glu Arg Lys Ile Glu Cys Gly Ser Thr

130 135 140

Pro Lys Asp Leu Leu Glu Ala Ile Val Arg Ala Leu Ser Ile Phe Ser

145 150 155 160

Lys Asp Gly Ile Glu Gly Pro Tyr Thr Leu Val Ile Asn Thr Asp Arg

165 170 175

Trp Ile Asn Phe Leu Lys Glu Glu Ala Gly His Tyr Pro Leu Glu Lys

180 185 190

Arg Val Glu Glu Cys Leu Arg Gly Gly Lys Ile Ile Thr Thr Pro Arg

195 200 205

Ile Glu Asp Ala Leu Val Val Ser Glu Arg Gly Gly Asp Phe Lys Leu

210 215 220

Ile Leu Gly Gln Asp Leu Ser Ile Gly Tyr Glu Asp Arg Glu Lys Asp

225 230 235 240

Ala Val Arg Leu Phe Ile Thr Glu Thr Phe Thr Phe Gln Val Val Asn

245 250 255

Pro Glu Ala Leu Ile Leu Leu Lys Phe

260 265

<210> 59

<211> 976

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 59

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Gly Ile Leu His Tyr Glu Lys Leu Ser Lys Ile

20 25 30

Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro

35 40 45

Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn Val Ser Asn Met

50 55 60

Ser Gln Cys Thr Gly Ser Val Met Glu Asn Tyr Lys Thr Arg Leu Asn

65 70 75 80

Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile Tyr Lys Asn Asn

85 90 95

Thr His Asp Cys Val Gly Asp Val Arg Leu Ala Gly Val Cys Met Ala

100 105 110

Gly Val Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile Thr Ala Gly Val

115 120 125

Ala Leu Tyr Glu Ala Met Lys Asn Ala Asp Asn Ile Asn Lys Leu Lys

130 135 140

Ser Ser Ile Glu Ser Thr Asn Glu Ala Val Val Lys Leu Gln Glu Thr

145 150 155 160

Ala Glu Lys Thr Val Tyr Val Phe Thr Ala Leu Gln Asp Tyr Ile Asn

165 170 175

Thr Asn Leu Val Pro Thr Ile Asp Lys Ile Pro Cys Lys Gln Thr Glu

180 185 190

Leu Ser Leu Asp Leu Ala Leu Ser Lys Tyr Leu Ser Asp Leu Leu Phe

195 200 205

Val Phe Gly Pro Asn Leu Gln Asp Pro Val Ser Asn Ser Met Thr Ile

210 215 220

Gln Ala Ile Ser Gln Ala Phe Gly Gly Asn Tyr Glu Thr Leu Leu Arg

225 230 235 240

Thr Leu Gly Tyr Ala Thr Glu Asp Phe Asp Asp Leu Leu Glu Ser Asp

245 250 255

Ser Ile Thr Gly Gln Ile Ile Tyr Val Asp Leu Ser Ser Tyr Tyr Ile

260 265 270

Ile Val Arg Val Tyr Phe Pro Ile Leu Thr Glu Ile Gln Gln Ala Tyr

275 280 285

Ile Gln Glu Leu Leu Pro Val Ser Phe Asn Asn Asp Asn Ser Glu Trp

290 295 300

Ile Ser Ile Val Pro Asn Phe Ile Leu Val Arg Asn Thr Leu Ile Ser

305 310 315 320

Asn Ile Glu Ile Gly Phe Cys Leu Ile Thr Lys Arg Ser Val Ile Cys

325 330 335

Asn Gln Asp Tyr Ala Thr Pro Met Thr Asn Asn Met Arg Glu Cys Leu

340 345 350

Thr Gly Ser Thr Glu Lys Cys Pro Arg Glu Leu Val Val Ser Ser His

355 360 365

Val Pro Arg Phe Ala Leu Ser Asn Gly Val Leu Phe Ala Asn Cys Ile

370 375 380

Ser Val Thr Cys Gln Cys Gln Thr Thr Gly Arg Ala Ile Ser Gln Ser

385 390 395 400

Gly Glu Gln Thr Leu Leu Met Ile Asp Asn Thr Thr Cys Pro Thr Ala

405 410 415

Val Leu Gly Asn Val Ile Ile Ser Leu Gly Lys Tyr Leu Gly Ser Val

420 425 430

Asn Tyr Asn Ser Glu Gly Ile Ala Ile Gly Pro Pro Val Phe Thr Asp

435 440 445

Lys Val Asp Ile Ser Ser Gln Ile Ser Ser Met Asn Gln Ser Leu Gln

450 455 460

Gln Ser Lys Asp Tyr Ile Lys Glu Ala Gln Arg Leu Leu Asp Thr Val

465 470 475 480

Asn Pro Ser Leu Lys Leu Met Lys Gln Ile Glu Asp Lys Ile Glu Glu

485 490 495

Ile Leu Ser Lys Ile Tyr His Ile Glu Asn Glu Ile Ala Arg Ile Lys

500 505 510

Lys Leu Ile Gly Glu Ala Pro Gly Ser Gly Gly Gly Gly Gly Gly Val

515 520 525

Ser Asn Leu Val Gly Leu Pro Asn Asn Ile Cys Leu Gln Lys Thr Ser

530 535 540

Asn Gln Ile Leu Lys Pro Lys Leu Ile Ser Tyr Thr Leu Pro Val Val

545 550 555 560

Gly Gln Ser Gly Thr Cys Ile Thr Asp Pro Leu Leu Ala Met Asp Glu

565 570 575

Gly Tyr Phe Ala Tyr Ser His Leu Glu Arg Ile Gly Ser Cys Ser Arg

580 585 590

Gly Val Ser Lys Gln Arg Ile Ile Gly Val Gly Glu Val Leu Asp Arg

595 600 605

Gly Asp Glu Val Pro Ser Leu Phe Met Thr Asn Val Trp Thr Pro Pro

610 615 620

Asn Pro Asn Thr Val Tyr His Cys Ser Ala Val Tyr Asn Asn Glu Phe

625 630 635 640

Tyr Tyr Val Leu Cys Ala Val Ser Thr Val Gly Asp Pro Ile Leu Asn

645 650 655

Ser Thr Tyr Trp Ser Gly Ser Leu Met Met Thr Arg Leu Ala Val Lys

660 665 670

Pro Lys Ser Asn Gly Gly Gly Tyr Asn Gln His Gln Leu Ala Leu Arg

675 680 685

Ser Ile Glu Lys Gly Arg Tyr Asp Lys Val Met Pro Tyr Gly Pro Ser

690 695 700

Gly Ile Lys Gln Gly Asp Thr Leu Tyr Phe Pro Ala Val Gly Phe Leu

705 710 715 720

Val Arg Thr Glu Phe Lys Tyr Asn Asp Ser Asn Cys Pro Ile Thr Lys

725 730 735

Cys Gln Tyr Ser Lys Pro Glu Asn Cys Arg Leu Ser Met Gly Ile Arg

740 745 750

Pro Asn Ser His Tyr Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn Leu

755 760 765

Ser Asp Gly Glu Asn Pro Lys Val Val Phe Ile Glu Ile Ser Asp Gln

770 775 780

Arg Leu Ser Ile Gly Ser Pro Ser Lys Ile Tyr Asp Ser Leu Gly Gln

785 790 795 800

Pro Val Phe Tyr Gln Ala Ser Phe Ser Trp Asp Thr Met Ile Lys Phe

805 810 815

Gly Asp Val Leu Thr Val Asn Pro Leu Val Val Asn Trp Arg Asn Asn

820 825 830

Thr Val Ile Ser Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn Thr

835 840 845

Cys Pro Glu Ile Cys Trp Glu Gly Val Tyr Asn Asp Ala Phe Leu Ile

850 855 860

Asp Arg Ile Asn Trp Ile Ser Ala Gly Val Phe Leu Asp Ser Asn Gln

865 870 875 880

Thr Ala Glu Asn Pro Val Phe Thr Val Phe Lys Asp Asn Glu Ile Leu

885 890 895

Tyr Arg Ala Gln Leu Ala Ser Glu Asp Thr Asn Ala Gln Lys Thr Ile

900 905 910

Thr Asn Cys Phe Leu Leu Lys Asn Lys Ile Trp Cys Ile Ser Leu Val

915 920 925

Glu Ile Tyr Asp Thr Gly Asp Asn Val Ile Arg Pro Lys Leu Phe Ala

930 935 940

Val Lys Ile Pro Glu Gln Cys Thr Gly Gly Leu Val Pro Arg Gly Ser

945 950 955 960

His His His His His His Ser Ala Trp Ser His Pro Gln Phe Glu Lys

965 970 975

<210> 60

<211> 970

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 60

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Gly Ile Leu His Tyr Glu Lys Leu Ser Lys Ile

