CN111405907A - 构象稳定的rsv预融合f蛋白 - Google Patents

构象稳定的rsv预融合f蛋白 Download PDF

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CN111405907A
CN111405907A CN201880066038.5A CN201880066038A CN111405907A CN 111405907 A CN111405907 A CN 111405907A CN 201880066038 A CN201880066038 A CN 201880066038A CN 111405907 A CN111405907 A CN 111405907A
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C·马歇尔
M·永多拉
R·马里亚尼
A·宗巴克
S·吉瓦尼
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Abstract

本发明提供了突变RSV F分子，例如那些通过引入一个或多个DT交联，而可以是或稳定处于预融合构象的突变RSV F分子。本发明还提供了制备所述突变RSV F分子的方法、包含所述突变RSV F分子的组合物和使用所述突变RSV F分子的方法，例如用于疫苗接种方法、治疗方法和抗体制备方法。

Description

构象稳定的RSV预融合F蛋白
相关申请的交叉引用
本申请要求2017年8月7日提交的第62/542,247号美国临时专利申请、2018年2月12日提交的第62/629,685号美国临时专利申请、2018年3月8日提交的第62/640,467号美国临时专利申请和2018年5月22日提交的第62/674,791号美国临时专利申请的优先权，其内容各自通过引用整体并入本文。
序列表
本申请包含序列表，该序列表已以ASCII格式的电子方式提交了，通过引用整体并入本文。所述ASCII副本创建于2018年8月3日，命名为Avatar_009_WO1_SL.txt，大小为452739字节。
关于联邦资助研究的声明
本发明是在美国国立卫生研究院授予的AI112124授权号的政府资助下完成。政府对本发明享有一定的权利。
通过引用并入
仅就允许以引用方式并入的司法管辖区而言，本文引用的所有文件的内容通过引用整体并入本文。
背景技术
在美国，呼吸道合胞病毒(RSV)每年感染400～500万儿童，是导致婴儿住院(约150000例住院治疗)的主要原因。在全球范围内，它占1岁以下婴儿死亡的6.7％，仅次于疟疾。此外，它还对其他高危人群，包括老年人和免疫力低下者，构成严重威胁，其中在美国，额外导致大约18万人住院治疗和1.2万人死亡。目前还没有针对FSV的一线治疗方法，目前唯一获批的RSV预防性治疗是被动给药获得许可的单克隆抗体Synagis(帕利珠单抗)，其识别RSV融合(F)蛋白，使严重疾病的发病率仅降低约50％。使用Synagis进行预防性治疗的高昂费用，限制了其仅用于早产儿和24个月以下患有先天性心脏病的婴儿。参见Costello等人的综述“Targeting RSV with Vaccines and Small Molecule Drugs,InfectiousDisorders”，Drug Targets，2012年，第12卷，第2期。开发一种更有效、更理想、更具成本效益的RSV疫苗将具有巨大的价值。
RSV F蛋白是RSV包膜糖蛋白。在自然界中，RSV F蛋白翻译成单一的前体多肽，称为“F0”。F0前体多肽的长度一般为574个氨基酸，其中第1～25位氨基酸包含信号肽。前体多肽F0形成前体三聚体，该前体三聚体被细胞蛋白酶水解切割，产生Pep 27多肽、F1多肽和F2多肽。F2多肽通常含有F0前体的第26～109位氨基酸残基。F1多肽通常包含F0前体的第137～574位氨基酸残基。F1和F2多肽通过二硫键连接形成异二聚体，该异二聚体被称为RSV F“原聚体”。三个这样的原聚体形成RSV F分子的成熟三聚体形式。
已知RSV F蛋白能诱导有效的中和抗体，这些抗体与RSV的防护相关。最近表明了，RSV F蛋白三聚体的预融合构象(在此可称为“预融合F(pre-fusion F)”或“预-F(pre-F)”)是人血清中中和活性的主要决定因素。此外，迄今为止分离到最有效的中和抗体(nAb)仅与预融合构象特异性结合。然而，可溶性pre-F高度不稳定，很容易转变为融合后构象，限制了其作为疫苗免疫原的用途。
稳定在其预融合构象的RSV F蛋白可能具有重要价值，提供候选RSV疫苗免疫原。
在McLellan等人，2013，Science，340，p.1113-1117中，描述了处于预融合构象的RSV F蛋白(与有效的中和Ab-D25结合)的晶体结构，其通过引用整体并入本文。
为了尝试稳定化RSV F的pre-F构象，人们已经研发了几种不同的方法。例如，前述Marshall等人在RSV F蛋白的某些特定位置，引入“至酪氨酸”的点突变和二酪氨酸(DT)交联。参见国际专利申请PCT/US2014/048086。其他方法包括在RSV F蛋白的某些特定位置，引入“至半胱氨酸”的突变、二硫键和/或空腔填充氨基酸替换。参见美国专利第9,738,689号、美国专利第9,950,058号，或McLellan等人(2013)Science342:592-598。
发明内容
本发明提供了一些新的发展和改进，超越了前述Marshall等人在专利申请PCT/US2014/048086中工作，包括但不限于，提供PCT/US2014/048086中未描述的，以及相比PCT/US2014/048086中描述的分子，和相比其他RSV F突变体和RSV F候选免疫原，具有改进特性的一些新的突变RSV F分子。如本专利公开的实施例部分所示，当使用公认的临床前动物模型，将这些新的突变RSV F分子施用于动物体内时，它们具有高度免疫原性。
在一些实施方式中，本发明提供了突变RSV F分子，其包含在第428位氨基酸处突变为酪氨酸(根据标准惯例缩写为“Tyr”或“Y”)的点突变，即“428Y突变”。如本专利公开的实施例部分中进一步所述，相比于其他相同但包含427Y突变而不是428Y突变的突变RSV F分子，包含这种428Y突变的突变RSV F分子(称为“428Y突变体”)具有改进的特性。这些改进的特性包括：(i)疫苗接种后，血清中和滴度增加约5倍；(ii)抗原概况得到显著改善，其通过对抗原位点IV-V的特异性抗体和对预融合特定抗原位点
Figure BDA0002444986400000021
的特异性抗体的结合测定的；和，(iii)相比于六聚体复合物，RSV-F三聚体复合物的产量显著增加。在这些发现的基础上，本发明提供了各种新的且得到改进的突变RSV F分子，包括但不限于，成熟的RSV F三聚体，通过一个或多个DT交联而在构象上被锁定为预融合构象的成熟RSV F三聚体，其各种前体，及其各种组分(包括F1和F2多肽和原聚体)。本发明还提供了所述突变RSV F分子的氨基酸序列，编码所述突变RSV F分子的核苷酸序列，包含所述核苷酸序列的载体，包含和/或表达所述核苷酸序列或载体的细胞，制备所述突变RSV F分子的方法，以及使用所述突变RSVF分子的方法——包括但不限于，在体内用于抗RSV的疫苗接种和用作抗体产生的免疫原。
因此，在一个实施方式中，本发明提供了突变RSV F分子，其包含在第428位氨基酸处突变为酪氨酸的点突变(即428Y突变)，或在对应于第428位的氨基酸位置处(例如，通过比对和/或使用SEQ ID NO.1的氨基酸编号来确定)突变为酪氨酸的点突变。在一些实施方式中，所述突变RSV F分子是或包含RSV F单体或原聚体，每一单体或原聚体均包含428Y突变。在一些实施方式中，所述突变RSV F分子是或包含RSV F三聚体(例如，成熟RSV F三聚体)，每一三聚体包含三个428Y突变。
在一些实施方式中，上述包含428Y突变的突变RSV F分子还包含在第226位氨基酸处突变为酪氨酸的点突变(即226Y突变)，或在对应于第226位的氨基酸位置处(例如，通过比对和/或使用SEQ ID NO.1的氨基酸编号来确定)突变为酪氨酸的点突变。在一些实施方式中，所述突变RSV F分子是或包含RSV F单体或原聚体，每一单体或原聚体均包含428Y突变和226Y突变。在一些实施方式中，所述突变RSV F分子是或包含RSV F三聚体(例如，成熟RSV F三聚体)，每一三聚体均包含三个428Y突变和三个226Y突变。
在一些实施方式中，上述包含428Y突变的突变RSV F分子还包含在第185位氨基酸处突变为酪氨酸的点突变(即185Y突变)，或在对应于第185位的氨基酸位置处(例如，通过比对和/或使用SEQ ID NO.1的氨基酸编号来确定)突变为酪氨酸的点突变。在一些实施方式中，所述突变RSV F分子是或包含RSV F单体或原聚体，每一单体或原聚体均包含428Y突变和185Y突变。在一些实施方式中，所述突变RSV F分子是或包含RSV F三聚体(例如，成熟RSV F三聚体)，每一三聚体均包含三个428Y突变和三个185Y突变。
在一些实施方式中，上述包含428Y突变的突变RSV F分子还包含：(a)在第226位氨基酸处突变为酪氨酸的点突变(即226Y突变)，或在对应于第226位的氨基酸位置处(例如，通过比对和/或使用SEQ ID NO.1的氨基酸编号来确定)突变为酪氨酸的点突变；和，(b)在第185位氨基酸处突变为酪氨酸的点突变(即185Y突变)，或在对应于第185位的氨基酸位置处(例如，通过比对和/或使用SEQ ID NO.1的氨基酸编号来确定)突变为酪氨酸的点突变。在一些实施方式中，所述突变RSV F分子是或包含RSV F单体或原聚体，每一单体或原聚体均包含428Y突变、226Y突变和185Y突变。在一些实施方式中，所述突变RSV F分子是或包含RSV F三聚体(例如，成熟RSV F三聚体)，每一三聚体均包含三个428Y突变、三个226Y突变和三个185Y突变。
上述和本文其他地方描述的各种突变RSV F分子各自也可以包含各种其他突变。
在一些实施方式中，本文所述的突变RSV F分子还包括一个或多个额外突变为酪氨酸的突变——例如在国际专利申请PCT/US2014/048086(公开号WO/2015/013551)中描述的一个或多个突变为酪氨酸的突变，其内容通过引用并入本文。
在一些实施方式中，本文所述的突变RSV F分子还包含一个或多个突变为半胱氨酸的突变，例如一个或多个或美国专利第9,738,689号、美国专利第9,950,058号或McLellan等人(2013)Science 342:592-598中描述的那些，其各自通过引用并入本文。在一些这类实施方式中，RSV F分子包含所谓的“DS”突变——如美国专利第9,738,689号、美国专利第9,950,058号或McLellan等人(2013)Science 342:592-598所述。例如，在一些实施方式中，RSV F分子包含155C突变、290C突变，或155C和290C突变两者。
在一些实施方式中，本文所述的突变RSV F分子还包含一个或多个空腔填充氨基酸替换，例如一个或多个或美国专利第9,738,689号、美国专利第9,950,058号或McLellan等人(2013)Science 342:592-598中描述的那些，其各自通过引用并入本文。在一些这类实施方式中，RSV F分子包含所谓的“Cav1”突变——如美国专利第9,738,689号、美国专利第9,950,058号或McLellan等人(2013)Science 342:592-598所述。例如，在一些实施方式中，RSV F分子包含S190F空腔填充突变、V207L空腔填充突变，或S190F和V207L空腔填充突变两者。
在一些实施方式中，本文所述的突变RSV F分子还包含异源三聚化结构域。在一些这类实施方式中，三聚化结构域是折叠子(foldon)结构域。
在一些实施方式中，本文所述的突变RSV F分子还包括一个或多个标签，其可用于检测和/或纯化RSV F分子。在一些实施方式中，这些标签可以是可切割的标签。在一些这类实施方式中，所述标签为His标签、Strep标签或StrepII标签。
上述和本文其他地方描述的各突变RSV F分子可以以膜结合或可溶性(即非膜结合)形式提供。在一些实施方式中，膜结合形式包括天然存在的RSV F蛋白的跨膜和胞质结构域——其细节(包括序列)在本专利公开的具体实施方式部分中提供。在一些实施方式中，膜结合形式可包括其他跨膜和胞质结构域——即，不是RSV F蛋白天然固有的。在一些实施方式中，使用本文所述的突变RSV F分子的可溶性(即非膜结合)形式。在RSV F分子用作药物组合物的组分——例如用作预防RSV的疫苗时，可溶性形式可能特别有用。如本专利公开的具体实施方式部分中进一步描述的，本文所述的突变RSV F分子的这种可溶性型式可以通过例如移除跨膜和胞质结构域来产生。如本专利公开的具体实施方式部分中进一步描述的，在一些这类实施方式中，可以添加异源序列，来替换跨膜和胞质结构域，例如异源三聚化结构域，例如折叠子(foldon)结构域。
上述和本文其他地方描述的各突变RSV F分子可以以成熟RSV F三聚体的形式提供，其中成熟RSV F三聚体包含一个或多个DT交联并且在构象上锁定为其pre-F构象。这种构象锁定的RSV F分子是通过进行DT交联反应制得的，如本申请的具体实施方式和实施例部分所述，和/或如国际专利申请PCT/US2014/048086(公开号WO/2015/013551)所述，其内容通过引用并入本文。
在一些实施方式中，本发明提供了如本文所述的突变RSV F分子，其包含至少一个DT交联。在一些实施方式中，本发明提供了如本文所述的三聚体突变RSV F分子，其包含至少三个DT交联。在一些实施方式中，本发明提供了如本文所述的三聚体突变RSV F分子，其包含至少六个DT交联。
在一些实施方式中，本发明提供了如本文所述的突变RSV F分子，其包含至少一个DT交联，其中至少一个DT交联的至少一个酪氨酸通过突变为酪氨酸的点突变引入。在一些实施方式中，本发明提供了如本文所述的突变三聚体RSV F分子，其包含至少三个DT交联，其中至少三个DT交联的每一个中的至少一个酪氨酸通过突变为酪氨酸的点突变引入。
例如，在一些实施方式中，在第198位残基处的酪氨酸(通常为天然存在的酪氨酸)和第226位残基处引入的酪氨酸(即由226Y突变产生)之间，引入DT交联——形成分子内198Y-226Y DT交联。这样产生了包含三个分子内DT交联的RSV F三聚体。
在一些实施方式中，在第185位残基处引入的酪氨酸(即由185Y突变产生)和第428位残基处引入的酪氨酸(即由428Y突变产生)之间，引入DT交联——形成185Y-428Y分子间DT交联。这样产生了包含三个分子间DT交联的RSV-F三聚体。
在一些实施方式中，引入198Y-226Y分子内DT交联和185Y-428Y分子间DT交联两者。这样产生了包含六个DT交联的RSV-F三聚体——三个分子内DT交联和三个分子间DT交联。
在一些实施方式中，本发明提供了包含上述或本文其它地方描述的一种或多种突变RSV F分子的组合物。在一些这类实施方式中，所述组合物是药物组合物——即，其组分适合于施用予活体受试者。在一些这类实施方式中，所述药物组合物包含一种或多种佐剂。示范性佐剂包括但不限于明矾(alum)佐剂。在一些实施方式中，所述药物组合物包括载剂。在一些实施方式中，所述药物组合物包括免疫刺激剂。在一些实施方式中，所述组合物是RSV疫苗或构成RSV疫苗的一部分，或可用于疫苗接种方法。
在一些实施方式中，本发明提供了编码上述和本文其他地方描述的各种不同的突变RSV F分子的核酸分子。在一些实施方式中，本发明提供了包含所述核酸分子的载体。在一些实施方式中，本发明提供了包含所述核酸分子或所述载体的细胞。
在一些实施方式中，本发明提供了用于在受试者中治疗或预防RSV的方法。在一些实施方式中，本发明提供了给受试者接种RSV疫苗的方法。在一些实施方式中，本发明提供了在受试者中引发产生RSV中和抗体的方法。这些方法均包括对受试者施用有效量的本文所述的突变RSV F分子，或有效量的包含所述突变RSV F分子的药物组合物。在一些这类实施方式中，受试者是非人类哺乳动物。例如，在一些实施方式中，受试者是用于进行临床前研究的非人类哺乳动物，例如啮齿动物(例如小鼠或棉鼠)或非人类灵长类动物。在一些实施方式中，受试者是人类。在受试者是人类的实施方式中，人类受试者可以是任何年龄。在一些实施方式中，人类受试者是婴儿。在一些实施方式中，人类受试者是儿童。在一些实施方式中，人类受试者的年龄小于24个月。在一些实施方式中，人类受试者是成年人。在一些实施方式中，人类受试者的年龄大于50岁。在一些实施方式中，人类受试者的年龄大于60岁。
在一些实施方式中，本发明提供了使用本文所述的突变RSV F分子作为免疫原，制备抗RSV F抗体的方法。所述抗体可用于多种应用，包括研究应用和治疗应用。例如，在一些实施方式中，该方法包括将本文所述的突变RSV F分子，施用于制备抗体的动物受试者，例如小鼠或兔子。在一些实施方式中，受试者是已经经过基因改造以允许产生完全人类抗体的动物。在其它实施方式中，本文所述的突变RSV F分子可在其他用于抗体制备的系统中用作免疫原，其中其他用于抗体制备的系统包括但不限于文库筛选方法，例如噬菌体展示筛选方法。
本发明的这些和其他方面在本专利申请的具体实施方式、实施例、权利要求书、附图/图和附图说明部分中作了进一步说明——所有这些部分旨在相互结合阅读。此外，本领域技术人员将理解，在本发明上述和本专利公开的其他地方描述的各种实施方式可以以各种不同的方式组合，并且这种组合都在本发明的范围内。
附图说明
图1用于在哺乳动物细胞中表达本文所述RSV F分子的示例性核酸载体。
图2包含198Y-226Y DT交联(“设计1”)和185Y-428Y DT交联(设计2)的突变RSV F分子的示意图。表明抗原位点
Figure BDA0002444986400000051
IV和V与分子结构有关。
图3A-B图3A-在进行DT交联反应后，在2周内，在4℃，利用D25(结合位点
Figure BDA0002444986400000052
的预融合特异性mAb)，通过ELISA测定通过198Y和226Y之间的分子内交联(“设计1”)引入的稳定性。图3B-通过蛋白印迹(Western blotting)分析185Y和428Y之间的分子间DT键的形成(“设计2”)，并与WT进行比较(莫维珠单抗为一抗)。F1蛋白移向三聚体(TM)的大小。
图4用于制备DT交联的AVR02的示例性方案示意图。
图5A-B通过ELISA，比较DS-Cav1、428Y RSV F突变体(AVR02)的未交联型式和428Y突变体(DT-AVR02)的DT交联型式的构象完整性，其中利用莫维珠单抗进行标准化，使用结合抗原位点IV/V的抗体(图5A)和结合位点
Figure BDA0002444986400000053
的抗体(图5B)来评估构象完整性。
图6A-C在100小时37℃热激后，位点
Figure BDA0002444986400000054
的抗原性。图6A在4℃和37℃下孵育后，5C4(位点
Figure BDA0002444986400000055
)与428Y RSV F突变体(AVR02)和428Y RSV F突变体的DT交联型式(DT-AVR02)保留的结合的比较。图6B在37℃下孵育100小时后，5C4和D25与DS-Cav1和DT-AVR02保留的结合。每对中的左条形柱为5C4。每对中的右条形柱是D25。图6C在4℃，5周后，5C4(位点
Figure BDA0002444986400000056
)与428YRSV F突变体(AVR02)保留的结合。
图7DT交联的428Y RSV F突变体(DT-AVR02或DT-preF)在小鼠体内的效果。中和滴度。用明矾负载的DSCAV1或DT-AVR02进行疫苗接种的动物的RSV-海参荧光素酶(RenillaLuc)中和滴度。
图8示例性疫苗接种流程的示意图。
图9DT交联的428Y RSV F突变体(称为DT-AVR02或DT-preF)在棉鼠体内的效果。第+39天，含2％铝胶佐剂的DT交联的428Y RSV F突变体，对鼻冲洗液中RSV/A/Tracy滴度的影响。显示了每个所示对照组和处理组的RSV滴度。
图10DT交联的428Y RSV F突变体(DT-AVR02/DT-preF)在棉鼠体内的效果。第+39天，含2％铝胶佐剂的DT交联的428Y RSV F突变体，对肺灌洗液中RSV/A/Tracy滴度的影响。显示了每个所示对照组和处理组的RSV滴度。
图11DT交联的428Y RSV F突变体(DT-AVR02/DT-preF)在棉鼠体内的效果。含2％铝胶佐剂的DT-preF对RSV/A/Tracy血清中和抗体生成的影响。
图12DT交联428Y RSV F突变体(DT-AVR02/DT-preF)在棉鼠体内的效果。含2％铝胶佐剂的DT-preF对RSV/B/1853交叉反应中和抗体生成的影响。
图13A-D在第428位(428Y)而不是第427位(447Y)的酪氨酸替换，显著改善了RSV F突变体的抗原概况。用链霉亲和素纯化后，可溶性427Y(DT-Cav1)突变体(图13A-B)或428Y(DT-AVR02)突变体(图13C-D)进行DT交联，纯化，并使用所示mAb进行抗原性分析。ELISA使用莫维珠单抗对总蛋白标准化，并在Ni-NTA涂布板上进行。DSCav1用作阳性对照。用两种构象抗体探查预融合结构；对于位点
Figure BDA0002444986400000061
特异性的mAb，结合在抗原位点IV/V之间的预融合特异性mAb。
图14A-C尺寸排除色谱(SEC)和SDS-PAGE分析显示了，DT交联的427Y RSV F突变体(DT-Cav1)和DT交联的428Y RSV F突变体(DT-AVR02)的概况明显不同。显示了，在二酪氨酸交联反应后，立即得到的所示RSV F突变体的尺寸排除色谱图谱(427Y/DT-Cav1图14A左上，428Y/DT-AVR02图14B左下)。428Y突变在交联反应后使高阶种类显著减少。在还原和变性条件下，用SDS-PAGE凝胶分离最终产物，随后进行考马斯染色，如图14C(右)所示。箭头指出了高阶种类(427Y/DT-Cav1)和交联三聚体种类(428Y/DT-AVR02)。
图15A-B接种DT交联428Y RSV F突变体(DT-AVR02)的动物的血清中和滴度，显著高于接种DT交联427Y RSV F突变体(DT-Cav1)的动物。按初始免疫:加强免疫方案，用10μg(微克)的DS-Cav1对照(基准比较物)或所示DT交联分子(图15A(左)的427Y/DT-Cav1和图15B(右)的428Y/DT-AVR02)，对动物进行接种。加强免疫后得到血清，热灭活，然后用RSV-海肾(Renilla)荧光素酶报告病毒得到中和滴度。所示的中和滴度为5只动物/组的平均值，并计算为抑制50％荧光素酶活性的血清稀释度的倒数。
图16A-B含有蔗糖的配方减少了RSV-F聚集体的形成。用DT交联的428Y突变体(DT-AVR02)进行实验。最终浓缩后，进行分析尺寸排除色谱(SEC)。如图16A所示，识别到三个峰——其中峰C为三聚体，峰A和峰B为聚集体。在纯化步骤的洗脱过程中，含有10％蔗糖的DT-AVR02分子配方显得能够减少聚集体的形成。如图16B所示，用10％蔗糖配制的样品中，峰C(三聚体)仍然存在，但峰A和峰B(聚集体)不明显。
具体实施方式
本发明在某种程度上提供了突变RSV F分子，该突变RSV F分子包含一个或多个突变为酪氨酸的突变，可通过或是通过引入一个或多个DT交联而稳定处于预融合构象。本发明还提供编码该突变RSV F分子的核酸分子、制备该突变RSV F分子的方法、包含该突变RSVF分子的组合物以及使用该突变RSV F分子的方法，包括但不限于接种方法、治疗方法，以及抗体制备方法。
定义
除非本文中另有明确定义，否则本发明中使用的技术和科学术语具有本领域普通技术人员通常理解的含义，和/或其含义可从使用术语的上下文中明确。下面定义了几个术语。其他术语在本专利公开文本其他地方有定义。
除非上下文另有明确规定，否则如本说明书和所附权利要求书所用，单数形式“一(a)”、“一(an)”和“该/所述/上述(the)”包含复数指称。术语“一(a)a”(或“一(an)”)以及术语“一个或多个(一种或多种)”和“至少一个(至少一种)”可以互换使用。
此外，“和/或”将被视为两个指定特征或组件中的每一个，在包括或不包括另一个特征或组件的情况下的具体公开。因此，“A和/或B”等短语中使用的“和/或”一词意在包括A和B，A或B，A(单独)，和B(单独)。同样，“A、B和/或C”等短语中使用的“和/或”一词意在包括A、B和C；A、B或C；A或B；A或C；B或C；A和B；A和C；B和C；A(单独)；B(单独)；C(单独)。
单位、前缀和符号以国际单位制(SI)接受的形式表示。本文提供的数字范围包括定义该范围的数字。
如本说明书所用，术语“(大)约”和“大概/近似”，当用于数值时，指所示值的+或-20％的范围。
如本文所使用，术语“示例性”是指用作实例、示例或举例说明。
如本文所用，术语“RSV F分子”指RSV F蛋白的所有形式，包括F1多肽和F2多肽，即，包括F0前体多肽、F0前体多肽的三聚体、RSV F原聚体和成熟RSV F三聚体——无论是膜结合还是可溶性。如本文所用，术语“突变RSV F分子”指含有一个或多个人工引入/人为突变的RSV F分子。
如本文所用，术语“F1多肽”是指包含RSV F F0前体序列的第137～513位氨基酸残基的多肽。第137～513位氨基酸残基不包括RSV F跨膜和胞质结构域。在一些实施方式中，F1多肽还可包括RSV F跨膜和胞质结构域(位于RSV F F0前体序列的第514～574位残基内)。
如本文所用，术语“F2多肽”是指包含RSV F F0前体序列的第26～109位氨基酸残基的多肽。
除非另有说明，否则如本文所用，术语“蛋白质”和“多肽”可互换使用。如本文所用，术语“蛋白质复合物”是指两个或多个蛋白质或蛋白质亚基(例如两个或多个单体或原聚体)的组装体。除非另有说明，否则本文中，与蛋白质或多肽有关的所有描述同样适用于蛋白质复合物，反之亦然。
如本文所用，术语“核酸分子”、“核酸序列”和“核苷酸序列”可互换使用。
如本文所用，术语“稳定”和“锁定”可互换使用，例如关于交联在将RSV F蛋白稳定或锁定在其预融合构象中的作用。这些术语不需要100％的稳定性。更确切地讲，这些术语表示得到提高或增强的稳定性的程度。例如，在一些实施方式中，当术语“稳定”用于RSV F蛋白交联于其预融合构象时，该术语表示，预融合构象的稳定性高于在这种交联之前或没有这种交联的情况。稳定性和相对稳定性，可通过本申请的其他部分所述的各种方式进行测量，例如基于RSV预融合构象的半衰期进行测量。稳定性的提高或增加可在任何程度上有益于预期应用，或对预期应用具有重要意义。例如，在一些实施方式中，稳定性可增加约10％、25％、50％、100％、200％(即2倍)、300％(即3倍)、400％(即4倍)、500％(即5倍)、1000％(即10倍)或更多。
如本文所用，术语“佐剂”是指能够增强、加速或延长，机体对免疫原或免疫原性组合物(如疫苗)的免疫应答的物质。
如本文所用，术语“DS-Cavl”是指McLellan等人，Science，342(6158)，592-598，2013中描述的突变RSV-F蛋白——其包括S155C、S290C、S190F和V207L突变。