20 25 30

Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro

35 40 45

Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn Val Ser Asn Met

50 55 60

Ser Gln Cys Thr Gly Ser Val Met Glu Asn Tyr Lys Thr Arg Leu Asn

65 70 75 80

Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile Tyr Lys Asn Asn

85 90 95

Thr His Asp Cys Val Gly Asp Val Arg Leu Ala Gly Val Cys Met Ala

100 105 110

Gly Val Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile Thr Ala Gly Val

115 120 125

Ala Leu Tyr Glu Ala Met Lys Asn Ala Asp Asn Ile Asn Lys Leu Lys

130 135 140

Ser Ser Ile Glu Ser Thr Asn Glu Ala Val Val Lys Leu Gln Glu Thr

145 150 155 160

Ala Glu Lys Thr Val Tyr Val Phe Thr Ala Leu Gln Asp Tyr Ile Asn

165 170 175

Thr Asn Leu Val Pro Thr Ile Asp Lys Ile Pro Cys Lys Gln Thr Glu

180 185 190

Leu Ser Leu Asp Leu Ala Leu Ser Lys Tyr Leu Ser Asp Leu Leu Phe

195 200 205

Val Phe Gly Pro Asn Leu Gln Asp Pro Val Ser Asn Ser Met Thr Ile

210 215 220

Gln Ala Ile Ser Gln Ala Phe Gly Gly Asn Tyr Glu Thr Leu Leu Arg

225 230 235 240

Thr Leu Gly Tyr Ala Thr Glu Asp Phe Asp Asp Leu Leu Glu Ser Asp

245 250 255

Ser Ile Thr Gly Gln Ile Ile Tyr Val Asp Leu Ser Ser Tyr Tyr Ile

260 265 270

Ile Val Arg Val Tyr Phe Pro Ile Leu Thr Glu Ile Gln Gln Ala Tyr

275 280 285

Ile Gln Glu Leu Leu Pro Val Ser Phe Asn Asn Asp Asn Ser Glu Trp

290 295 300

Ile Ser Ile Val Pro Asn Phe Ile Leu Val Arg Asn Thr Leu Ile Ser

305 310 315 320

Asn Ile Glu Ile Gly Phe Cys Leu Ile Thr Lys Arg Ser Val Ile Cys

325 330 335

Asn Gln Asp Tyr Ala Thr Pro Met Thr Asn Asn Met Arg Glu Cys Leu

340 345 350

Thr Gly Ser Thr Glu Lys Cys Pro Arg Glu Leu Val Val Ser Ser His

355 360 365

Val Pro Arg Phe Ala Leu Ser Asn Gly Val Leu Phe Ala Asn Cys Ile

370 375 380

Ser Val Thr Cys Gln Cys Gln Thr Thr Gly Arg Ala Ile Ser Gln Ser

385 390 395 400

Gly Glu Gln Thr Leu Leu Met Ile Asp Asn Thr Thr Cys Pro Thr Ala

405 410 415

Val Leu Gly Asn Val Ile Ile Ser Leu Gly Lys Tyr Leu Gly Ser Val

420 425 430

Asn Tyr Asn Ser Glu Gly Ile Ala Ile Gly Pro Pro Val Phe Thr Asp

435 440 445

Lys Val Asp Ile Ser Ser Gln Ile Ser Ser Met Asn Gln Ser Leu Gln

450 455 460

Gln Ser Lys Asp Tyr Ile Lys Glu Ala Gln Arg Leu Leu Asp Thr Val

465 470 475 480

Asn Pro Ser Leu Gly Ser Gly Tyr Ile Pro Glu Ala Pro Arg Asp Gly

485 490 495

Gln Ala Tyr Val Arg Lys Asp Gly Glu Trp Val Leu Leu Ser Thr Phe

500 505 510

Leu Gly Ser Gly Gly Gly Gly Gly Gly Val Ser Asn Leu Val Gly Leu

515 520 525

Pro Asn Asn Ile Cys Leu Gln Lys Thr Ser Asn Gln Ile Leu Lys Pro

530 535 540

Lys Leu Ile Ser Tyr Thr Leu Pro Val Val Gly Gln Ser Gly Thr Cys

545 550 555 560

Ile Thr Asp Pro Leu Leu Ala Met Asp Glu Gly Tyr Phe Ala Tyr Ser

565 570 575

His Leu Glu Arg Ile Gly Ser Cys Ser Arg Gly Val Ser Lys Gln Arg

580 585 590

Ile Ile Gly Val Gly Glu Val Leu Asp Arg Gly Asp Glu Val Pro Ser

595 600 605

Leu Phe Met Thr Asn Val Trp Thr Pro Pro Asn Pro Asn Thr Val Tyr

610 615 620

His Cys Ser Ala Val Tyr Asn Asn Glu Phe Tyr Tyr Val Leu Cys Ala

625 630 635 640

Val Ser Thr Val Gly Asp Pro Ile Leu Asn Ser Thr Tyr Trp Ser Gly

645 650 655

Ser Leu Met Met Thr Arg Leu Ala Val Lys Pro Lys Ser Asn Gly Gly

660 665 670

Gly Tyr Asn Gln His Gln Leu Ala Leu Arg Ser Ile Glu Lys Gly Arg

675 680 685

Tyr Asp Lys Val Met Pro Tyr Gly Pro Ser Gly Ile Lys Gln Gly Asp

690 695 700

Thr Leu Tyr Phe Pro Ala Val Gly Phe Leu Val Arg Thr Glu Phe Lys

705 710 715 720

Tyr Asn Asp Ser Asn Cys Pro Ile Thr Lys Cys Gln Tyr Ser Lys Pro

725 730 735

Glu Asn Cys Arg Leu Ser Met Gly Ile Arg Pro Asn Ser His Tyr Ile

740 745 750

Leu Arg Ser Gly Leu Leu Lys Tyr Asn Leu Ser Asp Gly Glu Asn Pro

755 760 765

Lys Val Val Phe Ile Glu Ile Ser Asp Gln Arg Leu Ser Ile Gly Ser

770 775 780

Pro Ser Lys Ile Tyr Asp Ser Leu Gly Gln Pro Val Phe Tyr Gln Ala

785 790 795 800

Ser Phe Ser Trp Asp Thr Met Ile Lys Phe Gly Asp Val Leu Thr Val

805 810 815

Asn Pro Leu Val Val Asn Trp Arg Asn Asn Thr Val Ile Ser Arg Pro

820 825 830

Gly Gln Ser Gln Cys Pro Arg Phe Asn Thr Cys Pro Glu Ile Cys Trp

835 840 845

Glu Gly Val Tyr Asn Asp Ala Phe Leu Ile Asp Arg Ile Asn Trp Ile

850 855 860

Ser Ala Gly Val Phe Leu Asp Ser Asn Gln Thr Ala Glu Asn Pro Val

865 870 875 880

Phe Thr Val Phe Lys Asp Asn Glu Ile Leu Tyr Arg Ala Gln Leu Ala

885 890 895

Ser Glu Asp Thr Asn Ala Gln Lys Thr Ile Thr Asn Cys Phe Leu Leu

900 905 910

Lys Asn Lys Ile Trp Cys Ile Ser Leu Val Glu Ile Tyr Asp Thr Gly

915 920 925

Asp Asn Val Ile Arg Pro Lys Leu Phe Ala Val Lys Ile Pro Glu Gln

930 935 940

Cys Thr Gly Gly Leu Val Pro Arg Gly Ser His His His His His His

945 950 955 960

Ser Ala Trp Ser His Pro Gln Phe Glu Lys

965 970

<210> 61

<211> 3038

<212> DNA

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 61

tctagagcca ccatgtactc tatgcagctg gccagctgcg tgaccctgac actggtgctg 60

ctggtgaact ctcagggcat cctgcactac gagaagctga gcaagatcgg cctggtgaag 120

ggcgtgacca gaaagtataa gatcaagtcc aacccactga caaaggacat cgtgatcaag 180

atgatcccca acgtgagcaa tatgtctcag tgtaccggct ctgtgatgga gaactacaag 240

acccgcctga atggcatcct gacaccaatc aagggcgccc tggagatcta taagaacaat 300

acacacgact gcgtgggcga tgtgcggctg gcaggcgtgt gcatggcagg agtggcaatc 360

ggaatcgcaa ccgcagcaca gatcacagca ggagtggccc tgtatgaggc catgaagaac 420

gccgacaaca tcaataagct gaagagctcc atcgagagca ccaatgaggc cgtggtgaag 480

ctgcaggaga cagccgagaa gacagtgtac gtgttcacag ccctgcagga ctatatcaac 540

accaatctgg tgcccacaat cgataagatc ccctgcaagc agaccgagct gtccctggac 600

ctggccctgt ctaagtacct gagcgatctg ctgttcgtgt ttggcccaaa cctgcaggac 660

cccgtgtcca attctatgac aatccaggcc atctcccagg ccttcggcgg caattacgag 720

acactgctga gaacactggg ctatgccacc gaggactttg acgatctgct ggagagcgat 780

tccatcacag gccagatcat ctatgtggat ctgtctagct actatatcat cgtgagggtg 840

tacttcccta tcctgaccga gatccagcag gcctatatcc aggagctgct gccagtgagc 900

ttcaacaatg acaattccga gtggatctct atcgtgccca actttatcct ggtgcggaac 960

accctgatca gcaatatcga gatcggcttt tgcctgatca caaagagatc cgtgatctgt 1020