如本文所用，术语“预融合构象”是指RSV F分子的，可被预融合特异性抗体特异性结合的结构构象。
如本文所用，术语“预融合特异性抗体”是指，与处于其预融合构象的RSV F分子特异性结合，但不与处于其融合后构象的RSV F蛋白结合的抗体。预融合特异性抗体包括但不限于D25、AM22、5C4和AM14抗体。
如本文所用，术语“AM14”是指WO 2008/147196A2中所述的抗体。
如本文所用，术语“AM22”是指WO 2011/043643A1中述的抗体。
如本文所用，术语“D25”是指WO 2008/147196A2中所述的抗体。
如本文所用，术语“5C4”是指McLellan等人，2010,Nat.Struct.Mol.Biol.,Feb 17(2):248-50)中所述的抗体。McLellan et al.(Science 340:1113-1117(2013))。
突变RSV-F分子
RSV融合蛋白或“F”蛋白是呼吸道合胞病毒的包膜糖蛋白。在自然界中，RSV F蛋白翻译成单一的前体多肽(称为F0)。F0前体多肽的长度一般为574个氨基酸。F0前体的第1～25位氨基酸通常包含信号肽。前体多肽F0形成前体三聚体，该前体三聚体通常被一种或多种细胞蛋白酶，在保守的弗林(furin)共有切割位点处进行蛋白质水解，产生Pep 27多肽、F1多肽和F2多肽。Pep 27多肽(通常为F0前体的第110～136位氨基酸)被切除，不构成成熟RSV F三聚体的一部分。F2多肽(在本文中可替换地称为“F2”或“F2区域”)通常由F0前体的第26～109位氨基酸残基组成。F1多肽(在本文中可替换地称为“F1”或“F1区域”)通常由F0前体的第137～574位氨基酸残基组成，并且包括胞外区域(通常是第137～524位残基)、跨膜结构域(通常是第525～550位残基)和胞质结构域(通常是第551-574位残基)。F1和F2多肽通过二硫键连接形成异二聚体，称为RSV-F“原聚体”。三个这样的原聚体形成成熟的RSV-F三聚体——因此其是三个原聚体的同三聚体。在自然界中，成熟RSV-F三聚体通常是膜结合的。然而，可以通过去除跨膜和胞质区域，来制备成熟RSV-F三聚体的可溶(即非膜结合)型式。例如，通过在第513位氨基酸处截断RSV F蛋白(即，通过去除第514位以后的氨基酸)，可以转变成可溶形式。
在自然界中，成熟RSV-F三聚体介导病毒和细胞膜的融合。成熟RSV-F三聚体的预融合构象(其在本文中可称为“pre-F”)高度不稳定(亚稳定)。然而，一旦RSV病毒与细胞膜对接，RSV-F蛋白三聚体就会发生一系列构象变化，并转变为高度稳定的融合后(“后-F(post-F)”)构象。已知成熟RSV F蛋白能诱导与RSV防护相关的有效中和抗体(“nAb”)。例如，用RSV-F蛋白免疫，能够诱导对人类有防护作用的nAb(如帕利珠单抗)。在RSV-F蛋白的融合后形式上，存在多个中和表位(位点I、II和IV)。但最近，Magro等人表明，将人血清与处于其融合后构象的RSV F蛋白孵育，没有耗尽对F蛋白的大部分中和活性，这表明存在预融合构象特有的中和抗原位点(Magro et al.2012,PNAS 109(8):3089)。通过x射线晶体学，绘制了由帕利珠单抗(Synagis)、莫维珠单抗(Numax)识别的表位，以及最近发现的101F单克隆抗体(McLellan et al.,2010,J.Virol.,84(23):12236-44l；和McLellan et al.,2010,Nat.Struct.Mol.Biol.,Feb 17(2):248-50)识别的表位。McLellan等人(Science340:1113-1117(2013))解析了处于其预融合构象的F蛋白的结构，揭示了一种新的中和表位——位点
Figure BDA0002444986400000081
——仅展示在预融合构象中，并且一系列抗体(例如5C4)与其结合，中和能力比Synagis和Numax高50倍。相应地，越来越多的证据表明，处于这种预融合构象并展示位点
Figure BDA0002444986400000082
的RSV疫苗免疫原，能够引发有效的预防作用。然而，已证明RSV-F蛋白预融合构象的高度不稳定(亚稳定)特性，是研制这种疫苗的重要障碍。基于对McLellan等人的预融合和融合后RSV F结构的比较，F蛋白中似乎有两个区域在构象上发生了很大的变化
Figure BDA0002444986400000083
这些区域位于F1亚基的N-末端和C-末端(分别为第137～216位残基和第461～513位残基)。在RSVF蛋白的晶体结构中，F1的C-末端残基可以通过添加foldon三聚化结构域，而稳定处于预融合构象，其中RSV F蛋白通过与位点
Figure BDA0002444986400000084
表位结合的D25抗体，而保持在其预融合构象。为了稳定F1的N-末端区域，McLellan等人发现，抗体D25的结合足以进行晶体学研究。然而，为了生产疫苗免疫原，需要替代的稳定化方案，例如那些不需要RSV F蛋白与大抗体分子结合的方案。已经尝试过的一种替代方法，涉及在F1的N-末端附近，引入成对的半胱氨酸突变(用于二硫键形成)和空腔填充突变(参见McLellan等人(2013)Science 342:592-598描述的DS-Cav1 RSV F蛋白变体，其通过引用整体并入本文)。然而，这些变体的晶体学分析表明，结构仅部分处于预融合构象。因此，需要对RSV-F蛋白进行额外设计，以获得用于临床疫苗开发的免疫原。
本发明提供了，将RSV F蛋白稳定在其预融合构象的一些替代方法——基于在RSVF分子中的特定位置，引入一个或多个“突变为酪氨酸”的突变，和一个或一个或多个DT交联。
本专利公开的表1和序列表部分提供了几个示例性RSV F和突变RSV F分子的氨基酸序列。表1中提供的大多数序列显示为“F0”序列——即，这些序列包括存在于F0前体中，但不存在于成熟RSV F蛋白中的信号肽和pep27肽。类似地，表1中提供的多个序列包含天然的跨膜和胞质结构域，在一些实施方式中，可以移除这些结构域，以形成可溶型式的成熟RSV三聚体。因此，这些示例性突变RSV分子的最终/成熟型式(即，可能是经DT交联的型式)通常不包含表1中的序列所示的所有氨基酸。然而，这些示例性突变RSV分子的最终/成熟型式将包含这些序列的F2区域和至少一部分F1区域。通常，这些示例性突变RSV分子的最终/成熟型式将包含这些序列的第26～109位氨基酸残基和第137～513位氨基酸残基。应注意，在本文中，提及具有特定示例性氨基酸序列的RSV F分子的所有实施方式中，要考虑F0全序列或其第26～109位氨基酸残基和第137～513位氨基酸残基。
在本专利公开中，当RSV F分子中特定氨基酸位置/残基用其氨基酸残基编号(例如，第428位氨基酸残基)来指代时，除非另有说明，该氨基酸编号是用于本申请序列表和表1(参见，例如，SEQ ID NOs.1～91)中提供的RSV F氨基酸序列的编号。这与本领域在描述RSV F序列时通常使用的编号系统相同。然而应注意，本领域技术人员应理解，可以使用不同的编号系统。例如，如果与SEQ ID NO:1～91中任何一个相比，添加或移除了额外的氨基酸残基。同样，应理解，当特定氨基酸残基用其编号来指代时，描述不仅限于当从给定氨基酸序列的起始位置进行计数时精确位于该编号位置的氨基酸，而且还指代任何和所有RSVF序列中“对应”的氨基酸残基——即使该残基不在给定分子中相同的精确编号位置，例如，如果RSV序列短于或长于SEQ ID NO.1，或与SEQ ID NO.1相比具有插入或缺失时。例如通过将给定RSV F序列与SEQ ID NO.1或本文提供的任何其他RSV F氨基酸序列(即SEQ ID NO.1～91)进行比对，本领域技术人员可以容易地确定，与本文所述的任何特定编号的残基“对应”的氨基酸位置。考虑到RSV F序列在RSV亚型和RSV毒株之间具有高度保守性，无论是利用计算机还是利用眼睛，这种比对都可以很容易地进行。来自不同RSV亚型和毒株的大量WT/天然RSV F分子的氨基酸序列，以及编码这些RSV F分子的核酸序列，是本领域已知的。在SEQ ID NOs:1～20和82～85中提供了几个示例性WT/天然RSV F分子的氨基酸序列。其他此类序列可以在公共序列数据库中找到。在国际专利申请PCT/US2014/048086、美国专利第9,738,689号和美国专利第9,950,058号中描述了其他此类序列，其内容各自通过引用并入本文。
WT/天然RSV-F分子在RSV亚型和RSV毒株之间表现出惊人的高度序列保守性。例如，参见WO2014/160463。例如，RSV亚型A和B对于F0前体分子具有90％的序列一致性。在给定的RSV亚型(例如亚型A或B)中，毒株间的序列一致性约为98％。此外，迄今为止鉴定的几乎所有RSV F F0前体都由574个氨基酸组成。在长度上可能有一些微小的差异——这些差异通常发生在胞质结构域。
本文所述的突变为酪氨酸的特定突变，可引入到任何合适的RSV F“背景”序列中。
在一些实施方式中，这种“背景”序列是WT/天然RSV F分子的序列(即存在于自然界中的RSV F分子序列)。来自不同RSV亚型和毒株的大量WT/天然RSV F分子的氨基酸和核苷酸序列是本领域已知的。几个示例性WT/天然RSV F分子的氨基酸序列提供在SEQ IDNOs:1～20和82～85(参见表1和序列表)中。在国际专利申请号PCT/US2014/048086、美国专利第9,738,689号和美国专利第9,950,058号中描述了其他此类序列，其内容各自通过引用并入本文。
在一些实施方式中，这种“背景”序列是突变RSV F分子的序列——即与WT/天然RSV F分子相比，包含一个或多个人工引入的突变的序列。例如在一些实施方式中，“背景”RSV F序列可包括“Cav1”突变、“DS”突变或其组合。其中可引入本文所述特定突变的合适突变背景RSV分子的非限制性示例，包括具有SEQ ID Nos 86～91中任一氨基酸序列的那些序列，或包含SEQ ID Nos 86～91(参见表1和序列表)中任一个的第26～109位氨基酸(即F2)和第137～513位氨基酸(即F1)的那些序列。其中可引入本文所述特定突变的其他合适突变背景RSV分子，包括国际专利申请PCT/US2014/048086、美国专利第9,738,689号和美国专利第9,950,058号中描述的那些。
在一些实施方式中，“背景”RSV F分子——其中可引入本文所述的特定突变——可以是“全长”RSV F分子，即包括跨膜结构域和胞质结构域。其中可引入本文所述特定突变和交联的合适的“全长”背景RSV分子的非限制性示例，包括具有SEQ ID Nos1～9、11～29、31～49、51～80、83、85、87或89中任一个的氨基酸序列的那些，或包含SEQ ID Nos 1～9、11～29、31～49、51～80、83、85、87或89(参见表1和序列表)中任一个的第26～109位氨基酸(F2)和第137～513位氨基酸(F1)的那些。
在一些实施方式中，“背景”RSV F分子——其中可引入本文所述的特定突变和交联——可以是“可溶性”RSV F分子，即不包括跨膜结构域和胞质结构域。其中可引入本文所述特定突变和交联的合适的“可溶性”背景RSV分子的非限制性示例，包括具有SEQ ID Nos10、30、50、81、82、84、86、88或90中任一个的氨基酸序列的那些，或包含SEQ ID Nos 10、30、50、81、82、84、86、88或90中任一个的第26～109位氨基酸(即F2)和第137～513位氨基酸(即F1)的那些。
类似地，在一些实施方式中，可溶性“背景”RSV F分子——其中可引入本文所述的特定突变和交联——可通过移除“全长”RSV F分子的跨膜结构域和胞质结构域来构建，例如通过去除“全长”RSV F分子的第514位氨基酸以后的序列——例如上述RSV F分子之一。
在一些实施方式中，本发明提供了突变RSV F分子，其包含在第42位氨基酸残基处突变为酪氨酸的点突变(可称为428Y点突变)，或在例如通过与SEQ ID NO.1比对和/或使用SEQ ID NO.1的氨基酸编号确定的、与第428位对应的氨基酸处，突变为酪氨酸的点突变。
在一些实施方式中，包含428Y突变的这些突变RSV F分子还包含，在第185位氨基酸残基处突变为酪氨酸的点突变(可称为185Y点突变)，或在例如通过与SEQ ID NO.1比对和/或使用SEQ ID NO.1的氨基酸编号来确定的、与第185位对应的氨基酸处，突变为酪氨酸的点突变。因此，这些突变体包含428Y突变和185Y突变。
在一些实施方式中，包含428Y突变的这些突变RSV F分子还包含，在第226位氨基酸残基处突变为酪氨酸的点突变(可称为226Y点突变)，或在例如通过与SEQ ID NO.1比对和/或使用SEQ ID NO.1的氨基酸编号来确定的、与第226位对应的氨基酸处，突变为酪氨酸的点突变。因此，这些突变体包含428Y突变和226Y突变。
在一些实施方式中，包含428Y突变的这些突变RSV F分子还包含：(a)在第226位氨基酸残基处突变为酪氨酸的点突变(可称为226Y点突变)，或在例如通过与SEQ ID NO.1比对和/或使用SEQ ID NO.1的氨基酸编号来确定的、与第226位对应的氨基酸处，突变为酪氨酸的点突变；和，(b)在第185位氨基酸残基处突变为酪氨酸的点突变(可称为185Y点突变)，或在例如通过与SEQ ID NO.1比对和/或使用SEQ ID NO.1的氨基酸编号来确定的、与第185位对应的氨基酸处，突变为酪氨酸的点突变。因此，这些突变体包括428Y突变、185Y突变和226Y突变。
在一些实施方式中，突变RSV F分子包含跨膜结构域和胞质结构域。在一些实施方式中，突变RSV F分子不包含跨膜结构域和/或胞质结构域，即，其为可溶性(非膜结合)RSVF分子。
在一些实施方式中，突变RSV F分子是RSV A型或RSV B型分子。
在一些实施方式中，突变RSV F分子能够与预融合特异性抗体结合。在一些实施方式中，突变RSV F分子能够与识别抗原位点
Figure BDA0002444986400000111
的抗体，例如在美国专利第9,738,689号、美国专利第9,950,058号或McLellan等(2013)Science 342:592-598中描述的抗体之一结合，其各自通过引用整体并入本文。此类抗体的非限制性示例包括D25、5C4和AM22。其他识别抗原位点
Figure BDA0002444986400000112
的抗体在本文公开，或在本领域是已知的。
在一些实施方式中，突变RSV F分子包含F2多肽和F1多肽，其中F2多肽的C-末端与F1多肽的N-末端通过二硫键连接。在一些实施方式中，突变RSV F分子包含F2多肽和F1多肽，其中F2多肽的C-末端与F1多肽的N-末端通过人工引入的肽接头连接。
在一些实施方式中，突变RSV F分子包括：(a)F2多肽，其包含约84个氨基酸残基或由约84个氨基酸残基组成；和，(b)F1多肽，其包含约375个氨基酸残基或由约375个氨基酸残基组成。
在一些实施方式中，突变RSV F分子包含：(a)F2多肽，其包含约74～84个氨基酸残基或由约74～84个氨基酸残基组成；和，(b)F1多肽，其包含约365～375个氨基酸残基或由约365～375个氨基酸残基组成。
在一些实施方式中，突变RSV F分子包含：(a)F2多肽，其包含SEQ ID NOs 21～81中任一个的第26～109位氨基酸残基，或由SEQ ID NOs 21～81中任一个的第26～109位氨基酸残基组成；和，(b)F1多肽，其包含SEQ ID NOs 21～81中任一个的第137～513位氨基酸残基，或由SEQ ID NOs 21～81中任一个的第137～513位氨基酸残基组成。
在一些实施方式中，突变RSV F分子包含：(a)F2多肽，其包含SEQ ID NOs 21～81中任一个的第26～109位氨基酸残基中的约74～84个氨基酸，或由SEQ ID NOs 21～81中任一个的第26～109位氨基酸残基中的约74～84个氨基酸组成；和，(b)F1多肽，其包含SEQ IDNOs 21～81中任一个的第137～513位氨基酸残基中的约365～375个氨基酸，或由SEQ IDNOs 21～81中任一个的第137～513位氨基酸残基中的约365～375个氨基酸组成。
在一些实施方式中，突变RSV F分子包含：(a)F2多肽，其包含SEQ ID NO 81的第26～109位氨基酸残基，或由SEQ ID NO 81的第26～109位氨基酸残基组成；和，(b)F1多肽，其包含SEQ ID NO.81的第137～513位氨基酸残基，或由SEQ ID NO.81的第137～513位氨基酸残基组成。
在一些实施方式中，突变RSV F分子包含：(a)F2多肽，其包含SEQ ID NO 81的第26～109位氨基酸残基中的约74～84个氨基酸，或由SEQ ID NO 81的第26～109位氨基酸残基中的约74～84个氨基酸组成；和，(b)F1多肽，其包含SEQ ID NO.81的第137～513位氨基酸残基中的约365～375个氨基酸，或由SEQ ID NO.81的第137～513位氨基酸残基中的约365～375个氨基酸组成。
在一些实施方式中，突变RSV F分子通过一个或多个二酪氨酸交联，稳定处于预融合构象。
在一些实施方式中，突变RSV F分子为成熟RSV F三聚体。在一些这类实施方式中，RSV F分子是通过三个或更多个二酪氨酸交联，稳定处于预融合构象的成熟RSV F三聚体。
在一些实施方式中，突变RSV F分子包含在第428位氨基酸处(或与其对应的氨基酸位置——例如通过与SEQ ID NO.1比对，和/或使用SEQ ID NO.1的氨基酸编号来确定)的酪氨酸，与在第185位氨基酸位置处(或与其对应的氨基酸位置——例如通过与SEQ IDNO.1比对，和/或使用SEQ ID NO.1的氨基酸编号来确定)的酪氨酸之间的二酪氨酸交联。
在一些实施方式中，突变RSV F分子包含在第198位氨基酸处(或与其对应的氨基酸位置——例如通过与SEQ ID NO.1比对，和/或使用SEQ ID NO.1的氨基酸编号来确定)的酪氨酸，与在第226位氨基酸处(或与其对应的氨基酸位置——例如通过与SEQ ID NO.1比对，和/或使用SEQ ID NO.1的氨基酸编号来确定)的酪氨酸之间的二酪氨酸交联。
在一些实施方式中，突变RSV F分子包含以下两者：(a)在第198位氨基酸处(或与其对应的氨基酸位置——例如通过与SEQ ID NO.1比对，和/或使用SEQ ID NO.1的氨基酸编号来确定)的酪氨酸，与在第226位氨基酸处(或与其对应的氨基酸位置——例如通过与SEQ ID NO.1比对，和/或使用SEQ ID NO.1的氨基酸编号来确定)的酪氨酸之间的二酪氨酸交联；和，(b)在第428位氨基酸处(或与其对应的氨基酸位置——例如通过与SEQ ID NO.1比对，和/或使用SEQ ID NO.1的氨基酸编号来确定)的酪氨酸，与在第185位氨基酸处(或与其对应的氨基酸位置——例如通过与SEQ ID NO.1比对，和/或使用SEQ ID NO.1的氨基酸编号来确定)的酪氨酸之间的二酪氨酸交联。
在一些实施方式中，突变RSV F分子为成熟RSV F三聚体，包含三个二酪氨酸交联——其中各二酪氨酸交联均在第428位氨基酸处(或与其对应的氨基酸位置——例如通过与SEQ ID NO.1比对，和/或使用SEQ ID NO.1的氨基酸编号来确定)的酪氨酸，与第185位氨基酸处(或与其对应的氨基酸位置——例如通过与SEQ ID NO.1比对，和/或使用SEQ IDNO.1的氨基酸编号来确定)的酪氨酸之间。
在一些实施方式中，突变RSV F分子为成熟RSV F三聚体，包含三个二酪氨酸交联——其中各二酪氨酸交联均在第198位氨基酸处(或与其对应的氨基酸位置——例如通过与SEQ ID NO.1比对，和/或使用SEQ ID NO.1的氨基酸编号来确定)的酪氨酸，与第226位氨基酸处(或与其对应的氨基酸位置——例如通过与SEQ ID NO.1比对，和/或使用SEQ IDNO.1的氨基酸编号来确定)的酪氨酸之间。
在一些实施方式中，突变RSV F分子为成熟RSV F三聚体，包含六个二酪氨酸交联——其中，三个二酪氨酸交联在第198位氨基酸处(或与其对应的氨基酸位置——例如通过与SEQ ID NO.1比对，和/或使用SEQ ID NO.1的氨基酸编号来确定)的酪氨酸，与第226位氨基酸处(或与其对应的氨基酸位置——例如通过与SEQ ID NO.1比对，和/或使用SEQ IDNO.1的氨基酸编号来确定)的酪氨酸之间；和，三个二酪氨酸交联在第428位氨基酸处(或与其对应的氨基酸位置——例如通过与SEQ ID NO.1比对，和/或使用SEQ ID NO.1的氨基酸编号来确定)的酪氨酸，与第185位氨基酸处(或与其对应的氨基酸位置——例如通过与SEQID NO.1比对，和/或使用SEQ ID NO.1的氨基酸编号来确定)的酪氨酸之间。
在一些实施方式中，突变RSV F分子还包含一个或多个人工引入的非DT交联。在一些此类实施方式中，所述非DT交联为二硫键。在一些此类实施方式中，所述RSV F分子包含一个或多个突变为半胱氨酸的点突变。在一些此类实施方式中，一个或多个二硫键形成在两个半胱氨酸之间——其中一个或两个半胱氨酸通过点突变引入。在一些此类实施方式中，RSV F分子包含在第155位氨基酸残基处突变为半胱氨酸的点突变(即155C突变)。在一些此类实施方式中，RSV F分子包含在第290位氨基酸残基处突变为半胱氨酸的点突变(即290C突变)。在一些此类实施方式中，RSV F分子包括在第155位氨基酸残基处突变为半胱氨酸的点突变(即155C突变)，和在第290位氨基酸残基处突变为半胱氨酸的点突变(即290C突变)。在一些此类实施凡是中，RSV F分子包含在美国专利第9,738,689号、美国专利第9,950,058号或McLellan等(2013)Science342:592-598中公开的，一个或多个突变为半胱氨酸的点突变，其各自通过引用整体并入本文。
在一些实施方式中，突变RSV F分子还包含一个或多个人工引入的空腔填充突变(例如替换)。在一些此类实施方式中，RSV F分子包含在第190位氨基酸残基处突变为F的突变(190F突变)。在一些此类实施方式中，RSV F分子包含在第207位氨基酸残基处突变为L的点突变(207L突变)。在一些此类实施方式中，RSV F分子包含在第190位氨基酸残基处突变为F的突变(190F突变)和在第207位氨基酸残基处突变为L的点突变(207L突变)两者。在一些此类实施方式中，RSV F分子包含一个或多个空腔填充氨基酸替换，选自由58W、83W、87F、90L、153W、190F、203W、207L、220L、260W、296F和298L组成的组。在一些此类实施方式中，RSVF分子包含在美国专利第9,738,689号、美国专利第9,950,058号或McLellan等(2013)Science 342:592-598中公开的一个或多个空腔填充氨基酸替换，其各自通过引用整体并入本文。
在一些实施方式中，突变RSV F分子包含低聚化(oligomerization)结构域，例如三聚化结构域。在一个实施方式中，三聚化结构域为T4折叠子(foldon)结构域、GCN4结构域或T4纤维蛋白(fibrinitin)结构域。其他可使用的三聚化结构域示例包括但不限于在以下文献中描述的三聚化结构域：Habazettl等2009年(Habazettl et al.,2009.NMRStructure of a Monomeric Intermediate on the Evolutionarily OptimizedAssembly Pathway of a Small Trimerization Domain.J.Mol.Biol.pp.null)；Kammerer等2005年(Kammerer et al.,2005.A conserved trimerization motif controls thetopology of short coiled coils.Proc Natl Acad Sci USA 102(39):13891-13896)；Innamorati等2006年(Innamorati et al.,2006.An intracellular role for the C1q-globular domain.Cell signal 18(6):761-770)；Schelling等2007年(Schelling etal.,2007.The reovirusσ-1aspartic acid sandwich:A trimerization motif poisedfor conformational change.Biol Chem 282(15):11582-11589)；Pancera等2005年(Soluble Mimetics of Human Immunodeficiency Virus Type 1Viral Spikes Producedby Replacement of the Native Trimerization Domain with a HeterologousTrimerization Motif:Characterization and Ligand Binding Analysis.J Virol 79(15):9954-9969)；Guthe等2004年(Very fast folding and association of atrimerization domain from bacteriophage T4 fibritin.J.Mol.Biol.v337 pp.905-15)；和Papanikolopoulou等2008年(Creation of hybrid nanorods from sequences ofnatural trimeric fibrous proteins using the fibritin trimerizationmotif.Methods Mol Biol 474:15-33)。
在一些实施方式中，突变RSV F分子包含SEQ ID NO.93的折叠子(foldon)结构域。
在一些实施方式中，突变RSV F分子还包含一个或多个用于检测和/或纯化RSV F分子的标签(例如C-末端标签)。示例性标签包括但不限于Strep标签、Strep II标签、FLAG标签、谷胱甘肽S-转移酶(GST)标签、绿色荧光蛋白(GFP)标签、血凝素A(HA)标签、组氨酸(His)标签、荧光素酶标签、麦芽糖结合蛋白(MBP)标签、c-Myc标签、蛋白A标签、蛋白G标签等。在一些此类实施方式中，所述RSV F分子包含SEQID NO.95的His标签。在一些此类实施方式中，所述RSV F分子包含SEQ ID NO.96的Strep II标签。在一些此类实施方式中，所述标签是可切割的标签——即，如果需要，它们可以被从突变RSV F分子上切割/移除。在一些此类实施方式中，所述标签位于靠近蛋白酶解切割位点(例如，C-末端)的位置——这样可以使用蛋白酶来移除标签。在一些此类实施方式中，所述RSV F分子包含SEQ ID NO.94的凝血酶切割位点。
在一些实施方式中，突变RSV F分子进一步包含一个或多个肽“接头”序列。合适的接头序列包括但不限于G、GG、GGG、GS和SAIG(SEQ ID NO.92的第1～4位氨基酸)接头序列。所述接头可提供在：F2的C-末端和F1的N-末端之间，F1的C-末端和任何人工三聚化结构域的N-末端之间，和/或在任何其他人工引入的序列，例如三聚化结构域、蛋白酶解切割结构域以及用于检测和/或纯化的标签之间。
在一些实施方式中，突变RSV F分子包含一个或多个前导序列、前体多肽序列、分泌信号和/或定位信号。
在本发明的，涉及突变RSV F分子(例如SEQ ID Nos 21～81)或“背景”RSV F分子(例如SEQ ID Nos 1～20或82～91)的特定示例性氨基酸序列的实施方式，或者涉及与这些序列的特定区域(例如其F1和/或F2区域)的实施方式中，也可以使用与这些氨基酸序列等同的变体形式。例如，在一些实施方式中，可以使用，在跨越其F1和F2区域(尤其是跨越第26～109位(F2)和第137～513位(F1的不包括跨膜和胞质结构域的部分)氨基酸残基)，与本文所述任何RSV F氨基酸序列具有至少90％、95％、96％、97％、98％或99％序列一致性的氨基酸序列。在一些实施方式中，可以使用，在跨越这些F1和F2区域，与所述氨基酸序列具有至少约80％或至少85％序列一致性的氨基酸序列。与本文提供的一个或多个特定氨基酸序列相比，这些变体形式可能具有添加、缺失或替换的氨基酸。因此，它们的长度可以长于或短于特定序列。
类似地，可以移除或改变，本文提供的各示例性RSV F氨基酸序列的第514位以后的氨基酸残基。例如，在本文提供的几个氨基酸序列中，第514位以后的氨基酸残基包括天然RSV F跨膜和胞质结构域。在一些实施方式中，这些天然RSV F的跨膜和胞质结构域可被移除，以产生可溶(即非膜结合)型式的RSV F分子，或可被替换成不同的跨膜和/或胞质结构域。类似地，在本文提供的几个氨基酸序列中，第514位以后的氨基酸残基包括各种人工添加的C-末端序列的组合——例如SEQ ID NO.92中提供的人工C-末端序列，其包括折叠子(foldon)结构域(SEQ ID NO.93)、凝血酶切割位点(SEQ ID NO.94)、组氨酸标签(SEQ IDNO.95)、Strep II标签(SEQ ID NO.96)和各种接头。在一些实施方式中，根据需要，可移除、修饰、重排或替换这些人工C-末端序列。例如，在一些实施方式中，可以使用不同的三聚化结构域，和/或可以使用不同的切割位点，和/或可以使用不同的表位标签。
在一些实施方式中，本文所述的一个或特定突变RSV F分子内的一个或多个氨基酸残基可被另一个氨基酸替换。在一些实施方式中，一个或多个氨基酸残基可被另一个具有相似极性且可作为功能等同物的氨基酸替换，造成沉默改变。在一些实施方式中，序列内的氨基酸的取代可选自该氨基酸所属类别的其它成员，例如以创建保守替换。例如，非极性(疏水性)氨基酸包括丙氨酸、亮氨酸、异亮氨酸、缬氨酸、脯氨酸、苯丙氨酸、色氨酸和甲硫氨酸。极性中性氨基酸包括甘氨酸、丝氨酸、苏氨酸、半胱氨酸、酪氨酸、天冬酰胺和谷氨酰胺。带正电荷的(碱性)氨基酸包括精氨酸、赖氨酸和组氨酸。带负电荷的(酸性)氨基酸包括天冬氨酸和谷氨酸。这种替换通常理解为保守替换。
在一些实施方式中，人工、合成或非典型氨基酸或化学氨基酸类似物，可用于制造本文所述的突变RSV F分子。非典型氨基酸包括，但不限于，普通氨基酸的D-异构体、含氟氨基酸和“设计”氨基酸，例如β-甲基氨基酸、Cγ-甲基氨基酸、Nγ-甲基氨基酸和一般氨基酸类似物。非典型氨基酸的额外的非限制性示例包括，但不限于：α-氨基辛酸，Acpa；(S)-2-氨基乙基-L-半胱氨酸/HCl，Aecys；氨基苯乙酸，Afa；6-氨基己酸，Ahx；γ-氨基异丁酸和α-氨基异丁酸，Aiba；别异亮氨酸，Aile；L-烯丙基甘氨酸，Alg；2-氨基丁酸、4-氨基丁酸和α-氨基丁酸，Aba；p-氨基苯丙氨酸，Aphe；b-丙氨酸，Bal；p-溴苯丙氨酸，Brphe；环己胺，Cha；瓜氨酸，Cit；β-氯丙氨酸，Clala；环亮氨酸，Cle；p-胆碱苯丙氨酸，Clphe；半胱磺酸，Cya；2,4-二氨基丁酸，Dab；3-氨基丙酸和2,3-二氨基丙酸，Dap；3,4-脱氢丙氨酸，Dhp；3,4-二羟基苯丙氨酸，Dhphe；p-氟苯基丙氨酸，Fphe；D-氨基葡萄糖酸，Gaa；高精氨酸，Hag；δ-羟基赖氨酸/HCl，Hlys；DL-β-羟基正缬氨酸，Hnvl；高谷氨酰胺，Hog；高苯丙氨酸，Hoph；高丝氨酸，Hos；羟脯氨酸，Hpr；p-碘苯丙氨酸，Iphe；异丝氨酸，Ise；α-甲基亮氨酸，Mle；DL-甲硫氨酸-S-甲基硫酰氯，Msmet；3-(1-萘基)丙氨酸，1Nala；3-(2-萘基)丙氨酸，2Nala；去亮氨酸，Nle；N-甲基丙氨酸，Nmala；正缬氨酸，Nva；O-苄基丝氨酸，Obser；O-苄基酪氨酸，Obtyr；O-乙基酪氨酸，Oetyr；O-甲基丝氨酸，Omser；O-甲基酪氨酸，Omtyr；鸟氨酸，Orn；苯甘氨酸；青霉胺，Pen；焦谷氨酸，Pga；哌啶酸，Pip；肌氨酸，Sar；叔丁基甘氨酸；叔丁基拉兰酸；3,3,3-三氟丙氨酸，Tfa；6-羟基多巴，Thphe；L-乙烯基甘氨酸，Vig；(-)-(2R)-2-氨基-3-(2-氨基乙基磺酰基)丙酸二氢氯，Aaspa；(2S)-2-氨基-9-羟基-4,7-二氧杂壬酸，Ahdna；(2S)-2-氨基-6-羟基-4-氧己酸，Ahoha；(-)-(2R)-2-氨基-3-(2-羟乙基磺酰基)丙酸，Ahsopa；(-)-(2R)-2-氨基-3-(2-羟乙基亚砜)丙酸，Ahspa；(2S)-2-氨基-12-羟基-4,7,10-三氧十二酸，Ahtda；(2S)-2,9-二氨基-4,7-二氧杂壬酸，Dadna；(2S)-2,12二氨基-4,7,10-三氧十二酸，Datda；(S)-5,5-二氟去亮氨酸，Dfnl；(S)-4,4-二氟正缬氨酸，Dfnv；(3R)-1-1-二氧代-[1,4]噻嗪-3-羧酸，Dtca；(S)-4,4,5,5,6,6,6,6-七氟去亮氨酸，Hfnl；(S)-5,5,6,6,6-五氟去亮氨酸，Pfnl；(S)-4,5,5,5-五氟正缬氨酸，Pfnv；和(3R)-1,4-噻嗪-3-羧酸。此外，氨基酸可以是D(右旋的)或L(左旋的)。关于典型氨基酸和非典型氨基酸的综述，请参见Sandberg等人1998(Sandberg et al.,1998.New chemical descriptors relevant for thedesign of biologically active peptides.A multivariate characterization of87amino acids.J Med Chem 41(14):pp.2481-91)。
突变RSV-F分子的特性
本发明的突变RSV F分子——包括，含本文提供的示例性氨基酸序列(例如SEQ IDNos.21～81)之一的氨基酸序列的那些，含这些示例性氨基酸序列之一的第26～109位和/或第137～513位残基的那些，含这些示例性氨基酸序列之一的F1和/或F2多肽的那些，以及这些特定氨基酸序列的变体形式——应：(a)包含F1多肽和F2多肽，(b)能够形成或经加工(如从前体例如F0)形成，能够采取预融合构象(如本文描述/定义)的成熟RSV F三聚体。在一些实施方式中，本发明的突变RSV F分子还可以具有以下一种或多种特性：(1)与pre-F特异性抗体结合，(2)与结合位点
Figure BDA0002444986400000151
的抗体结合，(3)与中和抗体结合，(4)与广泛中和抗体结合，(5)与选自由D25、AM22、5C4、101F组成的组中的抗体结合，(6)与帕利珠单抗(Synagis)结合，(7)结合到和/或激活B细胞受体，(8)在动物体内引起抗RSV的抗体反应，(9)在动物体内引起保护性抗RSV的抗体反应，(10)在动物体内诱发产生抗RSV的中和抗体，(11)在动物体内诱发产生抗RSV的广泛中和抗体，(12)在动物体内诱发产生识别四阶中和表位(QNE)的抗RSV抗体，和/或(13)在动物体内诱发抗RSV的保护性免疫应答。
DT交联
在一些实施方式中，本发明提供了包含至少一个人工引入的DT交联的突变RSV F分子。所述DT交联有助于将本文所述的突变RSV F分子稳定在其预融合构象。
在一些实施方式中，所述DT交联可引入在两个内源性酪氨酸残基之间，两个人工引入的酪氨酸残基之间(即源自“突变为酪氨酸”的突变)，或人工引入的酪氨酸残基与内源性酪氨酸残基之间。
在一些实施方式中，至少一个DT交联的至少一个酪氨酸源自突变为酪氨酸的点突变(即，通过突变为酪氨酸的点突变引入)。在一些实施方式中，本发明提供了包含至少三个DT交联的突变三聚体RSV F分子，其中至少三个DT交联中的每一个的至少一个酪氨酸源自突变为酪氨酸的点突变(即，通过突变为酪氨酸的点突变引入)。
例如，在一些实施方式中，本发明提供了突变RSV F分子，其包含在第198位残基处的酪氨酸(通常为天然存在的酪氨酸)和第226位残基处引入的酪氨酸(即由226Y突变造成)之间的DT交联——即，分子内198Y-226Y DT交联。在突变RSV F分子为三聚体的实施方式中，三聚体因此包含三个分子内198Y-226Y DT交联。
在一些实施方式中，本发明提供了突变RSV F分子，其包含在第185位残基处引入的酪氨酸(即由185Y突变造成)和第428位残基处引入的酪氨酸(即由428Y突变造成)之间的DT交联——即，分子间185Y-428Y DT交联。在突变RSV F分子为三聚体的实施方式中，三聚体因此包含三个分子间185Y-428Y DT交联。
在一些实施方式中，本发明提供了包含198Y-226Y分子内DT交联和185Y-428Y分子间DT交联两者的突变RSV F分子。在突变RSV F分子为三聚体的实施方式中，三聚体因此包含六个DT交联——三个分子内198Y-226Y DT交联和三个分子间185Y-428Y DT交联。
如上所述，成熟RSV F三聚体的每个原聚体均包含两种不同的多肽——称为F1和F2——它们以非共价方式结合形成原聚体。在同一原聚体内，F1多肽和F2多肽之间的键就是分子间键和原聚体内键的实例。185Y-428Y DT交联经设计，用于将三聚体的两个原聚体保持在一起——即它是分子间、原聚体间的键。一个原聚体上的第185位的酪氨酸与另一个原聚体上第428位的酪氨酸形成二酪氨酸键。
本专利公开的实施例部分，提供了进行DT交联反应的示例性方法。此外，进行DT交联的方法是本领域已知的，并且在例如Marshall等人、美国专利第7,037,894号和第7,445,912号中有描述——其内容通过引用并入本文。二酪氨酸交联引入了变化最小，且长度为零的共价碳碳键。DT交联在生理条件下不会被水解。二酪氨酸交联已知是安全的，因为它们可在体内自然形成，而且它们大量存在于普通食品中。例如，DT键形成了小麦蛋白粉的结构。二酪氨酸键在体外不会自发形成。而是必须进行酶促交联反应，其中含有酪氨酰基侧链的蛋白质经受导致DT键形成的反应条件。这些条件是，或成为，氧化反应条件，因为DT键形成反应是氧化交联反应。在一些实施方式中，DT交联反应条件产生，未经修饰或没有可检测到的修饰的蛋白质。这些条件可以通过使用催化H2O2形成的酶来得到，例如过氧化物酶。DT键的形成，可利用激发波长约为320nm的分光光度法进行监测，并在波长约为400nm处测量荧光(参见，例如，图34)，并可通过标准程序监测酪氨酰基荧光的损失。当酪氨酰基荧光的损失与DT键的形成不再成化学计量比时，可通过本领域技术人员已知的任何方法来停止反应，例如，通过添加还原剂，并随后(在冰上)冷却或冷冻样品来停止反应。美国专利第7,037,894号和第7,445,912号以及本专利公开的实施例部分，描述了合适的DT交联方法的其他细节。
核酸分子
在一些实施方式中，本发明提供了编码本文所述突变RSV F分子的核酸分子，以及包含所述核酸分子的载体。本领域普通技术人员可以容易地确定，编码本文所述的任意突变RSV F分子的核酸分子的核酸序列——鉴于本领域普通技术人员中对遗传密码的普遍已知和理解的性质。
在一些实施方式中，核酸分子编码前体F0多肽，该前体F0多肽在适当的细胞中表达时，将被正确地加工以生成成熟RSV F分子。例如，在一些实施方式中，核酸分子可编码前体(F0)多肽之一，其氨基酸序列提供在表1和序列表中。在一些实施方式中，核酸分子仅可编码F2多肽或仅可编码Fl多肽。
可使用本领域已知的任何适当的方法，来获得或制备编码本文所述突变RSV F分子的核酸分子。例如，编码突变RSV F分子的核酸分子，可以从克隆的DNA中获得，或通过化学合成制备。在一些实施方式中，核酸分子可通过反向转录RNA来获得，其中RNA通过本领域普通技术人员已知的任何方法来制备。点突变，或本文所述的任何其他修饰(例如，去除C-末端序列、替换C-末端序列等)，可通过本领域普通技术人员熟知和理解的DNA标准重组方法来完成。例如，本领域普通技术人员通过对编码要突变为酪氨酸的特定氨基酸残基的核苷酸密码子进行定位(例如，编码第185、226或428位氨基酸残基的核苷酸密码子)，如需要，可将该密码子的核苷酸进行突变，以产生编码酪氨酸的密码子，可以容易地进行如本文所述的“突变为酪氨酸”突变。
无论来源如何，编码本发明突变RSV F分子的核酸分子，可以被克隆到任何合适的载体中，例如用于核酸分子增殖的载体或用于核酸分子表达的载体。在需要表达的实施方式中，核酸可操作性地连接至适于在所需细胞类型，例如哺乳动物细胞或昆虫细胞中进行定向表达的启动子，并且可并入任何合适的表达载体，例如哺乳动物或昆虫表达载体中。
在一些实施方式中，编码本发明突变RSV F分子的核酸分子，可以针对在特定生物体或物种的细胞中表达而进行密码子优化。例如，国际专利申请PCT/US2014/048086提供了针对在人、仓鼠、小鼠和昆虫细胞中表达，而进行密码子优化的RSV F分子的核苷酸序列。这种编码RSV F蛋白的经密码子优化的核苷酸序列，可以用作引入本文所述的任何特定突变的“背景”序列。
制造方法
本发明的突变RSV F分子可以通过本领域已知的任何合适方法制备得到。通常，利用用于生产重组蛋白的标准方法，来制备突变RSV-F分子。例如，编码本发明突变RSV F分子的核酸分子可以在任何合适的细胞类型中表达，包括但不限于哺乳动物细胞和昆虫细胞(例如SF9或Hi5细胞，例如利用杆状病毒表达系统)。由核酸分子表达蛋白质的方法，在本领域是常规且熟知的，并且可以使用本领域已知的任何合适的方法、载体、系统和细胞类型。例如，通常将编码本发明突变RSV F分子的核酸分子放置到包含合适启动子的合适表达构建体中，然后将其传递至细胞进行表达。
在一些实施方式中，本发明的突变RSV F分子是稳定处于pre-F构象的成熟RSV F三聚体。在这些实施方式中，通常编码突变RSV F分子的核酸分子在细胞中表达成可溶形式，然后允许组装成正常的三聚体pre-F构象，之后分子进行酶促DT交联反应。在一些实施方式中，在酶促交联反应之前和/或期间，例如在进行交联时，可获得处于(和/或保持在)pre-F构象的突变RSV F分子。在一些实施方式中，突变RSV F分子可以以这样的方式产生和/或分离，该方式使得大多数或基本上全部的突变RSV F分子以pre-F构象存在。在一些实施方式中，可从RSV F蛋白分子的混合群体中分离处于pre-F构象的突变RSV F分子，该混合群体包含一些处于pre-F构象的RSV F分子和一些处于其他构象的RSV F分子。在一些实施方式中，RSV F蛋白在细胞中表达(例如以其膜结合或可溶形式)，并自发组装成其正常的pre-F构象。在一些实施方式中，在DT交联之前，不需要额外的稳定化将突变RSV F分子保持在其pre-F形式。在一些实施方式中，可将突变RSV F分子保持在有利于形成和/或保持pre-F构象的特定条件下或特定组合物中。例如，在一些实施方式中，处于其pre-F构象的突变RSVF分子中可以在没有细胞的情况下保持——与细胞接触可能会触发其转换为post-F构象。突变RSVF分子可以使用本领域已知的任何合适方法来获得和/或分离和/或保持在pre-F构象，包括但不限于标准蛋白质纯化方法，例如离子交换色谱法、尺寸排除色谱法和/或亲和色谱法。在一些实施方式中，突变RSV F分子可在一些分子的存在下表达，或在与这些分子共表达或接触下表达，这些分子与RSV F蛋白结合并使其稳定处于pre-F构象，包括但不限于抗体、小分子、肽和/或拟肽。结合预融合RSV F蛋白的非限制性示例抗体，包括5C4、AM22和D25抗体(参见McLellan et al.(2013)Science 342:592-598，其通过引用整体并入本文)。在一些实施方式中，可以通过控制蛋白存在于其中的介质/缓冲液的离子强度(例如通过使用高或低离子强度的介质)，来获得、分离或保持处于pre-F构象的突变RSV F分子。在一些实施方式中，可在有利于保存pre-F构象的一个或多个温度下，获得、分离或保持突变RSV F分子。在一些实施方式中，可在一段减少pre-F构象丢失的程度的时间段内，获得、分离或保持突变RSV F分子。
在一些实施方式中，可进行分析，以确认所需构象例如pre-F构象，已在突变RSV F分子中形成和/或保持。这种分析可以在交联之前、交联过程中、交联过程之后，或在这些阶段的任何组合中进行。这种分析可包括本领域已知的，用于评估蛋白质或蛋白质复合物的三维结构的任何合适方法，包括功能分析、晶体分析等。在一些实施方式中，这种分析可包括评估突变RSV F分子与某些抗体的结合，例如如本文其他地方所述的对pre-F构象的特异性抗体和/或已知与
Figure BDA0002444986400000181
位点结合的抗体，包括但不限于5C4、AM22和D25抗体。
在一些实施方式中，本发明的突变RSV F分子可在制备过程中的一个或多个步骤之前、期间或之后进行纯化。例如，在一些实施方式中，突变RSV F分子可在完成所有制备步骤后纯化。在一些实施方式中，突变RSV F分子可在开始交联处理之前，或在该处理过程中的一个或多个中间方法步骤之后纯化，例如：在突变RSV F分子表达之后，在将突变RSV F分子组装成成熟三聚体之后，在获得处于其pre-F构象的突变RSV F分子之后，或在进行DT交联反应期间或之后。本发明的突变RSV F分子可以使用本领域已知的任何合适方法进行分离或纯化。这些方法包括，但不限于，色谱法(如离子交换、亲和和/或尺寸柱色谱法)、硫酸铵沉淀、离心、差异性溶解，或本领域普通技术人员已知的用于纯化蛋白质的任何其他技术。在具体实施方式中，可能有必要将经DT交联的成熟三聚体突变RSV F分子，与那些未经充分交联的，或那些未充分稳定处于pre-F构象的RSV F分子分离开。这可以使用本领域已知的任何合适的系统来完成。例如，可以使用基于抗体的分离方法，使用pre-F或post-F特异性抗体，将处于pre-F构象的突变RSV-F分子与不处于pre-F构象的突变RSV-F分子分离开。可从用于制备它们的任何来源中，纯化本发明的突变RSV F分子。纯化的程度可能不同，但在各实施方式中，本发明的经纯化的突变RSV F分子以一形式提供，其中它们在最终组成中包含总蛋白的约10％、20％、50％、70％、75％、80％、85％、90％、95％、98％、99％或99.9％。在一些实施方式中，本发明的突变RSV F分子可以通过标准方法，从其他蛋白质或任何其他不需要的产物(例如非交联或非pre-F RSV F)中分离和纯化，所述标准方法包括但不限于色谱法、甘油梯度法、亲和色谱法、离心法、离子交换色谱法、尺寸排除色谱法和亲和色谱法，或通过本领域已知用于纯化蛋白质的任何其他标准技术。要分离的突变RSV F分子可以在高或低离子型介质中表达，或分离在高或低离子型缓冲液或溶液中。本发明的突变RSV F分子也可以在有利于保持所需构象的一个或多个温度下分离。它们也可在减少制剂损失所需构象程度的时间段内分离。蛋白质制剂保持一种或多种所需构象(例如pre-F构象)的程度，可通过本领域已知的任何合适方法来测定，包括但不限于生物化学、生物物理学、免疫学和病毒学分析。这些测定法包括，但不限于，例如免疫沉淀、酶联免疫吸附试验(ELISA)或酶联免疫吸附斑点(ELISPOT)试验、晶体学分析(包括与抗体共结晶)、沉降、分析超速离心、动态光散射(DLS)、电子显微镜(EM)、冷冻电镜断层扫描、量热法、表面等离子体共振(SPR)、荧光共振能量转移(FRET)、圆二色性分析、小角x射线散射、中和试验、抗体依赖性细胞毒性试验和/或体内攻毒研究。
本发明的突变RSV F分子的产率可以通过本领域已知的任何手段来确定，例如，通过将经工程改造的最终蛋白(例如经交联的pre-F RSV)的量与起始物质的量进行比较，或与生产方法的任何前一步骤中存在的物质的量进行比较。蛋白质浓度可通过标准程序测定，例如，布拉德福(Bradford)或劳力(Lowrie)蛋白测定法。Bradford测定法与还原剂和变性剂具有相容性(Bradford,M,1976.Anal.Biochem.72:248)。劳里(Lowry)测定法与洗涤剂具有更好的相容性，且反应与蛋白质浓度和读数更具线性关系(Lowry,O J,1951.Biol.Chem.193:265)。
对特性的测试
在一些实施方式中，可分析本发明的突变RSV F分子或其制备过程中的任何中间体，以确认它们具有所需的特性，例如上文所列或本专利说明书其他地方所标识的一种或多种特性。例如，在一些实施方式中，可进行体外或体内测试，以评估RSV F蛋白的构象结构，稳定性(例如热稳定性)，半衰期(例如在受试者体内)，在溶液中的聚合作用，与抗体(例如中和抗体、泛中和抗体；pre-F特异性抗体；识别位点
Figure BDA0002444986400000191
的抗体、构象特异性抗体、识别亚稳态表位的抗体、D25、AM22、5C4、101F或帕利珠单抗)的结合，与B细胞受体的结合，B细胞受体的激活，抗原性，免疫原性，引发抗体应答的能力，引发保护性抗体/免疫应答的能力，引发产生中和抗体的能力，或引发产生泛中和抗体的能力。在对本发明的突变RSV F分子进行动物体内测试的实施方式中，动物可以是任何合适的动物物种，包括但不限于哺乳动物(例如啮齿动物物种(如小鼠或大鼠)、兔子、雪貂、猪种、牛种、马种、绵羊种，或灵长类动物物种(如人类或非人类灵长类动物)，或禽类物种(例如鸡)。
用于评估蛋白质构象结构的测试法为本领域所熟知，并且可以使用任何合适的测试法，包括但不限于，晶体学分析(例如X射线晶体学或电子晶体学)、沉降试验、分析超速离心、电子显微镜(EM)，冷冻电子显微镜(cryo-EM)、冷冻电镜断层扫描、核磁共振(NMR)、小角度x射线散射、荧光共振能量转移(FRET)试验等。
用于评估蛋白质稳定性的测试法为本领域所熟知，并且可以使用任何合适的测试法，包括但不限于，变性和非变性电泳、等温滴定量热法和时程实验，在时程实验中，在不同的蛋白质浓度、温度、pH值或氧化还原条件下，蛋白质随时间进行孵育和分析。还可以分析蛋白质对蛋白水解降解的敏感性。
用于评估蛋白质与抗体结合的测试法为本领域所熟知，并且可以使用任何合适的测试法，包括但不限于，免疫沉淀试验、酶联免疫吸附试验(ELISA)、酶联免疫吸附斑点试验(ELISPOT)、晶体学分析(包括与抗体共结晶)、表面等离子共振(SPR)测试法、荧光共振能量转移(FRET)测试法等。
用于评估中和活性的测试法为本领域所熟知，并且可以使用任何合适的试验法。例如，可以进行测试，以确定用本发明的RSV F多肽、蛋白质和/或蛋白质复合物对动物进行疫苗接种/免疫，而产生的抗体或抗血清的中和活性。本领域已知的中和试验包括但不限于由Dey等2007年(Dey et al.,2007,Characterization of Human ImmunodeficiencyVirus Type 1Monomeric and Trimeric gp120 Glycoproteins Stabilized in the CD4-Bound State:Antigenicity,Biophysics,and Immunogenicity.J Virol 81(11):5579-5593)和Beddows等2006年(Beddows et al.,2007,A comparative immunogenicity studyin rabbits of disulfide-stabilized proteolytically cleaved,soluble trimerichuman immunodeficiency virus type 1gp140,trimeric cleavage-defective gp140and momomeric gp120.Virol 360:329-340)中描述的那些。
用于评估疫苗免疫原是否能够引发免疫应答，和/或证明保护性免疫的测试法为本领域所熟知，并且可以使用任何合适的测试法。例如，可以进行测试，以确定用本发明的RSV F多肽、蛋白质和/或蛋白质复合物对动物进行疫苗接种/免疫，是否提供抗RSV感染的免疫应答和/或保护性免疫。在一些实施方式中，可在安慰剂组和试验疫苗接种组之间，就其感染率、血清转化率或病毒载量进行比较。
用于评估蛋白质的药物代谢动力学和生物分布的测试法也为本领域所熟知，并且可以使用任何合适的测试法来评估本发明的RSV F多肽、蛋白质和/或蛋白质复合物的这些特性。
组合物
在一些实施方式中，本发明提供了包含本文所述的一种或多种突变RSV F分子的组合物。在一些实施方式中，该组合物可以是药物组合物——即包含适于对活体受试者施用的组分。
在一些实施方式中，本发明的突变RSV F分子可以在组合物中提供，所述组合物包含一种或多种额外的活性成分，例如一种或多种额外的疫苗免疫原或治疗剂。在一些实施方式中，本发明的突变RSV F分子可以在组合物，例如药物组合物中提供，其包含一种或多种其他组分，包括但不限于药物上可接受的载体、佐剂、免疫刺激剂、润湿剂或乳化剂、pH缓冲剂、防腐剂，和/或任何其他适于组合物预期用途的组分。这些组分可以采用溶液、悬浮液、乳液等形式。术语“药物上可接受的载剂”包括本发明的突变RSV F分子可提供在其中或与其一起提供的各种稀释剂、赋形剂和/或媒介物，并且包括但不限于，已知用于安全地向人类和/或其他动物受试者递送的载剂，和/或由联邦或州政府的监管机构批准的载剂，和/或在美国药典和/或其他公认药典中列出的载剂，和/或从一家或多家公认的监管机构获得特别或个别批准用于人类和/或其他动物的载剂。这些药物上可接受的载剂包括，但不限于，水、水性溶液(例如生理盐水溶液、缓冲液等)、有机溶剂(例如某些醇和油，包括石油、动物、植物或合成来源的醇和油，例如花生油、大豆油、矿物油、芝麻油)等。在一些实施方式中，本发明的组合物还包括一种或多种佐剂。示例性佐剂包括，但不限于，明矾佐剂、无机或有机佐剂、油基佐剂、病毒体(virosome)、脂质体、脂多糖(LPS)、抗原分子笼(例如免疫刺激复合物(“ISCOMS”))、Ag修饰的皂甙/胆固醇胶束，其形成稳定的笼状结构，转运到引流淋巴结)、细菌细胞壁成分、内吞核酸(例如双链RNA(dsRNA)、单链DNA(ssDNA)和含DNA的未甲基化CpG二核苷酸)、AUM、磷酸铝，氢氧化铝和鲨烯。在一些实施方式中，用病毒体作佐剂。根据本发明可使用的其他市售佐剂包括，但不限于，Ribi佐剂系统(RAS，含有解毒内毒素(MPL)的水包油乳液和2％鲨烯(Sigma M6536)中的分枝杆菌细胞壁成分)、TiterMax(稳定的，可代谢油包水佐剂(CytRx Corporation150Technology Parkway Technology Park/AtlantaNorcross,Georgia 30092))、Syntex佐剂制剂(SAF，由吐温80和普朗尼克聚氧乙烯/聚氧丙烯嵌段共聚物L121稳定化的水包油乳液(Chiron Corporation,Emeryville,CA))、弗氏完全佐剂、弗氏不完全佐剂、ALUM——氢氧化铝，Al(OH)3(可购于Alhydrogel,AccurateChemical&Scientific Co,Westbury,NY)、超级载体(Syntex Research 3401HillviewAve.P.O.Box 10850Palo Alto,CA 94303)、Elvax 40W1,2(乙烯-乙酸乙烯酯共聚物(DuPont Chemical Co.Wilmington,DE))、与抗原共沉淀的L-酪氨酸(可购于许多化学公司)；Montanide(一种油酸马尼德酯，ISA Seppic Fairfield,NJ))、AdjuPrime(一种碳水化合物聚合物)、硝化纤维素吸附蛋白、Gerbu佐剂(C-C Biotech,Poway,CA)等。