aatcaggact acgccacccc catgacaaac aatatgaggg agtgcctgac cggctccaca 1080

gagaagtgtc cccgggagct ggtggtgtcc tctcacgtgc ctagattcgc cctgtccaac 1140

ggcgtgctgt ttgccaattg catctctgtg acctgccagt gtcagaccac aggaagggca 1200

atctctcaga gcggagagca gaccctgctg atgatcgata acaccacatg tcctacagcc 1260

gtgctgggca atgtgatcat cagcctgggc aagtacctgg gctccgtgaa ctataattct 1320

gagggaatcg caatcggacc acccgtgttc accgacaagg tggatatcag ctcccagatc 1380

tctagcatga accagagcct gcagcagtcc aaggactaca tcaaggaggc ccagcggctg 1440

ctggataccg tgaatccttc tctgaagctg atgaagcaga tcgaggataa gatcgaggag 1500

atcctgagca agatctatca catcgagaac gagatcgcca ggatcaagaa gctgatcgga 1560

gaggcacctg gatctggtta catcccagag gctccgcggg atggacaggc ctacgtgaga 1620

aaggacggcg agtgggtgct gctgagcacc ttcctgggaa gcggtggagg aggcggaggc 1680

gtgagcaatc tggtgggcct gcccaacaat atctgtctgc agaagacctc caaccagatc 1740

ctgaagccca agctgatctc ctatacactg cctgtggtgg gccagtctgg cacctgcatc 1800

acagaccctc tgctggccat ggatgagggc tacttcgcct attctcacct ggagaggatc 1860

ggctcctgtt ctcgcggcgt gagcaagcag cggatcatcg gagtgggaga ggtgctggac 1920

aggggcgatg aggtgccttc cctgttcatg accaacgtgt ggacaccacc caatccaaac 1980

accgtgtacc actgctctgc cgtgtataac aatgagtttt actacgtgct gtgcgccgtg 2040

agcaccgtgg gcgatcctat cctgaactcc acatactgga gcggctccct gatgatgacc 2100

agactggccg tgaagccaaa gtccaatggc ggcggctata accagcacca gctggccctg 2160

agatctatcg agaagggcag gtacgataaa gtgatgcctt atggcccatc tggcatcaag 2220

cagggcgaca cactgtactt ccccgccgtg ggctttctgg tgaggaccga gttcaagtac 2280

aatgactcca actgccctat cacaaagtgt cagtattcta agccagagaa ttgccgcctg 2340

agcatgggca tccggcccaa ctctcactac atcctgagaa gcggcctgct gaagtataat 2400

ctgagcgacg gcgagaaccc taaggtggtg tttatcgaga tctccgatca gaggctgtct 2460

atcggctctc ccagcaagat ctacgactcc ctgggccagc ccgtgttcta ccaggcctcc 2520

ttttcttggg acacaatgat caagttcggc gatgtgctga ccgtgaatcc actggtggtg 2580

aactggagaa acaataccgt gatcagcagg ccaggacagt cccagtgtcc tcgctttaac 2640

acatgcccag agatctgttg ggagggcgtg tacaatgacg ccttcctgat cgatcggatc 2700

aactggatct ccgccggcgt gtttctggac tctaatcaga ccgccgagaa ccccgtgttc 2760

acagtgttta aggataatga gatcctgtac agggcacagc tggcaagcga ggacaccaac 2820

gcccagaaga ccatcacaaa ttgcttcctg ctgaagaaca agatctggtg tatctccctg 2880

gtggagatct atgacaccgg cgataacgtg atccggccaa agctgtttgc cgtgaagatc 2940

cccgagcagt gcacaggcgg cctggtgcct agaggctctc accaccacca tcaccacagc 3000

gcctggtccc acccccagtt cgagaagtga taggatcc 3038

<210> 62

<211> 3044

<212> DNA

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 62

tctagaccac catgtactca atgcagctgg cctcttgcgt cacactgaca ctggtcctgc 60

tggtcaactc acagagacca cagaccgagg gcgtgagcaa tctggtgggc ctgcccaaca 120

atatctgtct gcagaagacc tccaaccaga tcctgaagcc caagctgatc tcctatacac 180

tgcctgtggt gggccagtct ggcacctgca tcacagaccc tctgctggcc atggatgagg 240

gctacttcgc ctattctcac ctggagagga tcggctcctg ttctcgcggc gtgagcaagc 300

agcggatcat cggagtggga gaggtgctgg acaggggcga tgaggtgcct tccctgttca 360

tgaccaacgt gtggacacca cccaatccaa acaccgtgta ccactgctct gccgtgtata 420

acaatgagtt ttactacgtg ctgtgcgccg tgagcaccgt gggcgatcct atcctgaact 480

ccacatactg gagcggctcc ctgatgatga ccagactggc cgtgaagcca aagtccaatg 540

gcggcggcta taaccagcac cagctggccc tgagatctat cgagaagggc aggtacgata 600

aagtgatgcc ttatggccca tctggcatca agcagggcga cacactgtac ttccccgccg 660

tgggctttct ggtgaggacc gagttcaagt acaatgactc caactgccct atcacaaagt 720

gtcagtattc taagccagag aattgccgcc tgagcatggg catccggccc aactctcact 780

acatcctgag aagcggcctg ctgaagtata atctgagcga cggcgagaac cctaaggtgg 840

tgtttatcga gatctccgat cagaggctgt ctatcggctc tcccagcaag atctacgact 900

ccctgggcca gcccgtgttc taccaggcct ccttttcttg ggacacaatg atcaagttcg 960

gcgatgtgct gaccgtgaat ccactggtgg tgaactggag aaacaatacc gtgatcagca 1020

ggccaggaca gtcccagtgt cctcgcttta acacatgccc agagatctgt tgggagggcg 1080

tgtacaatga cgccttcctg atcgatcgga tcaactggat ctccgccggc gtgtttctgg 1140

actctaatca gaccgccgag aaccccgtgt tcacagtgtt taaggataat gagatcctgt 1200

acagggcaca gctggcaagc gaggacacca acgcccagaa gaccatcaca aattgcttcc 1260

tgctgaagaa caagatctgg tgtatctccc tggtggagat ctatgacacc ggcgataacg 1320

tgatccggcc aaagctgttt gccgtgaaga tccccgagca gtgcacaggc ggcggtcagg 1380

gcatcctgca ctacgagaag ctgagcaaga tcggcctggt gaagggcgtg accagaaagt 1440

ataagatcaa gtccaaccca ctgacaaagg acatcgtgat caagatgatc cccaacgtga 1500

gcaatatgtc tcagtgtacc ggctctgtga tggagaacta caagacccgc ctgaatggca 1560

tcctgacacc aatcaagggc gccctggaga tctataagaa caatacacac gactgcgtgg 1620

gcgatgtgcg gctggcaggc gtgtgcatgg caggagtggc aatcggaatc gcaaccgcag 1680

cacagatcac agcaggagtg gccctgtatg aggccatgaa gaacgccgac aacatcaata 1740

agctgaagag ctccatcgag agcaccaatg aggccgtggt gaagctgcag gagacagccg 1800

agaagacagt gtacgtgttc acagccctgc aggactatat caacaccaat ctggtgccca 1860

caatcgataa gatcccctgc aagcagaccg agctgtccct ggacctggcc ctgtctaagt 1920

acctgagcga tctgctgttc gtgtttggcc caaacctgca ggaccccgtg tccaattcta 1980

tgacaatcca ggccatctcc caggccttcg gcggcaatta cgagacactg ctgagaacac 2040

tgggctatgc caccgaggac tttgacgatc tgctggagag cgattccatc acaggccaga 2100

tcatctatgt ggatctgtct agctactata tcatcgtgag ggtgtacttc cctatcctga 2160

ccgagatcca gcaggcctat atccaggagc tgctgccagt gagcttcaac aatgacaatt 2220

ccgagtggat ctctatcgtg cccaacttta tcctggtgcg gaacaccctg atcagcaata 2280

tcgagatcgg cttttgcctg atcacaaaga gatccgtgat ctgtaatcag gactacgcca 2340

cccccatgac aaacaatatg agggagtgcc tgaccggctc cacagagaag tgtccccggg 2400

agctggtggt gtcctctcac gtgcctagat tcgccctgtc caacggcgtg ctgtttgcca 2460

attgcatctc tgtgacctgc cagtgtcaga ccacaggaag ggcaatctct cagagcggag 2520

agcagaccct gctgatgatc gataacacca catgtcctac agccgtgctg ggcaatgtga 2580

tcatcagcct gggcaagtac ctgggctccg tgaactataa ttctgaggga atcgcaatcg 2640

gaccacccgt gttcaccgac aaggtggata tcagctccca gatctctagc atgaaccaga 2700

gcctgcagca gtccaaggac tacatcaagg aggcccagcg gctgctggat accgtgaatc 2760

cttctctgaa gctgatgaag cagatcgagg ataagatcga ggagatcctg agcaagatct 2820