在一些实施方式中，本发明的突变RSV F分子可提供在含糖的组合物中。在一些实施方式中，本发明的RSV F多肽、蛋白质和/或蛋白质复合物可提供在含蔗糖的组合物中。在一些实施方式中，本发明的RSV F多肽、蛋白质和/或蛋白质复合物可提供在含有约5％蔗糖的组合物中。在一些实施方式中，本发明的RSV F多肽、蛋白质和/或蛋白质复合物可提供在含有约10％蔗糖的组合物中。在一些实施方式中，本发明的RSV F多肽、蛋白质和/或蛋白质复合物可提供在含有约15％蔗糖的组合物中。在一些实施方式中，本发明的RSV F多肽、蛋白质和/或蛋白质复合物可提供在含有约20％蔗糖的组合物中。在一些实施方式中，本发明的RSV F多肽、蛋白质和/或蛋白质复合物可提供在含有约25％蔗糖的组合物中。重要的是，人们已经发现，含有蔗糖可减少在本发明的RSV F多肽、蛋白质和/或蛋白质复合物的组合物中的聚集体的形成。
在一些实施方式中，本发明提供了包含“有效量”的本发明突变RSV F分子的组合物。类似地，在一些实施方式中，本发明提供了涉及向受试者，施用“有效量”的突变RSV F分子或包含突变RSV F的组合物的方法。“有效量”是实现预期的最终结果所需的量。预期的最终结果的示例包括，但不限于：产生抗RSV的体液免疫应答，产生抗RSV的中和抗体应答，产生抗RSV的泛中和抗体应答，产生抗RSV的保护性免疫，抑制或RSV病毒复制，以及一种或多种RSV感染症状的改善。有效实现预期的最终结果的本发明突变RSV F分子或包含该分子的组合物的量，可取决于多种因素，包括，但不限于，RSV病毒的类型、亚型和株、受试者的物种(例如，人类或某些其他动物物种)、受试者的年龄、受试者的性别、受试者的体重、计划的给药途径、计划的给药方案、任何持续性RSV感染的严重程度(例如，在治疗应用的情况下)等等。有效量——可能是一系列有效量——可以在无需任何过度实验的情况下，通过标准技术，例如在预期的受试物种或任何合适的动物模型物种中，使用体外测试和/或体内测试来确定。合适的测试法包括，但不限于，那些涉及从剂量-反应曲线，和/或从体外和/或体内模型系统获得的其他数据外推的那些。在一些实施方式中，有效量可根据医生或兽医基于对具体情况的判断来确定。
突变RSV-F分子的应用
在一些实施方式中，本发明的突变RSV F分子可用作研究工具，诊断工具，治疗剂，用于生产抗体试剂或治疗性抗体的靶点，和/或疫苗或疫苗组合物的组分。例如，在一些实施方式中，本发明的突变RSV F分子可用作动物受试者(例如哺乳动物受试者，包括人类)的疫苗免疫原。下面对本发明突变RSV F分子的这些和其他用途作更全面的描述。本领域技术人员应理解，本发明的突变RSV F分子也可用于各种其他应用，并且所有这些应用和用途都旨在落入本发明的范围内。
研究RSV-F抗体的工具
在一个实施方式中，本发明的突变RSV F分子可例如在ELISA试验、Biacore/SPR结合试验和/或本领域已知的任何其他抗体结合试验中，用作测试和/或测量抗RSV F抗体的结合和/或滴度的分析物。例如，本发明的突变RSV F分子可用于分析和/或比较抗RSV F抗体的效果。
产生抗体的工具
本发明的突变RSV F分子也可用于产生治疗性抗体，和/或可用作研究工具的抗体，或用于任何其他所需的用途。例如，本发明的突变RSV F分子可用于免疫，以获得用作研究工具和/或治疗剂的RSV F蛋白抗体。在一些实施方式中，为了产生抗体，本发明的突变RSV F分子可用于免疫非人类动物，例如脊椎动物，包括但不限于小鼠、大鼠、豚鼠、兔、山羊、非人类灵长类动物等。然后可以从动物获得此类抗体，其可以是单克隆抗体或多克隆抗体，和/或产生此类抗体的细胞。例如，在一些实施方式中，本发明的突变RSV F分子可用于免疫小鼠，以产生和获得单克隆抗体，和/或产生这种单克隆抗体的杂交瘤。这些方法可以采用本领域已知的用于产生小鼠单克隆抗体的标准方法来实施，包括用于产生杂交瘤的标准方法。在一些实施方式中，本发明的突变RSV F分子可用于产生嵌合型(如部分人源)、人源化或全人源抗体，例如使用本领域目前已知用于产生嵌合型、人源化和全人源抗体的任何方法，包括但不限于CDR接枝方法、噬菌体展示方法、转基因小鼠方法(如使用经过基因改造以能够产生全人源抗体的小鼠，例如转基因鼠)，和/或本领域已知的任何其他合适的方法。可使用一种或一组的多种抗原(优选包括本发明突变RSV F分子本身)，对使用这种系统制备的针对本发明突变RSV F分子的抗体进行抗原性表征。可通过本领域普通技术人员已知的任何标准方法，对这种抗体进行额外表征，该标准方法包括，但不限于，基于ELISA的方法、基于SPR的方法、生物化学方法(例如但不限于等电点测定)，和本领域已知用于研究抗体的生物分布、安全性和有效性(例如在临床前和临床研究中)的方法。
向受试者施药
在一些实施方式中，本发明提供了包括向受试者施用本发明突变RSV F分子或包含该突变RSV F分子的组合物的方法。这些方法可包括治疗患有RSV的个体的方法(即治疗方法)和/或保护个体免受未来被RSV感染的方法(即预防方法)。
可(例如在治疗方法或免疫接种方法的过程中)施用本发明的突变RSV F分子，或包含该RSV F多肽、蛋白质和/或蛋白质复合物的组合物的受试者，包括任何和所有动物物种，尤其包括，那些易受RSV感染或能为RSV感染研究提供模型动物系统的动物物种。在一些实施方式中，受试者是哺乳动物物种。在一些实施方式中，受试者是禽类物种。哺乳动物受试者包括，但不限于，人类、非人灵长类动物、啮齿动物、兔和雪貂。禽类受试者包括，但不限于鸡，例如家禽养殖场的鸡。在一些实施方式中，施用本发明突变RSV F分子或包含该突变RSV F分子的组合物的受试者要么患有RSV，要么具有RSV感染的风险。在一些实施方式中，受试者的免疫功能衰退。在一些实施方式中，受试者患有心脏疾病或失调。在一些实施方式中，受试者的年龄大于约50岁，或大于约55岁，或大于约60岁，或大于约65岁，或大于约70岁，或大于约75岁，或大于约80岁，或者大于约85岁，或者大于约90岁。在一些实施方式中，受试者的年龄小于约1个月，或小于约2个月，或小于约3个月，或小于约4个月，或小于约5个月，或小于约6个月，或小于约7个月，或小于约8个月，或小于约9个月，或者小于约10个月，或小于约11个月，或小于约12个月，小于约13个月，或小于约14个月，或小于约15个月，或小于约16个月，或小于约17个月，或小于约18个月，或小于约19个月，或小于约20个月，或小于约21个月，或小于约22个月，或小于约23个月。
本领域已知各种递送系统，并且任何合适的递送系统都可用于将本发明的组合物施用于受试者。这种递送系统包括，但不限于，皮内、肌肉内、腹腔内、静脉内、皮下、鼻内、硬膜外和口服递送系统。本发明的组合物可以通过任何方便的途径施用，例如通过输液或团注，通过上皮或粘膜皮肤衬里(例如口腔粘膜、直肠和肠粘膜等)吸收，并且可以与其他生物活性剂一起施用。施药可以是全身的，或可以是局部的。也可以使用肺部施药，例如，通过使用吸入器或雾化器，以及使用含雾化剂的制剂。
在一些实施方式中，可能需要将本发明的药物组合物局部施用于，突变RSV F分子在其中可最有效产生所需结果的组织。这可以通过，例如，局部输液、注射、使用导管递送，或通过植入物，例如多孔、非多孔或凝胶状的植入物，或包含一种或多种膜(例如硅胶膜)或纤维的植入物，蛋白质或蛋白质复合物可以从中或通过该植入物局部释放。在一些实施方式中，可以使用控释系统。在一些实施方式中，可使用泵(参见Langer,supra；Sefton,1987.CRC Crit.Ref.Biomed.Eng.14:201；Buchwald et al.,1980.Surgery88:507；Saudeket al.,1989.N.Engl.J.Med.321:574)。在一些实施方式中，聚合物材料可用于促进和/或控制本发明突变RSV F分子的释放(参见Medical Applications of Controlled Release,Langer and Wise(eds.),1974。CRC Pres.,Boca Raton,Florida；Controlled DrugBioavailability,1984。Drug Product Design and Performance,Smolen and Ball(eds.),Wiley,New York；Ranger&Peppas,1983Macromol.Sci.Rev.Macromol.Chem.23:61；还参见Levy et al.,1985.Science 228:190；During et al,1989.Ann.Neurol.25:351；Howard et al.,1989.J.Neurosurg 71:105)。在一些实施方式中，可将控释系统放置到靠近要向其递送RSV预融合F蛋白或多肽的组织/器官处(参见，如Goodson,1984.MedicalApplications of Controlled Release,supra,vol.2:115 138)。Langer,1990,Science；vol.249:pp.527 1533描述了可与本发明结合使用的一些合适的控释系统。
在一些实施方式中，本发明组合物的施用可与一种或多种免疫刺激剂的施用一起执行。这种免疫刺激剂的非限制性示例包括，各种具有免疫刺激、免疫增强和促炎活性的细胞因子、淋巴因子和趋化因子，例如白介素(例如，IL-1、IL-2、IL-3、IL-4、IL-12、IL-13)；生长因子(例如，粒细胞-巨噬细胞(GM)-集落刺激因子(CSF))；以及其他免疫刺激剂，例如巨噬细胞炎性因子、Flt3配体、B7.1、B7.2。免疫刺激剂可以与突变RSV-F分子在同一配制物中施用，也可以单独施用。
在一些实施方式中，本发明的突变RSV F分子或包含它们的组合物，可以以各种不同的RSV疫苗接种方法或方案施用于受试者。在一些此类实施方式中，执行单剂施用。然而，在其它实施方式中，可通过相同或不同途径，施用额外的剂量来实现预期的预防效果。例如，在新生儿和婴儿中，可能需要多次施用才能引起足够水平的免疫力。如有必要维持对RSV感染足够程度的防护，可在整个儿童期每隔一段时间继续施用。同样，特别易受RSV感染的成年人，例如老年人和免疫受损者，可能需要多次免疫以建立和/或维持保护性免疫应答。诱导的免疫力水平，可以通过例如测量中和分泌和血清抗体的量来监测，并根据需要，调整剂量或重复接种疫苗，以引发和维持所需的保护水平。
在一些实施方式中，给药方案可包括单次施用/免疫。在其它实施方式中，给药方案可包括多次施用/免疫。例如，疫苗可以作为初次免疫接种，然后再进行一次或多次加强。在本发明的一些实施方式中，可以使用这种“初始-加强”疫苗接种方案。例如，在一些这类初始-加强方案中，包含本文所述突变RSV F分子的组合物可在间隔的时间多次(例如两次、三次或更多次)施用于个体，其中第一次施用是“初始”施用，随后的施用是“加强”施用。在其他这类初始-加强方案中，可在首先作为“初始”施用，向个体施用包含编码RSV多肽、蛋白质或蛋白质复合物的病毒或DNA载体的组合物，随后使用包含本文所述的RSV F多肽、蛋白质或蛋白质复合物的组合物进行一次或多次“加强”施用之后，向个体施用包含本文所述的突变RSV F分子的组合物。可通过与初次免疫相同和/或不同的途径递送加强剂。加强剂一般是在初次免疫或前一次施用加强剂后一段时间后施用。例如，可在初次免疫后大约两周或以上给予加强剂，和/或可在第一次加强后大约两周或以上给予第二次加强剂。加强剂可以在某个时间段内重复给予，例如，大约两周或更长时间，长达受试者的整个生命。加强可以间隔开的，例如，在初次免疫后或前一次加强后大约两周、大约三周、大约四周、大约一个月、大约两个月、大约三个月、大约四个月、大约五个月、大约六个月、大约七个月、大约八个月、大约九个月、大约十个月、大约十一个月、大约一年、大约一年半、大约两年、大约两年半、大约三年、大约三年半、大约四年、大约四年半、大约五年，或者更长时间。
在一些实施方式中，本发明的药物组合物可以方便地以单位剂型提供。单位剂型是指含有本发明突变RSV F分子的单一剂量或单位(例如有效量)，或其合适比例的剂型。单位剂型可存在于单一剂量或多剂量的容器。
在一些实施方式中，本发明的组合物可提供在密封的安瓿瓶或药水瓶中，并且可存储在冷冻干燥(冻干)条件下，仅需要在使用前添加无菌液体载体(例如水)。
试剂盒
本发明还提供了包含本发明突变RSV F分子，或包含该突变RSV F分子的组合物的试剂盒。为了便于使用本发明的方法和组合物，本文所述的任何组分和/或组合物，以及用于实验或治疗或疫苗接种目的的其他组分，可以试剂盒的形式包装。通常，除了上述组件外，试剂盒还包含其他材料，其可包括例如使用组件的说明书、包装材料、容器和/或递送装置。
表1-示例性的氨基酸序列
Figure BDA0002444986400000241
Figure BDA0002444986400000251
Figure BDA0002444986400000261
Figure BDA0002444986400000271
Figure BDA0002444986400000281
Figure BDA0002444986400000291
Figure BDA0002444986400000301
Figure BDA0002444986400000311
Figure BDA0002444986400000321
Figure BDA0002444986400000331
Figure BDA0002444986400000341
Figure BDA0002444986400000351
Figure BDA0002444986400000361
Figure BDA0002444986400000371
Figure BDA0002444986400000381
Figure BDA0002444986400000391
Figure BDA0002444986400000401
Figure BDA0002444986400000411
在表1中，SEQ ID NOs 1～91是示例性的WT和突变RSV F氨基酸序列，SEQ IDNOs92～96是可在RSV F分子的C-末端引入的示例性人工序列。对于SEQ ID NOs 1～91，带下划线的残基是F1和F2多肽，粗体字的残基是引入的突变，斜体字的残基是在一些实施方式中可以被移除或替换的残基，带双下划线的残基是人工引入的C-末端序列。
表2-示例性的RSV F氨基酸序列的概要
Figure BDA0002444986400000412
本发明的各实施方式也可通过以下非限制性实施例作进一步描述：
实施例1
选定的材料和方法
如下所述，突变RSV F蛋白在人细胞中表达，并通过引入二酪氨酸键进行修饰。
利用标准方法通过5’BamHI和3’XhoI限制性内切酶位点，将编码突变RSV-F分子的cDNA克隆到pCDNA3.1/zeo+表达载体(Invitrogen)中(见图1)。
将HEK 293细胞(ATCC)培养基在添加了10％胎牛血清和50μg/ml庆大霉素的杜尔贝科改良伊格尔培养基(DMEM，Invitrogen)中。将细胞接种于6孔组织培养板(Corning)中并培养至80％汇合(～24h)。按DNA与聚乙烯亚胺(25kDa，线性)比例为1:4(M/V)，每孔用2μg(微克)RSV-F表达质粒转染细胞。转染16h后，除去培养基，并替换成2ml/孔的无血清Freestyle-293表达培养基(Invitrogen)。细胞在37摄氏度下在5％CO2中再培养48～72h，然后进行收集和分析。
ELISA法检测细胞上清液中的RSV-F。收集后，在室温，在EIA/RIA高结合96孔板(Corning)中保持1h，从细胞上清液中直接捕获全部的RSV F蛋白。随后在室温，用含4％脱脂牛奶的PBS-吐温20(0.05％)保持1h，封闭含蛋白质和对照的孔。用PBS-T(400μl/孔)洗板3次。用高亲和力的人抗-hRSV抗体(在PBS中100ng/ml)，检测总RSV F，1h，该人抗-hRSV抗体识别RSV F的预融合和融合后两种形式。用识别位点
Figure BDA0002444986400000421
的pre-F特异性人单克隆抗体(在PBS中2μg/ml)检测预融合F。再次用PBS-T洗孔3次，然后与1:5000稀释在PBS中的缀合有HRP的山羊抗人F(ab)2(Jackson Immunoresearch)，在室温下孵育1h。用PBS-T洗孔6次，用100μl3,3',5,5'-四甲基联苯胺(TMB)产生比色信号，来检测和定量总RSV-F。加入等体积的4N硫酸终止比色反应。使用BioRad Benchmark Plus微孔板吸光度分光光度计，在450nm处测量最终的光密度读数。使用各上清液的2X连续稀释系列，来确定各样品的可检测信号的线性范围，以便准确比较RSV-F在样品间的相对量。
细胞上清液中的二酪氨酸交联。收集后，立即将100μl经转染的细胞和对照细胞上清液转移到黑色平底非结合96孔FIA板(Greiner bio-one)的孔中。将300ng多枝节霉菌(Arthromyces ramosus)过氧化物酶添加到要被交联的每个样品中。然后将1μl1.2mM H2O2添加到对照反应和DT反应中，使最终反应浓度为120μM H2O2。在室温下反应进行20分钟，然后加入等体积的pH 10的磷酸钠缓冲液使反应碱化。使用荧光和化学发光检测仪(ThermoScientific Fluoroskan Ascent FL)，在激发波长320nm和发射波长405nm下，读取二酪氨酸特异荧光。
转染后72小时，上清液经交联(DT)或未经交联，并且通过ELISA，用高亲和力的人抗-hRSV抗体(在PBS中100ng/ml)测量总蛋白，所述人抗-hRSV抗体能识别RSV-F预融合和融合后的形式。在一些实验中，在4℃保存16天后，通过ELISA，用识别位点
Figure BDA0002444986400000422
的preF特异性人单克隆抗体(在PBS中2μg/ml)测量位点
Figure BDA0002444986400000423
的显示情况。
实施例2
428Y、185Y、226Y突变RSV-F分子的制备及体外表征
图2提供了示例性突变RSV F分子的示意图，该示例性突变RSV F分子包含三个突变为酪氨酸的突变——428Y突变、185Y突变和226Y突变。这个示例性突变RSV F分子称为“AVR02”。AVR02的F0前体形式具有SEQ ID NO.81的氨基酸序列。成熟AVR02分子(在将编码SEQ ID NO.81的核酸分子转染并在细胞中表达后形成)包含SEQ ID NO.81的第26～109位和第137～568位氨基酸残基——其中第26～109位氨基酸残基为RSV F F2残基，第137～513位氨基酸残基为RSV F F1残基，第514～568位氨基酸残基是异源序列，并且包括折叠子(foldon)结构域、His标签、StrepII标签和凝血酶切割位点。来自第1～25位氨基酸的信号肽和来自第100～136位氨基酸的pep27肽不存在于最终成熟的三聚体AVR02分子中。
图4提供了制备经DT交联的AVR02(称为“DT-AVR02”)的方法的示意图。通过使用PEI的标准方法，将非交联AVR02瞬时转染到293Freestyle细胞(Invitrogen)中，并以分泌/可溶性形式表达5天。在第5天，在吊桶式转头中，通过低速离心旋转(1000×g×10min)收获细胞并沉淀成块，转移到第二个管中，用更高的速度旋转以澄清(3000×g×15min)，再次转移并通过70μm细胞过滤器，然后进行纯化。根据制造商的说明书，使用链霉凝集素树脂(IBALifesciences)纯化AVR02。使用含1mM EDTA和2.5mM脱硫生物素的PBS基洗脱缓冲液洗脱AVR02，使用切向流过滤系统(Pall公司)进行浓缩，并通过最终离心步骤(4度下，>20000×g×5min)进行澄清。
在含有150mM NaCl的磷酸盐缓冲液中，使用20～40μg/mL多枝节霉菌(Arthromyces ramosus)过氧化物酶和浓度为10～20μg/mL的AVR02进行交联反应。通过在39摄氏度，添加300～600μM H2O2开始反应，保持20分钟，并通过加入抗坏血酸(80ng/mL～50μg/mL)进行淬灭，此时添加咪唑至20mM。然后在IMAC色谱柱(Ni-NTA)上，用FPLC纯化AVR02蛋白以消除过氧化物酶，然后进行尺寸排除色谱(Superdex 200pg)，使用PBS作为洗脱剂。然后将含有AVR02的级分汇集在一起，浓缩至500μg/mL，并在4摄氏度，使用2单位/毫升生物素化凝血酶(Millipore)过夜切割(20小时)。然后按照制造商的说明书，清除凝血酶，并在室温，分批用链霉凝集素微珠孵育30分钟，消除任何未经切割的AVR02蛋白。然后，将蛋白质通过旋转过滤器以除去微珠，并在4摄氏度下旋转最后一次，然后进行最终的蛋白质定量测试。根据Starcher,B(Analytical Biochemistry 292:125-129(2001))的方法，最终的蛋白质测试是基于茚三酮的蛋白质测定法。蛋白质在液N2中速冻，使用前储存在-80摄氏度。
图3提供了，两种“设计”各自并入AVR02中形成二酪氨酸键的数据。图3A-在进行交联反应后，在2周内，在4℃，通过ELISA，使用D25(一种结合位点
Figure BDA0002444986400000431
的预融合特异性mAb)，测量通过198Y和226Y间的分子内交联(设计1)引入的稳定性。图3B-通过蛋白印迹，测定在185Y和428Y之间形成的分子间DT键(设计2)，并与WT进行比较(莫维珠单抗为一抗)。F1蛋白移向三聚体(TM)的大小。
图5A-B提供了，如基于位点IV/V抗体(图5A)和位点
Figure BDA0002444986400000432
抗体(图5B)的结合所确定的，与被称为DS-Cav1的RSV突变体(其记载于McLellan et al.(2013)Science342:592-598中，并且包含S155C、S290C、S190F和V207L突变)相比，AVR02和DT交联AVR02的构象完整性的数据。
图6A-B提供了DT-AVR02温度稳定性的数据。图6C提供了，在4℃保存5周后，AVR02在与
Figure BDA0002444986400000433
特异性mAb(5C4)结合方面没有表现出损失的数据。
实施例3
428Y、185Y、226Y突变RSV F分子在小鼠中的体内试验
进行了研究，以测试与DS-Cav1相比，DT交联AVR02(DT-AVR02)的免疫原性。上文描述了AVR02和DT-AVR02分子的细节。DS-Cav1突变体记载于McLellan et al.(2013)Science342:592-598中，并且包含S155C、S290C、S190F和V207L突变。按初始(第0天)-加强(第21天)方案，通过肌肉内注射对两组10只6～8周龄雌性无病原体的balb/c小鼠(Jackson Labs)进行免疫：第1组，每只动物每次注射10μg(微克)添加明矾佐剂的DT-AVR02；第2组，每只动物每次注射10μg(微克)添加明矾佐剂的DS-Cav1。在第35天，第二次免疫(加强)后两周，抽取血清。
热灭活血清在补充有谷氨酰胺(glutamax)、5％FBS和青霉素/链霉素的无酚MEM中稀释至1:800，并以4倍系列连续稀释(最终体积为50μl)。然后将RSV-Renilla荧光素酶病毒在与上述相同的培养基中稀释至2×104pfu/mL，并在每个孔(10000pfu/well)中加入50μL仅含病毒和含莫维珠单抗对照。病毒和血清在37摄氏度、5％CO2下孵育2小时。然后，Hep-2细胞(ATCC)经胰蛋白酶处理，计数，并在相同培养基中稀释至1×106细胞/mL，并向每个孔添加25μL(2.5×104细胞/孔)。然后将细胞在37摄氏度、5％CO2中孵育60～72小时，根据制造商的说明书，使用Renilla Glo荧光素酶检测系统(Promega)定量荧光素酶活性。采用非线性回归分析数据，以计算各血清稀释液的IC50浓度(Graphpad Prism)。
图7提供了本研究的结果——显示了用明矾负载的DS-Cav1或DT-AVR02接种的动物的RSV-RenillaLuc中和滴度。
实施例4
428Y、185Y、226Y突变RSV F分子在棉鼠中的体内试验
如在本实施例和附图中所用，术语“DT-preF”是指在前述实施例中“DT-AVR02”所指的分子，并且术语DT-preF可以与术语DT-AVR02互换使用。上文提供了DT-AVR02分子的结构及其制备方法的详细信息。
摘要/概述
本实验旨在评估DT-AVR02对棉鼠抗RSV的保护效果及安全性。还评估了添加佐剂(2％铝胶(ALH)，4mg/CR)的效果。采用初始-加强策略，通过肌肉内注射来施用疫苗。在RSV/A/Tracy攻击(第+35天)后，第+39天取右肺两(2)个较大肺叶的肺灌洗液和鼻冲洗液，并通过空斑测试确定RSV滴度。右肺的一(1)个肺叶在液氮中速冻并保存于-80℃。在整个实验过程中取血清样本，用于测量抗RSV/A/Tracy和抗RSV/B/18537的中和抗体活性。
与生理盐水对照相比，2和10μg两种剂量的DT-AVR02蛋白/棉鼠非常有效地将肺中的RSV/A/Tracy降低约4log10 PFU/g肺，将鼻中的RSV/A/Tracy降低约1.5log10总PFU。在这些幼稚棉鼠第二次(加强)接种后，所有疫苗均产生RSV/A/Tracy特异性中和抗体应答，且高于在第0天通过活RSV/A/Tracy感染所产生的中和抗体应答。
使用两种剂量方案，以2μg或10μg剂量施用的DT-AVR02(DT-preF)佐剂疫苗，在RSV幼稚棉鼠中提供了强大的免疫应答。2μg和10μg两种剂量均提供了在肺部抵抗RSV/A/Tracy复制的极好的防护作用，在鼻中显著但适度地减少了RSV/A/Tracy的复制，并引发了RSV/A/Tracy特异性和RSV/B/18537特异性的血清中和抗体。数据表明，这些疫苗在RSV免疫前人群中应该特别有效，例如老年成人人群。
实验设计、结果和结论的细节
我们设计并测试了一系列具有酪氨酸替换的RSV F突变体，能够引入靶向二酪氨酸(DT)交联，以将RSV F蛋白在构象上锁定于其预融合构象。其中一种分子在本文称为DT-AVR02(本文也称为DT-preF)。上文在其他实施例中，描述了该分子的结构和产生的细节。在小鼠上的初步研究(见前述实施例)表明，DT-AVR02至少在免疫原性方面等同于DS-Cav1，其是目前两种“最佳选择”之一，部分稳定化的preF设计(DS-Cav1和SC-DM)——同时显著提高的热稳定性。虽然DS-Cav1和SC-DM作为preF抗原已显示出良好的前景，但在4℃仅几周后，蛋白仍然相对不稳定并失去抗原性。我们的体外稳定性测试表明，DT-AVR02的热稳定性高于DS-Cav1和SC-DM，并且在37℃，其preF抗原性保持至少保持100小时。这表明，DT-AVR02可能对于临床开发足够稳定，而且其稳定性的提高也应能改善疫苗在体内的暴露和效力。
本实施例中所述实验的目的是，评估DT-AVR02/DT-preF RSV预融合F蛋白疫苗的两个剂量(2或10μg/CR)在棉鼠体内的效果。还评估了在配制物中添加佐剂2％铝胶(ALH)的效果。使用初始-加强策略，通过肌肉内注射接种疫苗。在RSV/A/Tracy攻击(第+35天)后，第+39天取右肺两(2)个较大肺叶的肺灌洗液和鼻冲洗液，并通过空斑试验测定RSV滴度。在整个实验过程中取血清样本，用于测定抗RSV/A/Tracy和抗RSV/B/18537的中和抗体活性。
使用图8所示的疫苗接种流程进行疫苗接种(IM)——其中在第0天进行疫苗接种，在第21天进行加强，14天后进行攻毒试验。
所有动物在第+35天接受活RSV/A/Tracy攻击。第1组，5只棉鼠(CR)IM注射生理盐水(作为阳性病毒感染对照)。第2组，5只CR在第0天用活RSV/A/Tracy感染(“黄金标准”)。第3组，5只CR用2μg DT-preF和100μg的2％ALH/CR佐剂进行IM注射。第4～5组，CR用10μg DT-preF和100μg的2％ALH/CR佐剂进行IM注射。
所用的棉鼠体重在约75～150g的范围内(在开始时的周龄测定)。实验结束时还测定了体重。在开始时，所有分组中的动物体重、年龄和性别分布都相似。在NIH和美国农业部的指南、关于实验动物的人道管理和利用的公共卫生服务政策下进行实验，实验方案为实验动物管理和使用委员会(IACUC)所批准。
将1.21×105PFU的RSV/A/Tracy(RSV/A/Tracy)(P3 w.p.3/13/2015)，鼻内施用(100μL)予经异氟烷轻度麻醉的棉鼠。接种后，在第0天(第2组)和第35天(所有组)，反滴定病毒接种物，以确定初始浓度(log10 TCID50/mL)。
铝胶(氢氧化铝凝胶；ALH)在室温下储存[21℃]。DT-AVR02储备蛋白在PBS中的浓度为160μg/mL(储存于-80℃)。所有步骤都在无菌罩下进行。以每只动物100μL的剂量使用2％铝胶制剂，共7剂(总计700μL)。
蛋白样品在湿冰上解冻。对于10μg剂量，蛋白质在PBS中稀释至浓度为105.26μg/mL(总计665μL，437μL DT PreF，228μL PBS)。对于2μg剂量，蛋白质在PBS中稀释至浓度为21.05μg/mL(总计665，87.4μL DT PreF，577.6μL PBS)。将蛋白样品翻转混合。用翻转法将铝胶(2％，Brenntag)充分混合。打开铝胶瓶，用移液管将35μL移到各剂量中，手充动分混合制成均匀的悬浮液。在接种之前，将配制好的溶液混合几次，并在每次注射之前重复混合以确保溶液均匀。
将DT-AVR02加佐剂(100μL DT-AVR02加ALH(第3、4组))注射(结核菌素注射器)至左胫骨前肌(TA)的区域(IM)。另一条腿用于第二次接种(第+21天加强)。
在第0天，从每组中的一只棉鼠的眼眶取血。在所有其他指定日，从所有棉鼠(5CR/组；4组)中取血。
用CO2安乐死后，将右肺结扎。从右肺取出两个肺叶，用无菌水冲洗去除外部血污并称重。同样的两个右叶使用含15％甘油混合2％FBS-MEM(1:1，v:v)的3mL伊斯科夫(Iscove)培养基(3mL注射器与26G3/8针头)经胸膜灌洗，并在多个部位注射使肺叶完全膨胀。通过轻轻按压一个膨胀肺叶来回收灌洗液，然后用同样的方法经胸膜灌洗另一个肺叶。收集洗涤液并保存在冰上直到滴定。对于上呼吸道的鼻冲洗液，使下颌脱臼。移除头部，将含15％甘油混合2％FBS-MEM(1:1，v:v)的1mL Iscove培养基推动通过每个鼻孔(总共2mL)。从托盘的后开口收集流出物，并保存在冰上直至滴定。样品在滴定之前不冷冻，在样品收集结束时进行滴定。保存一份血清样本用于抗体分析。
RSV Tracy肺灌洗液滴度(PFU/g肺)和鼻冲洗液滴度(总PFU)如下进行测定。在试验开始前24h，使用24孔组织培养板进行空斑试验，培养板中含有在10％FBS中制备的HEp-2细胞的近汇合单层(约2×105细胞/孔)。在每次试验开始时，对测试样品进行稀释(通常为连续log10)。然后将0.2mL的每种样品一式两份添加到孔中，然后吸附90分钟，期间偶尔轻轻摇动。移除接种物后，用含有抗生素、维生素和其他营养物质的0.75％甲基纤维素覆盖单层。每个试验都包括组织培养和阳性病毒对照。将板放置在36℃，5％CO2培养箱中。在第6天(+/-1天)，用0.01％结晶紫/10％福尔马林溶液(～1.5mL/孔)将板染色，并在室温下放置24～48h。用水洗孔。空斑出现时很容易看到(在深蓝色背景上有清晰的圆圈)。对含约20至100个之间空斑的孔内所有空斑进行计数、平均，将病毒滴度计算为：对于鼻冲洗液为总log10PFU，或对于肺或其他器官为log10 PFU/g组织。该方法的检测下限分别为0.70log10总PFU或约1.4log10 PFU/g肺组织。
在第0、21、35和39天，如下进行抗RSV中和抗体试验。在含HEp-2细胞的96孔微量滴定板上，对RSV/A/Tracy和RSV/B/18537的血清中和抗体进行检测。空斑纯化的RSV病毒用于微中和(Nt)试验。样品在56℃下热灭活30min。从3log2开始，一式两份进行两倍系列稀释，以测定每个样品的中和抗体(Ab)滴度。中和抗体滴度定义为血清稀释度，在该稀释度下观察到病毒细胞病变效应(CPE)降低≥50％。CPE定义为组织破坏，CPE可用10％中性缓冲福尔马林将孔固定并用结晶紫染色后目测。中和抗体(NtAb)滴度以绝对对数提供，而不是连续值。最低可检测NtAb滴度为2.5log2。具有不可检测Nt Ab滴度的样品被赋予2log2的值。NtAb滴度以0.5log2的倍数报告(例如，2.5、3.0、3.5、4.0等)。如果样品的NtAb滴度等于或超过测试上限(≥14log2)，则对该样品进行重新测试以便通过将稀释度延长至26log2来测定NtAb滴度。作为内部标准，帕利珠单抗的含量为40μg/mL。
通过ELISA测定RSV特异性抗体滴度。在进行ELISA试验之前，血清样品保存在-20℃。首先，对照组和疫苗组之间的病毒载量或RSV特异性中和抗体水平，通过log10转化病毒滴度或log2转化抗体滴度，使用Excel的双尾学生T检验(Microsoft Office 2013)进行分析。可以使用InStat3(GraphPad)，图基事后检验(post-hoc Tukey)比较法，通过ANOVA对额外的比较进行分析。
实验设计进一步细节见表A。结果总结如下。结果的进一步细节见下文，包括在表B-L中。
表A
Figure BDA0002444986400000461
缩写：ALH，2％Brenntag铝胶；PFU，空斑形成单位；Nt，中和。1N＝5只动物/组；共30只动物。2IM，施用途径。3所有动物用RSV/A/Tracy对进行攻击i.n.(100μL)。
表B：第+39天，各组肺部和体重
Figure BDA0002444986400000462
1两组间无统计学显著差异(学生T检验，双尾)。2两组间无统计学显著差异(学生T检验，双尾)。
表C：第+39天，鼻冲洗液中的RSV/A/Tracy滴度
Figure BDA0002444986400000471
*最低检测限＝0.70log10总PFU。d，死亡。为了统计分析(学生T检验，双尾)，未稀释样品中的0个空斑计算为0.40log10总PFU。有附加显著性P值：第2组v第3、4组；分别地P＝0.00004、0.00024(学生T检验，双尾)。
表D：第+39天，肺灌洗液中的RSV/A/Tracy滴度
Figure BDA0002444986400000472
*最低检测限～1.4log10 PFU/g肺。d，死亡。为了统计分析(学生T检验，双尾)，未稀释样品中的0个空斑为在0.90～1.04log10 PFU/g肺的范围内。没有额外的显著性P值(学生T检验，双尾)。
表E：第0天，RSV/A/Tracy血清中和滴度
Figure BDA0002444986400000473
*学生T检验，双尾。最低检测限＝2.5；为了统计分析，<2.5的值计为2。
表F：第+21天，RSV/A/Tracy血清中和滴度
Figure BDA0002444986400000474
*学生T检验，双尾。最低检测限＝2.5；为了统计分析，<2.5的值计为2。额外的显著性P值(学生T检验，双尾)：第2组v第3、4组，P≤0.0036。d，死亡。
表G：第+35天，RSV/A/Tracy血清中和滴度
Figure BDA0002444986400000481
*学生T检验，双尾。最低检测限＝2.5；为了统计分析，<2.5的值计为2。额外的显著性P值(学生T检验，双尾)：第2组v第3、4组，P<0.044；d，死亡。
表H：第+39天，RSV/A/Tracy血清中和滴度
Figure BDA0002444986400000482
*学生T检验，双尾。最低检测限＝2.5；为了统计分析，<2.5的值计为2。额外的显著性P值(学生T检验，双尾)：第2组v第3、4组，P≤0.045；d，死亡。
表I：第0天，RSV/B/18537血清中和滴度
Figure BDA0002444986400000483
*学生T检验，双尾。最低检测限＝2.5；为了统计分析，<2.5的值计为2。
表J：第+21天，RSV/B/18537血清中和滴度
Figure BDA0002444986400000484
*学生T检验，双尾。最低检测限＝2.5；为了统计分析，<2.5的值计为2。没有额外的显著性P值(学生T检验，双尾)。
表K：第+35天，RSV/B/18537血清中和滴度
Figure BDA0002444986400000491
*学生T检验，双尾。最低检测限＝2.5；为了统计分析，<2.5的值计为2。额外的显著性P值(学生T检验，双尾)：第2组v第3、4组，P≤0.015。
表L：第+39天，RSV/B/18537血清中和滴度
Figure BDA0002444986400000492
*学生T检验，双尾。最低检测限＝2.5；为了统计分析，<2.5的值计为2。额外的显著性P值(学生T检验，双尾)：第2组v第3、4组，P<0.013。
棉鼠2B在第9天发现死在笼子里。死因不明。
含2％铝胶佐剂的DT-preF/DT-AVR02，对鼻冲洗液中RSV/A/Tracy滴度的影响：与生理盐水对照(第1组)相比，第0天感染活RSV/A/Tracy(第2组)使滴度降低了4.42log10总PFU(P<0.00001；学生T检验，双尾)(图9，表B)。所有疫苗组合均将病毒滴度降低了1.37到1.77log10总PFU(P≤0.00024；学生T检验，双尾)。两种疫苗组合之间没有统计学差异。
含2％铝胶佐剂的DT-preF/DT-AVR02对肺灌洗液中RSV/A/Tracy滴度的影响：与生理盐水对照(第1组)相比，第0天感染活RSV/A/Tracy(第2组)使滴度降低至检测限以下(4.03log10 PFU/g肺；P<0.00001；学生T检验，双尾)(图10，表C)。第3组和第4组的疫苗组合的RSV滴度降低到检测限以下(4.04～4.13log10 PFU/g肺；P<0.00001；学生T检验，双尾)。两种疫苗组合之间没有统计学差异。
含2％铝胶佐剂的的DT-preF/DT-AVR02对RSV/A/Tracy或RSV/B/18537特异性中和抗体产生的影响：对于RSV/A/Tracy特异性中和抗体(NtAb)，用活RSV/A/Tracy(第2组)自然感染至第21天产生NtAb(约5.5log2/0.05mL)并在第39天仍保持在该水平(图11；表D～G)。在第21天，与任何DT-AVR02疫苗都有统计学差异(P≤0.0036；学生T检验，双尾)。然而，在第21天第二次疫苗接种之后，所有疫苗都有强大的NtAb应答，高于活RSV/A/Tracy感染。
通过活RSV/A/Tracy感染和2种疫苗，产生RSV/B/1853交叉反应性NtAb(图12；表H～L)。两种疫苗的NtAb应答模式与RSV/A/Tracy的相似，但1-2log2水平较低。
实施例5
428Y和427Y突变RSV-F分子的体外和体内比较
使用前述实施例中描述的方法，产生两种稳定处于pre-F构象的DT交联突变RSV F分子。这两种突变体的区别仅在于一种在氨基酸428处有突变为酪氨酸的点突变(428Y突变)，另一种在氨基酸427处有突变为酪氨酸的点突变(427Y突变)。这两种分子均包括S190F和V207L突变(即“Cav1”突变)，在第185和226位氨基酸残基处突变为酪氨酸的突变(即185Y突变和226Y突变)。
428Y突变体(包括V185Y、K428Y、K226Y、S190F和V207L突变)在本文中可互换地称为“428Y突变体”或“DT-AVR02”。428Y突变体的F0前体形式具有SEQ ID NO.81的氨基酸序列。成熟428Y突变分子(在编码SEQ ID NO.81的核酸分子转染并在细胞中表达后形成)包含SEQ ID NO.81的第26～109位和第137～568位氨基酸残基——其中第26～109位氨基酸残基为RSV F F2残基，第137～513位氨基酸残基为RSV F F1残基，第514～568位氨基酸残基为异源序列，并包含折叠子(foldon)结构域、His标签、StrepII标签和凝血酶切割位点。最终成熟的三聚体428Y突变分子中不存在来自第1～25位氨基酸的信号肽和来自第100～136位氨基酸的pep27肽。
427Y突变体(包括V185Y、K427Y、K226Y，S190F和V207L突变)在此可互换地称为“427Y突变”或“DT-CAV1”。428Y突变体的F0前体形式具有SEQ ID NO.81的氨基酸序列，但它包含在第428位氨基酸处的赖氨酸(K)残基和在第427位氨基酸处的酪氨酸。成熟427Y突变分子(在编码该SEQ ID NO.81修改型式的核酸分子转染并在细胞中表达后形成)包含该修改序列的第26～109位和第137～568位氨基酸残基——其中第26～109位氨基酸残基为RSVF F2残基，第137～513位氨基酸残基为RSV F F1残基，第514～568位氨基酸残基为异源序列，并包括折叠子(foldon)结构域、His标签、StrepII标签和凝血酶切割位点。最终成熟的三聚体427Y突变分子中不存在来自第1～25位氨基酸的信号肽和来自第100～136位氨基酸的pep27肽。
根据上述方法表达和纯化427Y和428Y突变体，并经由ELISA分析构象完整性，其中使用莫维珠单抗，对总蛋白进行标准化，并用构象5C4(位点
Figure BDA0002444986400000501
预融合特异性)抗体，以及结合抗原位点IV和V之间区域的预融合特异性单克隆抗体。使用Ni-NTA涂布板(Qiagen)，用一步TMB试剂(Pierce)对测试进行显色。如图13所示，取代K427Y的N428Y替换显著提高了与位点IV-V抗体的结合(图13B和D)，也提高了与位点
Figure BDA0002444986400000502
抗体的结合(图13A&C)。
N428Y取代K427Y也影响了分子在交联反应后的聚集状态。根据本文其他地方描述的方法纯化蛋白质，并且两种蛋白质在相同条件下并如本文其他地方描述的方法进行交联。在PBS用作洗脱剂的Superdex 200 26/60pg柱尺寸排除色谱中，交联物质的色谱图明显不同。如图14A所示，在交联反应之后，427Y突变体(DT-CAV1)主要产生了高阶聚集体种类，如图14和最终产物的相应考马斯染色SDS-PAGE分析(图14C，左边两个凝胶条)所示。当通过相同过程来产生428Y突变体(DT-AVR02)时，大多数蛋白质处于三聚体级分中，如色谱图(图14B)和最终产物的相应考马斯染色SDS-PAGE凝胶(图14C，右边凝胶条)所证明的。
还进行了研究，以测试427Y突变体(DT-CAV1)、427Y突变体(DT-AVR02)和McLellan等(2013)Science 342:592-598(其包括S155C、S290C、S190F和V207L突变)中描述的DS-Cav1突变体的免疫原性。两组10只6～8周龄、无病原体的雌性CB6/F1J小鼠(Jackson Labs)按初始(第0天)-加强(第21天)方案进行免疫：在研究中，第1组均接种了10μg(微克)添加明矾佐剂的DS-Cav1，而第2组在第一个研究中，每只动物接种了10μg(微克)，单位剂量添加明矾佐剂的427Y突变体(DT-CAV1)，在第二个研究中，每只动物接种10μg(微克)，单位剂量添加明矾佐剂的428Y突变体(DT-AVR02)。在第35天，第二次疫苗接种(加强)后两周，收集血清。结果如图15A-B所示，表明接种428Y突变体(DT-AVR02)动物的血清中和滴度(图15B)明显高于接种427Y突变体(DT-Cav1)的动物(图15A)。
实施例6
含蔗糖的配制物减少RSV-F聚集体的形成
已经发现，在本发明突变RSV F分子的配方中加入蔗糖，可显著减少不期望的聚集体的形成。使用上述示例性DT交联428Y突变体(DT-AVR02)进行实验。最终浓缩后，分析尺寸排除色谱法(SEC)证明，存在所需DT-AVR02三聚体(图16A的峰C)和聚集体(图16A的峰A和峰B)。在纯化步骤的洗脱过程中，用10％蔗糖配制DT-AVR02分子似乎消除了聚集体的形成。如图16B所示，在用蔗糖配制的样品中，峰C(三聚体)仍然存在，但峰A和峰B(聚集体)不明显。
实施例7
AVR02在非人灵长类动物中的体内测试
六组5只非人灵长类动物，通过肌肉内注射按初始(第0天)-加强(第28天)方案进行免疫。第1、2组分别接种含(第1组)和不含(第2组)佐剂的高剂量(50mg/每只动物/注射)DT-AVR02；第3、4组分别接种含(第3组)和不含(第4组)佐剂的低剂量(10mg/每只动物/注射)DT-AVR02；第5、6组分别接种含(第1组)和不含(第2组)佐剂的高剂量(50mg/每只动物/注射)我们的对比物DS-Cav1。
所有组的动物分别在第0天和第28天注射两次。在第0天初始免疫前和第28天二次免疫前，从所有动物身上取血。在第42天和第49天再次抽取/收集血液。通过标准方法分离外周血单核细胞，以表征RSV特异性T细胞应答的频率和表型(Th1/Th2)；分析血清以定量NHP抗F应答(IgM、总IgG、IgG1、IgG2、IgG3)，通过标准方法(位点
Figure BDA0002444986400000511
和位点II)进行竞争分析来进行表位分析，还通过标准方法对中和滴度进行定量。
实施例8
AVR02的I期人体临床试验
进行了随机、安慰剂对照、观察者单盲、剂量范围递增的研究，以评估单独或含明矾佐剂的，稳定化预融合RSV F亚基蛋白疫苗DT-AVR02，在健康(非怀孕)成人(18至50岁)中的安全性、耐受性和免疫原性。
150名受试者分布在7个队列中，测试6种配方和一种安慰剂。受试者按4:1的比例随机分配到疫苗处理组或生理盐水安慰剂组，因此每个队列包括20名接受活性疫苗的受试者(A、B、C、D、E和F组)和5名接受安慰剂的受试者(G组)。6组20人(活性疫苗)和5人(安慰剂)受试者接受测试。6×25＝150名受试者。低、中、高剂量(每次注射50mcg、150mcg和500mcg)，每种剂量以含明矾作为佐剂和不含明矾佐剂来配制。
受试者IM注射两次：第0天和第90天(+/-5天)。从每次疫苗接种(第0天和第90天)到疫苗接种后30天，对受试者所有副作用(AE)进行跟踪，包括严重AE(SAE)和非严重AEs。此外，在第60、150、180、210天和第310天通过电话联系受试者，询问是否出现SAE和重大的新的医疗状况。
主要目的是评估对健康成人IM注射时，单独或含明矾的三种剂量DT-AVR02的安全性、反应原性和耐受性，监测超过44周。第二个目标是评估受试者对三种剂量的未添加和添加佐剂的DT-AVR02的抗体应答，其测量方法为：通过ELISA评估总Ab反应(包括Ab亚型分析)，每次注射后2周和4周后通过竞争ELISA评估表位特异性反应，每次注射后2周和4周后进行中和试验。
***
虽然为了清楚和理解的目的，已经对上述发明进行了一些详细的描述，但是本领域技术人员可以从本公开的阅读中清楚地看到，可以在不脱离本发明真实范围的情况下对形式和细节进行各种改变。本发明还可以根据以下权利要求书进行进一步的定义。
序列表
<110> 阿凡达医疗有限责任公司
<120> 构象稳定化的RSV预融合F蛋白
<130> AVATAR.009.WO1
<140>
<141>
<150> 62/674,791
<151> 2018-05-22
<150> 62/640,467
<151> 2018-03-08
<150> 62/629,685
<151> 2018-02-12
<150> 62/542,247
<151> 2017-08-07
<160> 96
<170> PatentIn 3.5版
<210> 1
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 1
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Pro Thr Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Val Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Ile Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Met Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Ala Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Ile Leu Leu Ser Leu Ile Ala Val
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Arg Ser Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Asn
565 570
<210> 2
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 2
Met Glu Leu Pro Ile Leu Lys Thr Asn Ala Ile Thr Thr Ile Leu Ala
1 5 10 15
Ala Val Thr Leu Cys Phe Ala Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Ala Asn Ser Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Thr Lys Asn Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Ile
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Ala Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Ile Leu Leu Ala Leu Ile Ala Val
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Arg Ser Thr Pro Val Ile Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Asn
565 570
<210> 3
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 3
Met Glu Leu Pro Ile Leu Lys Thr Asn Ala Ile Thr Thr Ile Leu Ala
1 5 10 15
Ala Val Thr Leu Cys Phe Ala Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Thr Lys Asn Thr Asn Val Thr
115 120 125
Val Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Ile
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Ala Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Ile Leu Leu Ser Leu Ile Ala Val
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Arg Ser Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Asn
565 570
<210> 4
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 4
Met Glu Leu Pro Ile Leu Lys Thr Asn Ala Ile Thr Thr Ile Leu Ala
1 5 10 15
Ala Val Thr Leu Cys Phe Ala Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Thr Lys Asn Thr Asn Val Thr
115 120 125
Val Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Ile
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Ala Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Ile Leu Leu Ser Leu Ile Ala Val
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Arg Ser Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Asn
565 570
<210> 5
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 5
Met Glu Leu Pro Ile Leu Lys Thr Asn Ala Ile Thr Thr Ile Leu Ala
1 5 10 15