atcacatcga gaacgagatc gccaggatca agaagctgat cggagaggca cctggatctg 2880

gttacatccc agaggctccg cgggatggac aggcctacgt gagaaaggac ggcgagtggg 2940

tgctgctgag caccttcctg ggaagcctgg tgcctagggg ctcccaccac caccaccacc 3000

acagcgcctg gtcccaccca cagtttgaga agtgatgagg atcc 3044

<210> 63

<211> 1653

<212> DNA

<213> 人工序列

<220>

<223> 重组尼帕病毒序列

<400> 63

tctagagcca ccatgtactc tatgcagctg gccagctgcg tgaccctgac actggtgctg 60

ctggtgaact ctcagggcat cctgcactac gagaagctga gcaagatcgg cctggtgaag 120

ggcgtgacca gaaagtataa gatcaagtcc aacccactga caaaggacat cgtgatcaag 180

atgatcccca acgtgagcaa tatgtctcag tgtaccggct ctgtgatgga gaactacaag 240

acccgcctga atggcatcct gacaccaatc aagggcgccc tggagatcta taagaacaat 300

acacacgact gcgtgggcga tgtgcggctg gcaggcgtgt gcatggcagg agtggcaatc 360

ggaatcgcaa ccgcagcaca gatcacagca ggagtggccc tgtatgaggc catgaagaac 420

gccgacaaca tcaataagct gaagagctcc atcgagagca ccaatgaggc cgtggtgaag 480

ctgcaggaga cagccgagaa gacagtgtac gtgttcacag ccctgcagga ctatatcaac 540

accaatctgg tgcccacaat cgataagatc ccctgcaagc agaccgagct gtccctggac 600

ctggccctgt ctaagtacct gagcgatctg ctgttcgtgt ttggcccaaa cctgcaggac 660

cccgtgtcca attctatgac aatccaggcc atctcccagg ccttcggcgg caattacgag 720

acactgctga gaacactggg ctatgccacc gaggactttg acgatctgct ggagagcgat 780

tccatcacag gccagatcat ctatgtggat ctgtctagct actatatcat cgtgagggtg 840

tacttcccta tcctgaccga gatccagcag gcctatatcc aggagctgct gccagtgagc 900

ttcaacaatg acgattccga gtggatctct atcgtgccca actttatcct ggtgcggaac 960

accctgatca gcaatatcga gatcggcttt tgcctgatca caaagagatc cgtgatctgt 1020

aatcaggact acgccacccc catgacaaac aatatgaggg agtgcctgac cggctccaca 1080

gagaagtgtc cccgggagct ggtggtgtcc tctcacgtgc ctagattcgc cctgtccaac 1140

ggcgtgctgt ttgccaattg catctctgtg acctgccagt gtcagaccac aggaagggca 1200

atctctcaga gcggagagca gaccctgctg atgatcgata acaccacatg tcctacagcc 1260

gtgctgggca atgtgatcat cagcctgggc aagtacctgg gctccgtgaa ctataattct 1320

gagggaatcg caatcggacc acccgtgttc accgacaagg tggatatcag ctcccagatc 1380

tctagcatga accagagcct gcagcagtcc aaggactaca tcaaggaggc ccagcggctg 1440

ctggataccg tgaatccttc tctgaagctg atgaagcaga tcgaggataa gatcgaggag 1500

atcctgagca agatctatca catcgagaac gagatcgcca ggatcaagaa gctgatcgga 1560

gaggcacctg gaggcctggt gccaaggggc tcccaccacc accaccacca cagcgcctgg 1620

tcccacccac agtttgagaa gtgatgagga tcc 1653

<210> 64

<211> 1979

<212> DNA

<213> 人工序列

<220>

<223> 重组尼帕病毒G序列

<400> 64

tctagaccac catgtactca atgcagctgg cctcttgcgt cacactgaca ctggtcctgc 60

tggtcaactc acagcaccac caccatcatc acggaagcgc ctggtcccac cctcagttcg 120

agaagggagg actggtgccc agaggatccg gcaacagcca gcgccctcag accgagggcg 180

tgagcaatct ggtgggcctg cccaacaata tctgtctgca gaagacctcc aaccagatcc 240

tgaagcccaa gctgatctcc tatacactgc ctgtggtggg ccagtctggc acctgcatca 300

cagaccctct gctggccatg gatgagggct acttcgccta ttctcacctg gagaggatcg 360

gctcctgttc tcgcggcgtg agcaagcagc ggatcatcgg agtgggagag gtgctggaca 420

ggggcgatga ggtgccttcc ctgttcatga ccaacgtgtg gacaccaccc aatccaaaca 480

ccgtgtacca ctgctctgcc gtgtataaca atgagtttta ctacgtgctg tgcgccgtga 540

gcaccgtggg cgatcctatc ctgaactcca catactggag cggctccctg atgatgacca 600

gactggccgt gaagccaaag tccaatggcg gcggctataa ccagcaccag ctggccctga 660

gatctatcga gaagggcagg tacgataaag tgatgcctta tggcccatct ggcatcaagc 720

agggcgacac actgtacttc cccgccgtgg gctttctggt gaggaccgag ttcaagtaca 780

atgactccaa ctgccctatc acaaagtgtc agtattctaa gccagagaat tgccgcctga 840

gcatgggcat ccggcccaac tctcactaca tcctgagaag cggcctgctg aagtataatc 900

tgagcgacgg cgagaaccct aaggtggtgt ttatcgagat ctccgatcag aggctgtcta 960

tcggctctcc cagcaagatc tacgactccc tgggccagcc cgtgttctac caggcctcct 1020

tttcttggga cacaatgatc aagttcggcg atgtgctgac cgtgaatcca ctggtggtga 1080

actggagaaa caataccgtg atcagcaggc caggacagtc ccagtgtcct cgctttaaca 1140

catgcccaga gatctgttgg gagggcgtgt acaatgacgc cttcctgatc gatcggatca 1200

actggatctc cgccggcgtg tttctggact ctaatcagac cgccgagaac cccgtgttca 1260

cagtgtttaa ggataatgag atcctgtaca gggcacagct ggcaagcgag gacaccaacg 1320

cccagaagac catcacaaat tgcttcctgc tgaagaacaa gatctggtgt atctccctgg 1380

tggagatcta tgacaccggc gataacgtga tccggccaaa gctgtttgcc gtgaagatcc 1440

ccgagcagtg cacaggcggc ggcagcggcg gggatatcat taagctgctg aacgaacagg 1500

tgaacaagga gatgcagtca agcaacctgt acatgtctat gtcctcttgg tgctatacac 1560

atagtctgga cggagctggc ctgttcctgt ttgatcacgc agccgaggaa tacgaacatg 1620

caaagaaact gatcattttc ctgaatgaga acaatgtgcc agtccagctg acaagtatct 1680

cagcccccga acacaagttc gaggggctga ctcagatctt tcagaaagct tacgaacacg 1740

agcagcatat tagcgaatcc atcaacaata ttgtggacca cgctatcaag tccaaagatc 1800

atgcaacctt caactttctg cagtggtacg tggccgagca gcacgaggaa gaggtcctgt 1860

ttaaggacat cctggataaa atcgaactga ttggcaacga gaatcatggg ctgtacctgg 1920

ccgatcagta tgtgaagggc attgctaagt cacggaaaag cggaagctga tgaccgcgg 1979

<210> 65

<211> 2951

<212> DNA

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 65

tctagagcca ccatgtactc tatgcagctg gccagctgcg tgaccctgac actggtgctg 60

ctggtgaact ctcagggcat cctgcactac gagaagctga gcaagatcgg cctggtgaag 120

ggcgtgacca gaaagtataa gatcaagtcc aacccactga caaaggacat cgtgatcaag 180

atgatcccca acgtgagcaa tatgtctcag tgtaccggct ctgtgatgga gaactacaag 240

acccgcctga atggcatcct gacaccaatc aagggcgccc tggagatcta taagaacaat 300

acacacgact gcgtgggcga tgtgcggctg gcaggcgtgt gcatggcagg agtggcaatc 360

ggaatcgcaa ccgcagcaca gatcacagca ggagtggccc tgtatgaggc catgaagaac 420

gccgacaaca tcaataagct gaagagctcc atcgagagca ccaatgaggc cgtggtgaag 480

ctgcaggaga cagccgagaa gacagtgtac gtgttcacag ccctgcagga ctatatcaac 540

accaatctgg tgcccacaat cgataagatc ccctgcaagc agaccgagct gtccctggac 600

ctggccctgt ctaagtacct gagcgatctg ctgttcgtgt ttggcccaaa cctgcaggac 660

cccgtgtcca attctatgac aatccaggcc atctcccagg ccttcggcgg caattacgag 720

acactgctga gaacactggg ctatgccacc gaggactttg acgatctgct ggagagcgat 780

tccatcacag gccagatcat ctatgtggat ctgtctagct actatatcat cgtgagggtg 840

tacttcccta tcctgaccga gatccagcag gcctatatcc aggagctgct gccagtgagc 900

ttcaacaatg acaattccga gtggatctct atcgtgccca actttatcct ggtgcggaac 960

accctgatca gcaatatcga gatcggcttt tgcctgatca caaagagatc cgtgatctgt 1020

aatcaggact acgccacccc catgacaaac aatatgaggg agtgcctgac cggctccaca 1080

gagaagtgtc cccgggagct ggtggtgtcc tctcacgtgc ctagattcgc cctgtccaac 1140

ggcgtgctgt ttgccaattg catctctgtg acctgccagt gtcagaccac aggaagggca 1200

atctctcaga gcggagagca gaccctgctg atgatcgata acaccacatg tcctacagcc 1260

gtgctgggca atgtgatcat cagcctgggc aagtacctgg gctccgtgaa ctataattct 1320

gagggaatcg caatcggacc acccgtgttc accgacaagg tggatatcag ctcccagatc 1380

tctagcatga accagagcct gcagcagtcc aaggactaca tcaaggaggc ccagcggctg 1440

ctggataccg tgaatccttc tctgaagctg atgaagcaga tcgaggataa gatcgaggag 1500

atcctgagca agatctatca catcgagaac gagatcgcca ggatcaagaa gctgatcgga 1560

gaggcacctg gatctggtgg aggaggcgga ggcgtgagca atctggtggg cctgcccaac 1620

aatatctgtc tgcagaagac ctccaaccag atcctgaagc ccaagctgat ctcctataca 1680

ctgcctgtgg tgggccagtc tggcacctgc atcacagacc ctctgctggc catggatgag 1740

ggctacttcg cctattctca cctggagagg atcggctcct gttctcgcgg cgtgagcaag 1800

cagcggatca tcggagtggg agaggtgctg gacaggggcg atgaggtgcc ttccctgttc 1860

atgaccaacg tgtggacacc acccaatcca aacaccgtgt accactgctc tgccgtgtat 1920

aacaatgagt tttactacgt gctgtgcgcc gtgagcaccg tgggcgatcc tatcctgaac 1980

tccacatact ggagcggctc cctgatgatg accagactgg ccgtgaagcc aaagtccaat 2040

ggcggcggct ataaccagca ccagctggcc ctgagatcta tcgagaaggg caggtacgat 2100

aaagtgatgc cttatggccc atctggcatc aagcagggcg acacactgta cttccccgcc 2160

gtgggctttc tggtgaggac cgagttcaag tacaatgact ccaactgccc tatcacaaag 2220

tgtcagtatt ctaagccaga gaattgccgc ctgagcatgg gcatccggcc caactctcac 2280

tacatcctga gaagcggcct gctgaagtat aatctgagcg acggcgagaa ccctaaggtg 2340

gtgtttatcg agatctccga tcagaggctg tctatcggct ctcccagcaa gatctacgac 2400

tccctgggcc agcccgtgtt ctaccaggcc tccttttctt gggacacaat gatcaagttc 2460

ggcgatgtgc tgaccgtgaa tccactggtg gtgaactgga gaaacaatac cgtgatcagc 2520

aggccaggac agtcccagtg tcctcgcttt aacacatgcc cagagatctg ttgggagggc 2580

gtgtacaatg acgccttcct gatcgatcgg atcaactgga tctccgccgg cgtgtttctg 2640

gactctaatc agaccgccga gaaccccgtg ttcacagtgt ttaaggataa tgagatcctg 2700

tacagggcac agctggcaag cgaggacacc aacgcccaga agaccatcac aaattgcttc 2760

ctgctgaaga acaagatctg gtgtatctcc ctggtggaga tctatgacac cggcgataac 2820

gtgatccggc caaagctgtt tgccgtgaag atccccgagc agtgcacagg cggcctggtg 2880

cctagaggct ctcaccacca ccatcaccac agcgcctggt cccaccccca gttcgagaag 2940

tgataggatc c 2951

<210> 66

<211> 2933

<212> DNA

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 66

tctagagcca ccatgtactc tatgcagctg gccagctgcg tgaccctgac actggtgctg 60

ctggtgaact ctcagggcat cctgcactac gagaagctga gcaagatcgg cctggtgaag 120

ggcgtgacca gaaagtataa gatcaagtcc aacccactga caaaggacat cgtgatcaag 180

atgatcccca acgtgagcaa tatgtctcag tgtaccggct ctgtgatgga gaactacaag 240

acccgcctga atggcatcct gacaccaatc aagggcgccc tggagatcta taagaacaat 300

acacacgact gcgtgggcga tgtgcggctg gcaggcgtgt gcatggcagg agtggcaatc 360

ggaatcgcaa ccgcagcaca gatcacagca ggagtggccc tgtatgaggc catgaagaac 420

gccgacaaca tcaataagct gaagagctcc atcgagagca ccaatgaggc cgtggtgaag 480

ctgcaggaga cagccgagaa gacagtgtac gtgttcacag ccctgcagga ctatatcaac 540

accaatctgg tgcccacaat cgataagatc ccctgcaagc agaccgagct gtccctggac 600

ctggccctgt ctaagtacct gagcgatctg ctgttcgtgt ttggcccaaa cctgcaggac 660

cccgtgtcca attctatgac aatccaggcc atctcccagg ccttcggcgg caattacgag 720

acactgctga gaacactggg ctatgccacc gaggactttg acgatctgct ggagagcgat 780

tccatcacag gccagatcat ctatgtggat ctgtctagct actatatcat cgtgagggtg 840

tacttcccta tcctgaccga gatccagcag gcctatatcc aggagctgct gccagtgagc 900

ttcaacaatg acaattccga gtggatctct atcgtgccca actttatcct ggtgcggaac 960

accctgatca gcaatatcga gatcggcttt tgcctgatca caaagagatc cgtgatctgt 1020

aatcaggact acgccacccc catgacaaac aatatgaggg agtgcctgac cggctccaca 1080

gagaagtgtc cccgggagct ggtggtgtcc tctcacgtgc ctagattcgc cctgtccaac 1140

ggcgtgctgt ttgccaattg catctctgtg acctgccagt gtcagaccac aggaagggca 1200

atctctcaga gcggagagca gaccctgctg atgatcgata acaccacatg tcctacagcc 1260

gtgctgggca atgtgatcat cagcctgggc aagtacctgg gctccgtgaa ctataattct 1320

gagggaatcg caatcggacc acccgtgttc accgacaagg tggatatcag ctcccagatc 1380

tctagcatga accagagcct gcagcagtcc aaggactaca tcaaggaggc ccagcggctg 1440

ctggataccg tgaatccttc tctgggatct ggttacatcc cagaggctcc gcgggatgga 1500

caggcctacg tgagaaagga cggcgagtgg gtgctgctga gcaccttcct gggaagcggt 1560

ggaggaggcg gaggcgtgag caatctggtg ggcctgccca acaatatctg tctgcagaag 1620

acctccaacc agatcctgaa gcccaagctg atctcctata cactgcctgt ggtgggccag 1680

tctggcacct gcatcacaga ccctctgctg gccatggatg agggctactt cgcctattct 1740

cacctggaga ggatcggctc ctgttctcgc ggcgtgagca agcagcggat catcggagtg 1800

ggagaggtgc tggacagggg cgatgaggtg ccttccctgt tcatgaccaa cgtgtggaca 1860

ccacccaatc caaacaccgt gtaccactgc tctgccgtgt ataacaatga gttttactac 1920

gtgctgtgcg ccgtgagcac cgtgggcgat cctatcctga actccacata ctggagcggc 1980

tccctgatga tgaccagact ggccgtgaag ccaaagtcca atggcggcgg ctataaccag 2040

caccagctgg ccctgagatc tatcgagaag ggcaggtacg ataaagtgat gccttatggc 2100

ccatctggca tcaagcaggg cgacacactg tacttccccg ccgtgggctt tctggtgagg 2160

accgagttca agtacaatga ctccaactgc cctatcacaa agtgtcagta ttctaagcca 2220

gagaattgcc gcctgagcat gggcatccgg cccaactctc actacatcct gagaagcggc 2280

ctgctgaagt ataatctgag cgacggcgag aaccctaagg tggtgtttat cgagatctcc 2340

gatcagaggc tgtctatcgg ctctcccagc aagatctacg actccctggg ccagcccgtg 2400

ttctaccagg cctccttttc ttgggacaca atgatcaagt tcggcgatgt gctgaccgtg 2460

aatccactgg tggtgaactg gagaaacaat accgtgatca gcaggccagg acagtcccag 2520

tgtcctcgct ttaacacatg cccagagatc tgttgggagg gcgtgtacaa tgacgccttc 2580

ctgatcgatc ggatcaactg gatctccgcc ggcgtgtttc tggactctaa tcagaccgcc 2640

gagaaccccg tgttcacagt gtttaaggat aatgagatcc tgtacagggc acagctggca 2700

agcgaggaca ccaacgccca gaagaccatc acaaattgct tcctgctgaa gaacaagatc 2760

tggtgtatct ccctggtgga gatctatgac accggcgata acgtgatccg gccaaagctg 2820

tttgccgtga agatccccga gcagtgcaca ggcggcctgg tgcctagagg ctctcaccac 2880