Ala Val Thr Leu Cys Phe Ala Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Gln Ala Ala Asn Ser Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Thr Lys Asn Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Ile
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Ala Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Ile Leu Leu Ser Leu Ile Ala Val
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Arg Ser Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Asn
565 570
<210> 6
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 6
Met Glu Leu Pro Ile Ile Lys Ala Asn Ala Ile Thr Thr Ile Leu Ile
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Thr Ala Ala Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Ile
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Ala Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Ile Leu Leu Ser Leu Ile Ala Val
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Arg Ser Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Asn
565 570
<210> 7
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 7
Met Glu Leu Pro Ile Leu Lys Thr Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Thr Lys Asn Asn Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Val Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Ile Leu Leu Leu Leu Ile Ala Val
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Arg Ser Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Asn
565 570
<210> 8
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 8
Met Glu Leu Pro Ile Leu Lys Thr Asn Ala Ile Thr Thr Ile Phe Ala
1 5 10 15
Ala Val Thr Leu Cys Phe Ala Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Thr Lys Asn Asn Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Ile
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Val Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Ile Leu Leu Leu Leu Ile Ala Val
530 535 540
Gly Leu Phe Leu Tyr Cys Lys Ala Arg Ser Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Glu Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Asn
565 570
<210> 9
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 9
Met Glu Leu Pro Ile Leu Lys Thr Asn Ala Ile Thr Thr Ile Phe Ala
1 5 10 15
Ala Val Thr Leu Cys Phe Ala Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Val Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Thr Lys Asn Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Ile
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Ala Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Ile Leu Leu Ser Leu Ile Ala Val
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Arg Ser Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Asn
565 570
<210> 10
<211> 568
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 10
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Val Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu Ser Ala Ile Gly Gly Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln
515 520 525
Ala Tyr Val Arg Lys Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu
530 535 540
Gly Gly Leu Val Pro Arg Gly Ser His His His His His His Ser Ala
545 550 555 560
Trp Ser His Pro Gln Phe Glu Lys
565
<210> 11
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 11
Met Glu Leu Leu Ile His Arg Ser Ser Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Val Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Phe Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln Tyr Met Asn Tyr Thr Ile Asn Thr Thr Lys Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Arg Leu Leu Pro Ile Val Asn
195 200 205
Gln Gln Ser Cys Arg Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Met Asn Ser Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Ile Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Ile Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Arg Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Lys
565 570
<210> 12
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 12
Met Glu Leu Leu Ile His Arg Ser Ser Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Ile Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Phe Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln Tyr Met Asn Tyr Thr Ile Asn Thr Thr Lys Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Gln Leu Leu Pro Ile Val Asn
195 200 205
Gln Gln Ser Cys Arg Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Ser Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Ile Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Ile Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Arg Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Ala Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Lys
565 570
<210> 13
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 13
Met Glu Leu Leu Ile His Arg Ser Ser Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Ile Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Phe Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln Tyr Met Asn Tyr Thr Ile Asn Thr Thr Lys Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Arg Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Ser Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Ile Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Arg Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Ala Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Lys
565 570
<210> 14
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 14
Met Glu Leu Leu Ile His Arg Ser Ser Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Ile Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Val Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln Tyr Met Asn Tyr Thr Ile Asn Thr Thr Lys Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Gln Leu Leu Pro Ile Val Asn
195 200 205
Gln Gln Ser Cys Arg Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Ser Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Tyr Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Ile Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Arg Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Ala Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Lys
565 570
<210> 15
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 15
Met Glu Leu Leu Ile His Arg Ser Ser Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Val Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Phe Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln Tyr Met Asn Tyr Thr Ile Asn Thr Thr Lys Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Met Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Ile Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Arg Leu Leu Pro Ile Val Asn
195 200 205
Gln Gln Ser Cys Arg Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Ser Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Ile Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Ile Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Arg Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Lys
565 570
<210> 16
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 16
Met Glu Leu Leu Ile His Arg Ser Ser Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Ile Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Phe Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln Tyr Met Asn Tyr Thr Ile Asn Thr Thr Lys Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Gln Leu Leu Pro Ile Val Asn
195 200 205
Gln Gln Ser Cys Arg Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Ser Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Met Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Ile Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Ile Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Arg Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Val Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Lys
565 570
<210> 17
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 17
Met Glu Leu Leu Ile His Arg Ser Ile Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Ile Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Phe Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Thr Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln Tyr Met Asn Tyr Thr Ile Asn Thr Thr Lys Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Gln Leu Leu Pro Ile Val Asn
195 200 205
Gln Gln Ser Cys Arg Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Ser Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Ile Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Ile Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Arg Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Val Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Ala Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Lys
565 570
<210> 18
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 18
Met Glu Leu Leu Val His Arg Ser Ser Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Ile Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Phe Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln Tyr Met Asn Tyr Thr Ile Asn Thr Thr Asn Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Gln Leu Leu Pro Ile Val Asn
195 200 205
Gln Gln Ser Cys Arg Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Ser Arg Leu Leu Glu Ile Ala Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Ile Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Ile Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Arg Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Ala Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Lys
565 570
<210> 19
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 19
Met Glu Leu Leu Ile His Arg Ser Ser Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Val Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Phe Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln Tyr Met Asn Tyr Thr Ile Asn Thr Thr Lys Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Arg Leu Leu Pro Ile Val Asn
195 200 205
Gln Gln Ser Cys Arg Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Met Asn Ser Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Ile Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Ile Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Arg Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Lys
565 570
<210> 20
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 20
Met Glu Leu Leu Ile His Arg Ser Ser Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Ile Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Phe Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Thr Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln His Met Asn Tyr Thr Ile Asn Thr Thr Lys Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Gln Leu Leu Pro Ile Val Asn
195 200 205
Gln Gln Ser Cys Arg Ile Phe Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Ser Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Ile Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Ile Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Lys
565 570
<210> 21
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 21
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Pro Thr Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Val Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Ile Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Met Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Ala Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Ile Leu Leu Ser Leu Ile Ala Val
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Arg Ser Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Asn
565 570
<210> 22
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 22
Met Glu Leu Pro Ile Leu Lys Thr Asn Ala Ile Thr Thr Ile Leu Ala
1 5 10 15
Ala Val Thr Leu Cys Phe Ala Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Ala Asn Ser Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Thr Lys Asn Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Ile
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Ala Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Ile Leu Leu Ala Leu Ile Ala Val
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Arg Ser Thr Pro Val Ile Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Asn
565 570
<210> 23
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 23
Met Glu Leu Pro Ile Leu Lys Thr Asn Ala Ile Thr Thr Ile Leu Ala
1 5 10 15
Ala Val Thr Leu Cys Phe Ala Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Thr Lys Asn Thr Asn Val Thr
115 120 125
Val Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Ile
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Ala Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Ile Leu Leu Ser Leu Ile Ala Val
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Arg Ser Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Asn
565 570
<210> 24
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 24
Met Glu Leu Pro Ile Leu Lys Thr Asn Ala Ile Thr Thr Ile Leu Ala
1 5 10 15
Ala Val Thr Leu Cys Phe Ala Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Thr Lys Asn Thr Asn Val Thr
115 120 125
Val Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Ile
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Ala Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Ile Leu Leu Ser Leu Ile Ala Val
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Arg Ser Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Asn
565 570
<210> 25
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 25
Met Glu Leu Pro Ile Leu Lys Thr Asn Ala Ile Thr Thr Ile Leu Ala
1 5 10 15
Ala Val Thr Leu Cys Phe Ala Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Gln Ala Ala Asn Ser Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Thr Lys Asn Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Ile
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Ala Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Ile Leu Leu Ser Leu Ile Ala Val
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Arg Ser Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Asn
565 570
<210> 26
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 26
Met Glu Leu Pro Ile Ile Lys Ala Asn Ala Ile Thr Thr Ile Leu Ile
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Thr Ala Ala Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Ile
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Ala Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Ile Leu Leu Ser Leu Ile Ala Val
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Arg Ser Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Asn
565 570
<210> 27
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 27
Met Glu Leu Pro Ile Leu Lys Thr Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Thr Lys Asn Asn Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Val Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Ile Leu Leu Leu Leu Ile Ala Val
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Arg Ser Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Asn
565 570
<210> 28
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 28
Met Glu Leu Pro Ile Leu Lys Thr Asn Ala Ile Thr Thr Ile Phe Ala
1 5 10 15
Ala Val Thr Leu Cys Phe Ala Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Thr Lys Asn Asn Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Ile
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Val Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Ile Leu Leu Leu Leu Ile Ala Val
530 535 540
Gly Leu Phe Leu Tyr Cys Lys Ala Arg Ser Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Glu Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Asn
565 570
<210> 29
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 29
Met Glu Leu Pro Ile Leu Lys Thr Asn Ala Ile Thr Thr Ile Phe Ala
1 5 10 15
Ala Val Thr Leu Cys Phe Ala Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Val Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Thr Lys Asn Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Ile
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Ala Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Ile Leu Leu Ser Leu Ile Ala Val
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Arg Ser Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Asn
565 570
<210> 30
<211> 568
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 30
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Val Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu Ser Ala Ile Gly Gly Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln
515 520 525
Ala Tyr Val Arg Lys Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu
530 535 540
Gly Gly Leu Val Pro Arg Gly Ser His His His His His His Ser Ala
545 550 555 560
Trp Ser His Pro Gln Phe Glu Lys
565
<210> 31
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 31
Met Glu Leu Pro Ile Leu Lys Thr Asn Ala Ile Thr Thr Ile Phe Ala
1 5 10 15
Ala Val Thr Leu Cys Phe Ala Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Val Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Thr Lys Asn Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Ile
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Ala Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Ile Leu Leu Ser Leu Ile Ala Val
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Arg Ser Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Asn
565 570
<210> 32
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 32
Met Glu Leu Leu Ile His Arg Ser Ser Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Ile Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Phe Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln Tyr Met Asn Tyr Thr Ile Asn Thr Thr Lys Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Gln Leu Leu Pro Ile Val Asn
195 200 205
Gln Gln Ser Cys Arg Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Ser Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Ile Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Ile Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Arg Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Ala Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Lys
565 570
<210> 33
<211> 573
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 33
Met Glu Leu Leu Ile His Arg Ser Ser Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Ile Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Phe Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln Tyr Met Asn Tyr Thr Ile Asn Thr Thr Lys Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Arg Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Ser Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Ile Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Arg Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Ala Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser
565 570
<210> 34
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 34
Met Glu Leu Leu Ile His Arg Ser Ser Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Ile Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Val Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln Tyr Met Asn Tyr Thr Ile Asn Thr Thr Lys Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Gln Leu Leu Pro Ile Val Asn
195 200 205
Gln Gln Ser Cys Arg Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Ser Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Tyr Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Ile Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Arg Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Ala Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Lys
565 570
<210> 35
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 35
Met Glu Leu Leu Ile His Arg Ser Ser Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Ile Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Val Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln Tyr Met Asn Tyr Thr Ile Asn Thr Thr Lys Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Gln Leu Leu Pro Ile Val Asn
195 200 205
Gln Gln Ser Cys Arg Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Ser Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Tyr Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Ile Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Arg Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Ala Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Lys
565 570
<210> 36
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 36
Met Glu Leu Leu Ile His Arg Ser Ser Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Ile Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Phe Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln Tyr Met Asn Tyr Thr Ile Asn Thr Thr Lys Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Gln Leu Leu Pro Ile Val Asn
195 200 205
Gln Gln Ser Cys Arg Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Ser Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Met Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Ile Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Ile Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Arg Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Val Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Lys
565 570
<210> 37
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 37
Met Glu Leu Leu Ile His Arg Ser Ile Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Ile Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Phe Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Thr Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln Tyr Met Asn Tyr Thr Ile Asn Thr Thr Lys Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Gln Leu Leu Pro Ile Val Asn
195 200 205
Gln Gln Ser Cys Arg Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Ser Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Ile Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Ile Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Arg Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Val Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Ala Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Lys
565 570
<210> 38
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 38
Met Glu Leu Leu Val His Arg Ser Ser Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Ile Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Phe Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln Tyr Met Asn Tyr Thr Ile Asn Thr Thr Asn Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Gln Leu Leu Pro Ile Val Asn
195 200 205
Gln Gln Ser Cys Arg Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Ser Arg Leu Leu Glu Ile Ala Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Ile Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Ile Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Arg Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Ala Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Lys
565 570
<210> 39
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 39
Met Glu Leu Leu Ile His Arg Ser Ser Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Val Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Phe Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln Tyr Met Asn Tyr Thr Ile Asn Thr Thr Lys Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Arg Leu Leu Pro Ile Val Asn
195 200 205
Gln Gln Ser Cys Arg Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Met Asn Ser Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Ile Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Ile Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Arg Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Lys
565 570
<210> 40
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 40
Met Glu Leu Leu Ile His Arg Ser Ser Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Ile Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Phe Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Thr Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln His Met Asn Tyr Thr Ile Asn Thr Thr Lys Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Gln Leu Leu Pro Ile Val Asn
195 200 205