caccatcacc acagcgcctg gtcccacccc cagttcgaga agtgatagga tcc 2933

<210> 67

<211> 2831

<212> DNA

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 67

tctagagcca ccatgtactc tatgcagctg gccagctgcg tgaccctgac actggtgctg 60

ctggtgaact ctcaggaggg cgtgagcaat ctggtgggcc tgcccaacaa tatctgtctg 120

cagaagacct ccaaccagat cctgaagccc aagctgatct cctatacact gcctgtggtg 180

ggccagtctg gcacctgcat cacagaccct ctgctggcca tggatgaggg ctacttcgcc 240

tattctcacc tggagaggat cggctcctgt tctcgcggcg tgagcaagca gcggatcatc 300

ggagtgggag aggtgctgga caggggcgat gaggtgcctt ccctgttcat gaccaacgtg 360

tggacaccac ccaatccaaa caccgtgtac cactgctctg ccgtgtataa caatgagttt 420

tactacgtgc tgtgcgccgt gagcaccgtg ggcgatccta tcctgaactc cacatactgg 480

agcggctccc tgatgatgac cagactggcc gtgaagccaa agtccaatgg cggcggctat 540

aaccagcacc agctggccct gagatctatc gagaagggca ggtacgataa agtgatgcct 600

tatggcccat ctggcatcaa gcagggcgac acactgtact tccccgccgt gggctttctg 660

gtgaggaccg agttcaagta caatgactcc aactgcccta tcacaaagtg tcagtattct 720

aagccagaga attgccgcct gagcatgggc atccggccca actctcacta catcctgaga 780

agcggcctgc tgaagtataa tctgagcgac ggcgagaacc ctaaggtggt gtttatcgag 840

atctccgatc agaggctgtc tatcggctct cccagcaaga tctacgactc cctgggccag 900

cccgtgttct accaggcctc cttttcttgg gacacaatga tcaagttcgg cgatgtgctg 960

accgtgaatc cactggtggt gaactggaga aacaataccg tgatcagcag gccaggacag 1020

tcccagtgtc ctcgctttaa cacatgccca gagatctgtt gggagggcgt gtacaatgac 1080

gccttcctga tcgatcggat caactggatc tccgccggcg tgtttctgga ctctaatcag 1140

accgccgaga accccgtgtt cacagtgttt aaggataatg agatcctgta cagggcacag 1200

ctggcaagcg aggacaccaa cgcccagaag accatcacaa attgcttcct gctgaagaac 1260

aagatctggt gtatctccct ggtggagatc tatgacaccg gcgataacgt gatccggcca 1320

aagctgtttg ccgtgaagat ccccgagcag tgcacaggcg gcggatctgg ttacatccca 1380

gaggctccgc gggatggaca ggcctacgtg agaaaggacg gcgagtgggt gctgctgagc 1440

accttcctgg gaagcggtgg aggaggcgga ggcgtgagca atctggtggg cctgcccaac 1500

aatatctgtc tgcagaagac ctccaaccag atcctgaagc ccaagctgat ctcctataca 1560

ctgcctgtgg tgggccagtc tggcacctgc atcacagacc ctctgctggc catggatgag 1620

ggctacttcg cctattctca cctggagagg atcggctcct gttctcgcgg cgtgagcaag 1680

cagcggatca tcggagtggg agaggtgctg gacaggggcg atgaggtgcc ttccctgttc 1740

atgaccaacg tgtggacacc acccaatcca aacaccgtgt accactgctc tgccgtgtat 1800

aacaatgagt tttactacgt gctgtgcgcc gtgagcaccg tgggcgatcc tatcctgaac 1860

tccacatact ggagcggctc cctgatgatg accagactgg ccgtgaagcc aaagtccaat 1920

ggcggcggct ataaccagca ccagctggcc ctgagatcta tcgagaaggg caggtacgat 1980

aaagtgatgc cttatggccc atctggcatc aagcagggcg acacactgta cttccccgcc 2040

gtgggctttc tggtgaggac cgagttcaag tacaatgact ccaactgccc tatcacaaag 2100

tgtcagtatt ctaagccaga gaattgccgc ctgagcatgg gcatccggcc caactctcac 2160

tacatcctga gaagcggcct gctgaagtat aatctgagcg acggcgagaa ccctaaggtg 2220

gtgtttatcg agatctccga tcagaggctg tctatcggct ctcccagcaa gatctacgac 2280

tccctgggcc agcccgtgtt ctaccaggcc tccttttctt gggacacaat gatcaagttc 2340

ggcgatgtgc tgaccgtgaa tccactggtg gtgaactgga gaaacaatac cgtgatcagc 2400

aggccaggac agtcccagtg tcctcgcttt aacacatgcc cagagatctg ttgggagggc 2460

gtgtacaatg acgccttcct gatcgatcgg atcaactgga tctccgccgg cgtgtttctg 2520

gactctaatc agaccgccga gaaccccgtg ttcacagtgt ttaaggataa tgagatcctg 2580

tacagggcac agctggcaag cgaggacacc aacgcccaga agaccatcac aaattgcttc 2640

ctgctgaaga acaagatctg gtgtatctcc ctggtggaga tctatgacac cggcgataac 2700

gtgatccggc caaagctgtt tgccgtgaag atccccgagc agtgcacagg cggcctggtg 2760

cctagaggct ctcaccacca ccatcaccac agcgcctggt cccaccccca gttcgagaag 2820

tgataggatc c 2831

<210> 68

<211> 436

<212> PRT

<213> Hendra病毒

<400> 68

Arg Glu Tyr Arg Pro Ile Ser Gln Gly Val Ser Asp Leu Val Gly Leu

1 5 10 15

Pro Asn Gln Ile Cys Leu Gln Lys Thr Thr Ser Thr Ile Leu Lys Pro

20 25 30

Arg Leu Ile Ser Tyr Thr Leu Pro Ile Asn Thr Arg Glu Gly Val Cys

35 40 45

Ile Thr Asp Pro Leu Leu Ala Val Asp Asn Gly Phe Phe Ala Tyr Ser

50 55 60

His Leu Glu Lys Ile Gly Ser Cys Thr Arg Gly Ile Ala Lys Gln Arg

65 70 75 80

Ile Ile Gly Val Gly Glu Val Leu Asp Arg Gly Asp Lys Val Pro Ser

85 90 95

Met Phe Met Thr Asn Val Trp Thr Pro Pro Asn Pro Ser Thr Ile His

100 105 110

His Cys Ser Ser Thr Tyr His Glu Asp Phe Tyr Tyr Thr Leu Cys Ala

115 120 125

Val Ser His Val Gly Asp Pro Ile Leu Asn Ser Thr Ser Trp Thr Glu

130 135 140

Ser Leu Ser Leu Ile Arg Leu Ala Val Arg Pro Lys Ser Asp Ser Gly

145 150 155 160

Asp Tyr Asn Gln Lys Tyr Ile Ala Ile Thr Lys Val Glu Arg Gly Lys

165 170 175

Tyr Asp Lys Val Met Pro Tyr Gly Pro Ser Gly Ile Lys Gln Gly Asp

180 185 190

Thr Leu Tyr Phe Pro Ala Val Gly Phe Leu Pro Arg Thr Glu Phe Gln

195 200 205

Tyr Asn Asp Ser Asn Cys Pro Ile Ile His Cys Lys Tyr Ser Lys Ala

210 215 220

Glu Asn Cys Arg Leu Ser Met Gly Val Asn Ser Lys Ser His Tyr Ile

225 230 235 240

Leu Arg Ser Gly Leu Leu Lys Tyr Asn Leu Ser Leu Gly Gly Asp Ile

245 250 255

Thr Leu Gln Phe Ile Glu Ile Ala Asp Asn Arg Leu Thr Ile Gly Ser

260 265 270

Pro Ser Lys Ile Tyr Asn Ser Leu Gly Gln Pro Val Phe Tyr Gln Ala

275 280 285

Ser Tyr Ser Trp Asp Thr Met Ile Lys Leu Gly Asp Val Asp Thr Val

290 295 300

Asp Pro Leu Arg Val Gln Trp Arg Asn Asn Ser Val Ile Ser Arg Pro

305 310 315 320

Gly Gln Ser Gln Cys Pro Arg Phe Asn Val Cys Pro Glu Val Cys Trp

325 330 335

Glu Gly Thr Tyr Asn Asp Ala Phe Leu Ile Asp Arg Leu Asn Trp Val

340 345 350

Ser Ala Gly Val Tyr Leu Asn Ser Asn Gln Thr Ala Glu Asn Pro Val

355 360 365

Phe Ala Val Phe Lys Asp Asn Glu Ile Leu Tyr Gln Val Pro Leu Ala

370 375 380

Glu Asp Asp Thr Asn Ala Gln Lys Thr Ile Thr Asp Cys Phe Leu Leu

385 390 395 400

Glu Asn Val Ile Trp Cys Ile Ser Leu Val Glu Ile Tyr Asp Thr Gly

405 410 415

Asp Ser Val Ile Arg Pro Lys Leu Phe Ala Val Lys Ile Pro Ala Gln

420 425 430

Cys Ser Glu Ser

435

<210> 69

<211> 1007

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 69

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Gly Ile Leu His Tyr Glu Lys Leu Ser Lys Ile

20 25 30

Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro

35 40 45

Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn Val Ser Asn Met

50 55 60

Ser Gln Cys Thr Gly Ser Val Met Glu Asn Tyr Lys Thr Arg Leu Asn

65 70 75 80

Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile Tyr Lys Asn Asn

85 90 95

Thr His Asp Cys Val Gly Asp Val Arg Leu Ala Gly Val Cys Met Ala

100 105 110

Gly Val Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile Thr Ala Gly Val

115 120 125

Ala Leu Tyr Glu Ala Met Lys Asn Ala Asp Asn Ile Asn Lys Leu Lys

130 135 140

Ser Ser Ile Glu Ser Thr Asn Glu Ala Val Val Lys Leu Gln Glu Thr

145 150 155 160

Ala Glu Lys Thr Val Tyr Val Phe Thr Ala Leu Gln Asp Tyr Ile Asn

165 170 175

Thr Asn Leu Val Pro Thr Ile Asp Lys Ile Pro Cys Lys Gln Thr Glu

180 185 190

Leu Ser Leu Asp Leu Ala Leu Ser Lys Tyr Leu Ser Asp Leu Leu Phe

195 200 205

Val Phe Gly Pro Asn Leu Gln Asp Pro Val Ser Asn Ser Met Thr Ile

210 215 220

Gln Ala Ile Ser Gln Ala Phe Gly Gly Asn Tyr Glu Thr Leu Leu Arg

225 230 235 240

Thr Leu Gly Tyr Ala Thr Glu Asp Phe Asp Asp Leu Leu Glu Ser Asp

245 250 255

Ser Ile Thr Gly Gln Ile Ile Tyr Val Asp Leu Ser Ser Tyr Tyr Ile

260 265 270

Ile Val Arg Val Tyr Phe Pro Ile Leu Thr Glu Ile Gln Gln Ala Tyr

275 280 285

Ile Gln Glu Leu Leu Pro Val Ser Phe Asn Asn Asp Asn Ser Glu Trp

290 295 300

Ile Ser Ile Val Pro Asn Phe Ile Leu Val Arg Asn Thr Leu Ile Ser

305 310 315 320

Asn Ile Glu Ile Gly Phe Cys Leu Ile Thr Lys Arg Ser Val Ile Cys

325 330 335

Asn Gln Asp Tyr Ala Thr Pro Met Thr Asn Asn Met Arg Glu Cys Leu

340 345 350

Thr Gly Ser Thr Glu Lys Cys Pro Arg Glu Leu Val Val Ser Ser His

355 360 365

Val Pro Arg Phe Ala Leu Ser Asn Gly Val Leu Phe Ala Asn Cys Ile

370 375 380

Ser Val Thr Cys Gln Cys Gln Thr Thr Gly Arg Ala Ile Ser Gln Ser

385 390 395 400

Gly Glu Gln Thr Leu Leu Met Ile Asp Asn Thr Thr Cys Pro Thr Ala

405 410 415

Val Leu Gly Asn Val Ile Ile Ser Leu Gly Lys Tyr Leu Gly Ser Val

420 425 430

Asn Tyr Asn Ser Glu Gly Ile Ala Ile Gly Pro Pro Val Phe Thr Asp

435 440 445

Lys Val Asp Ile Ser Ser Gln Ile Ser Ser Met Asn Gln Ser Leu Gln

450 455 460

Gln Ser Lys Asp Tyr Ile Lys Glu Ala Gln Arg Leu Leu Asp Thr Val

465 470 475 480

Asn Pro Ser Leu Lys Leu Met Lys Gln Ile Glu Asp Lys Ile Glu Glu

485 490 495

Ile Leu Ser Lys Ile Tyr His Ile Glu Asn Glu Ile Ala Arg Ile Lys

500 505 510

Lys Leu Ile Gly Glu Ala Pro Gly Ser Gly Tyr Ile Pro Glu Ala Pro

515 520 525

Arg Asp Gly Gln Ala Tyr Val Arg Lys Asp Gly Glu Trp Val Leu Leu

530 535 540

Ser Thr Phe Leu Gly Ser Gly Gly Gly Gly Gly Gly Val Ser Asp Leu

545 550 555 560

Val Gly Leu Pro Asn Gln Ile Cys Leu Gln Lys Thr Thr Ser Thr Ile

565 570 575

Leu Lys Pro Arg Leu Ile Ser Tyr Thr Leu Pro Ile Asn Thr Arg Glu

580 585 590

Gly Val Cys Ile Thr Asp Pro Leu Leu Ala Val Asp Asn Gly Phe Phe

595 600 605

Ala Tyr Ser His Leu Glu Lys Ile Gly Ser Cys Thr Arg Gly Ile Ala

610 615 620

Lys Gln Arg Ile Ile Gly Val Gly Glu Val Leu Asp Arg Gly Asp Lys

625 630 635 640

Val Pro Ser Met Phe Met Thr Asn Val Trp Thr Pro Pro Asn Pro Ser

645 650 655

Thr Ile His His Cys Ser Ser Thr Tyr His Glu Asp Phe Tyr Tyr Thr

660 665 670

Leu Cys Ala Val Ser His Val Gly Asp Pro Ile Leu Asn Ser Thr Ser

675 680 685

Trp Thr Glu Ser Leu Ser Leu Ile Arg Leu Ala Val Arg Pro Lys Ser

690 695 700

Asp Ser Gly Asp Tyr Asn Gln Lys Tyr Ile Ala Ile Thr Lys Val Glu

705 710 715 720

Arg Gly Lys Tyr Asp Lys Val Met Pro Tyr Gly Pro Ser Gly Ile Lys

725 730 735

Gln Gly Asp Thr Leu Tyr Phe Pro Ala Val Gly Phe Leu Pro Arg Thr

740 745 750

Glu Phe Gln Tyr Asn Asp Ser Asn Cys Pro Ile Ile His Cys Lys Tyr

755 760 765

Ser Lys Ala Glu Asn Cys Arg Leu Ser Met Gly Val Asn Ser Lys Ser

770 775 780

His Tyr Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn Leu Ser Leu Gly

785 790 795 800

Gly Asp Ile Thr Leu Gln Phe Ile Glu Ile Ala Asp Asn Arg Leu Thr

805 810 815

Ile Gly Ser Pro Ser Lys Ile Tyr Asn Ser Leu Gly Gln Pro Val Phe

820 825 830

Tyr Gln Ala Ser Tyr Ser Trp Asp Thr Met Ile Lys Leu Gly Asp Val

835 840 845

Asp Thr Val Asp Pro Leu Arg Val Gln Trp Arg Asn Asn Ser Val Ile

850 855 860

Ser Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn Val Cys Pro Glu

865 870 875 880

Val Cys Trp Glu Gly Thr Tyr Asn Asp Ala Phe Leu Ile Asp Arg Leu

885 890 895

Asn Trp Val Ser Ala Gly Val Tyr Leu Asn Ser Asn Gln Thr Ala Glu

900 905 910

Asn Pro Val Phe Ala Val Phe Lys Asp Asn Glu Ile Leu Tyr Gln Val

915 920 925

Pro Leu Ala Glu Asp Asp Thr Asn Ala Gln Lys Thr Ile Thr Asp Cys

930 935 940

Phe Leu Leu Glu Asn Val Ile Trp Cys Ile Ser Leu Val Glu Ile Tyr

945 950 955 960

Asp Thr Gly Asp Ser Val Ile Arg Pro Lys Leu Phe Ala Val Lys Ile

965 970 975

Pro Ala Gln Cys Ser Glu Ser Gly Gly Leu Val Pro Arg Gly Ser His

980 985 990

His His His His His Ser Ala Trp Ser His Pro Gln Phe Glu Lys

995 1000 1005

<210> 70

<211> 1007

<212> PRT

<213> 人工序列

<220>

<223> 重组尼帕病毒F序列

<400> 70

Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu

1 5 10 15

Leu Val Asn Ser Gln Arg Pro Gln Thr Glu Gly Val Ser Asn Leu Val

20 25 30

Gly Leu Pro Asn Asn Ile Cys Leu Gln Lys Thr Ser Asn Gln Ile Leu

35 40 45

Lys Pro Lys Leu Ile Ser Tyr Thr Leu Pro Val Val Gly Gln Ser Gly

50 55 60

Thr Cys Ile Thr Asp Pro Leu Leu Ala Met Asp Glu Gly Tyr Phe Ala

65 70 75 80

Tyr Ser His Leu Glu Arg Ile Gly Ser Cys Ser Arg Gly Val Ser Lys

85 90 95

Gln Arg Ile Ile Gly Val Gly Glu Val Leu Asp Arg Gly Asp Glu Val

100 105 110

Pro Ser Leu Phe Met Thr Asn Val Trp Thr Pro Pro Asn Pro Asn Thr

115 120 125

Val Tyr His Cys Ser Ala Val Tyr Asn Asn Glu Phe Tyr Tyr Val Leu

130 135 140

Cys Ala Val Ser Thr Val Gly Asp Pro Ile Leu Asn Ser Thr Tyr Trp

145 150 155 160

Ser Gly Ser Leu Met Met Thr Arg Leu Ala Val Lys Pro Lys Ser Asn

165 170 175

Gly Gly Gly Tyr Asn Gln His Gln Leu Ala Leu Arg Ser Ile Glu Lys

180 185 190

Gly Arg Tyr Asp Lys Val Met Pro Tyr Gly Pro Ser Gly Ile Lys Gln

195 200 205

Gly Asp Thr Leu Tyr Phe Pro Ala Val Gly Phe Leu Val Arg Thr Glu

210 215 220

Phe Lys Tyr Asn Asp Ser Asn Cys Pro Ile Thr Lys Cys Gln Tyr Ser

225 230 235 240

Lys Pro Glu Asn Cys Arg Leu Ser Met Gly Ile Arg Pro Asn Ser His

245 250 255

Tyr Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn Leu Ser Asp Gly Glu

260 265 270

Asn Pro Lys Val Val Phe Ile Glu Ile Ser Asp Gln Arg Leu Ser Ile

275 280 285

Gly Ser Pro Ser Lys Ile Tyr Asp Ser Leu Gly Gln Pro Val Phe Tyr

290 295 300

Gln Ala Ser Phe Ser Trp Asp Thr Met Ile Lys Phe Gly Asp Val Leu

305 310 315 320

Thr Val Asn Pro Leu Val Val Asn Trp Arg Asn Asn Thr Val Ile Ser

325 330 335

Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn Thr Cys Pro Glu Ile

340 345 350

Cys Trp Glu Gly Val Tyr Asn Asp Ala Phe Leu Ile Asp Arg Ile Asn

355 360 365

Trp Ile Ser Ala Gly Val Phe Leu Asp Ser Asn Gln Thr Ala Glu Asn

370 375 380

Pro Val Phe Thr Val Phe Lys Asp Asn Glu Ile Leu Tyr Arg Ala Gln

385 390 395 400

Leu Ala Ser Glu Asp Thr Asn Ala Gln Lys Thr Ile Thr Asn Cys Phe

405 410 415

Leu Leu Lys Asn Lys Ile Trp Cys Ile Ser Leu Val Glu Ile Tyr Asp

420 425 430

Thr Gly Asp Asn Val Ile Arg Pro Lys Leu Phe Ala Val Lys Ile Pro

435 440 445

Glu Gln Cys Thr Gly Gly Gly Gln Gly Ile Leu His Tyr Glu Lys Leu

450 455 460

Ser Lys Ile Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile Lys

465 470 475 480

Ser Asn Pro Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn Val

485 490 495

Ser Asn Met Ser Gln Cys Thr Gly Ser Val Met Glu Asn Tyr Lys Thr

500 505 510

Arg Leu Asn Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile Tyr

515 520 525

Lys Asn Asn Thr His Asp Cys Val Gly Asp Val Arg Leu Ala Gly Val

530 535 540

Cys Met Ala Gly Val Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile Thr

545 550 555 560

Ala Gly Val Ala Leu Tyr Glu Ala Met Lys Asn Ala Asp Asn Ile Asn

565 570 575

Lys Leu Lys Ser Ser Ile Glu Ser Thr Asn Glu Ala Val Val Lys Leu

580 585 590

Gln Glu Thr Ala Glu Lys Thr Val Tyr Val Phe Thr Ala Leu Gln Asp

595 600 605

Tyr Ile Asn Thr Asn Leu Val Pro Thr Ile Asp Lys Ile Pro Cys Lys

610 615 620

Gln Thr Glu Leu Ser Leu Asp Leu Ala Leu Ser Lys Tyr Leu Ser Asp

625 630 635 640

Leu Leu Phe Val Phe Gly Pro Asn Leu Gln Asp Pro Val Ser Asn Ser

645 650 655

Met Thr Ile Gln Ala Ile Ser Gln Ala Phe Gly Gly Asn Tyr Glu Thr

660 665 670

Leu Leu Arg Thr Leu Gly Tyr Ala Thr Glu Asp Phe Asp Asp Leu Leu

675 680 685

Glu Ser Asp Ser Ile Thr Gly Gln Ile Ile Tyr Val Asp Leu Ser Ser

690 695 700

Tyr Tyr Ile Ile Val Arg Val Tyr Phe Pro Ile Leu Thr Glu Ile Gln

705 710 715 720

Gln Ala Tyr Ile Gln Glu Leu Leu Pro Val Ser Phe Asn Asn Asp Asn

725 730 735

Ser Glu Trp Ile Ser Ile Val Pro Asn Phe Ile Leu Val Arg Asn Thr

740 745 750

Leu Ile Ser Asn Ile Glu Ile Gly Phe Cys Leu Ile Thr Lys Arg Ser

755 760 765

Val Ile Cys Asn Gln Asp Tyr Ala Thr Pro Met Thr Asn Asn Met Arg

770 775 780

Glu Cys Leu Thr Gly Ser Thr Glu Lys Cys Pro Arg Glu Leu Val Val

785 790 795 800

Ser Ser His Val Pro Arg Phe Ala Leu Ser Asn Gly Val Leu Phe Ala

805 810 815

Asn Cys Ile Ser Val Thr Cys Gln Cys Gln Thr Thr Gly Arg Ala Ile

820 825 830

Ser Gln Ser Gly Glu Gln Thr Leu Leu Met Ile Asp Asn Thr Thr Cys

835 840 845

Pro Thr Ala Val Leu Gly Asn Val Ile Ile Ser Leu Gly Lys Tyr Leu

850 855 860

Gly Ser Val Asn Tyr Asn Ser Glu Gly Ile Ala Ile Gly Pro Pro Val

865 870 875 880

Phe Thr Asp Lys Val Asp Ile Ser Ser Gln Ile Ser Ser Met Asn Gln

885 890 895

Ser Leu Gln Gln Ser Lys Asp Tyr Ile Lys Glu Ala Gln Arg Leu Leu

900 905 910

Asp Thr Val Asn Pro Ser Leu Lys Leu Met Lys Gln Ile Glu Asp Lys

915 920 925

Ile Glu Glu Ile Leu Ser Lys Ile Tyr His Ile Glu Asn Glu Ile Ala

930 935 940

Arg Ile Lys Lys Leu Ile Gly Glu Ala Pro Gly Ser Gly Tyr Ile Pro

945 950 955 960

Glu Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys Asp Gly Glu Trp

965 970 975

Val Leu Leu Ser Thr Phe Leu Gly Ser Leu Val Pro Arg Gly Ser His

980 985 990

His His His His His Ser Ala Trp Ser His Pro Gln Phe Glu Lys

995 1000 1005