Gln Gln Ser Cys Arg Ile Phe Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Ser Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Ile Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Ile Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Lys
565 570
<210> 41
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 41
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Pro Thr Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Val Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Tyr Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Tyr Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Ile Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Met Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Ala Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Ile Leu Leu Ser Leu Ile Ala Val
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Arg Ser Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Asn
565 570
<210> 42
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 42
Met Glu Leu Pro Ile Leu Lys Thr Asn Ala Ile Thr Thr Ile Leu Ala
1 5 10 15
Ala Val Thr Leu Cys Phe Ala Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Ala Asn Ser Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Thr Lys Asn Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Tyr Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Tyr Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Ile
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Ala Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Ile Leu Leu Ala Leu Ile Ala Val
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Arg Ser Thr Pro Val Ile Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Asn
565 570
<210> 43
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 43
Met Glu Leu Pro Ile Leu Lys Thr Asn Ala Ile Thr Thr Ile Leu Ala
1 5 10 15
Ala Val Thr Leu Cys Phe Ala Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Thr Lys Asn Thr Asn Val Thr
115 120 125
Val Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Tyr Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Tyr Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Ile
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Ala Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Ile Leu Leu Ser Leu Ile Ala Val
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Arg Ser Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Asn
565 570
<210> 44
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 44
Met Glu Leu Pro Ile Leu Lys Thr Asn Ala Ile Thr Thr Ile Leu Ala
1 5 10 15
Ala Val Thr Leu Cys Phe Ala Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Thr Lys Thr Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Tyr Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Tyr Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Ala Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Ile Leu Leu Ser Leu Ile Ala Val
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Arg Ser Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Ser
565 570
<210> 45
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 45
Met Glu Leu Pro Ile Leu Lys Thr Asn Ala Ile Thr Thr Ile Leu Ala
1 5 10 15
Ala Val Thr Leu Cys Phe Ala Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Gln Ala Ala Asn Ser Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Thr Lys Asn Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Tyr Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Tyr Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Ile
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Ala Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Ile Leu Leu Ser Leu Ile Ala Val
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Arg Ser Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Asn
565 570
<210> 46
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 46
Met Glu Leu Leu Val His Arg Ser Ser Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Ile Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Phe Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln Tyr Met Asn Tyr Thr Ile Asn Thr Thr Asn Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Tyr Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Gln Leu Leu Pro Ile Val Asn
195 200 205
Gln Gln Ser Cys Arg Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Tyr Asn Ser Arg Leu Leu Glu Ile Ala Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Ile Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Ile Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Arg Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Ala Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Lys
565 570
<210> 47
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 47
Met Glu Leu Pro Ile Leu Lys Thr Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Thr Lys Asn Asn Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Tyr Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Tyr Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Val Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Ile Leu Leu Leu Leu Ile Ala Val
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Arg Ser Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Asn
565 570
<210> 48
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 48
Met Glu Leu Pro Ile Leu Lys Thr Asn Ala Ile Thr Thr Ile Phe Ala
1 5 10 15
Ala Val Thr Leu Cys Phe Ala Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Thr Lys Asn Asn Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Tyr Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Tyr Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Ile
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Val Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Ile Leu Leu Leu Leu Ile Ala Val
530 535 540
Gly Leu Phe Leu Tyr Cys Lys Ala Arg Ser Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Glu Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Asn
565 570
<210> 49
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 49
Met Glu Leu Pro Ile Leu Lys Thr Asn Ala Ile Thr Thr Ile Phe Ala
1 5 10 15
Ala Val Thr Leu Cys Phe Ala Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Val Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Thr Lys Asn Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Tyr Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Tyr Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Ile
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Ala Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Ile Leu Leu Ser Leu Ile Ala Val
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Arg Ser Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Asn
565 570
<210> 50
<211> 568
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 50
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Val Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Tyr Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Tyr Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu Ser Ala Ile Gly Gly Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln
515 520 525
Ala Tyr Val Arg Lys Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu
530 535 540
Gly Gly Leu Val Pro Arg Gly Ser His His His His His His Ser Ala
545 550 555 560
Trp Ser His Pro Gln Phe Glu Lys
565
<210> 51
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 51
Met Glu Leu Leu Ile His Arg Ser Ser Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Val Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Phe Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln Tyr Met Asn Tyr Thr Ile Asn Thr Thr Lys Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Tyr Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Arg Leu Leu Pro Ile Val Asn
195 200 205
Gln Gln Ser Cys Arg Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Tyr Asn Ser Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Ile Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Ile Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Arg Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Lys
565 570
<210> 52
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 52
Met Glu Leu Leu Ile His Arg Ser Ser Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Ile Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Phe Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln Tyr Met Asn Tyr Thr Ile Asn Thr Thr Lys Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Tyr Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Gln Leu Leu Pro Ile Val Asn
195 200 205
Gln Gln Ser Cys Arg Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Tyr Asn Ser Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Ile Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Ile Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Arg Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Ala Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Lys
565 570
<210> 53
<211> 573
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 53
Met Glu Leu Leu Ile His Arg Ser Ser Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Ile Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Phe Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln Tyr Met Asn Tyr Thr Ile Asn Thr Thr Lys Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Tyr Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Arg Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Tyr Asn Ser Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Ile Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Arg Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Ala Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser
565 570
<210> 54
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 54
Met Glu Leu Leu Ile His Arg Ser Ser Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Ile Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Val Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln Tyr Met Asn Tyr Thr Ile Asn Thr Thr Lys Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Tyr Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Gln Leu Leu Pro Ile Val Asn
195 200 205
Gln Gln Ser Cys Arg Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Tyr Asn Ser Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Tyr Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Ile Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Arg Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Ala Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Lys
565 570
<210> 55
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 55
Met Glu Leu Leu Ile His Arg Ser Ser Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Val Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Phe Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln Tyr Met Asn Tyr Thr Ile Asn Thr Thr Lys Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Met Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Tyr Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Arg Leu Leu Pro Ile Val Asn
195 200 205
Gln Gln Ser Cys Arg Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Tyr Asn Ser Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Ile Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Ile Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Arg Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Lys
565 570
<210> 56
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 56
Met Glu Leu Leu Ile His Arg Ser Ser Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Ile Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Phe Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln Tyr Met Asn Tyr Thr Ile Asn Thr Thr Lys Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Tyr Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Gln Leu Leu Pro Ile Val Asn
195 200 205
Gln Gln Ser Cys Arg Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Tyr Asn Ser Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Ile Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Ile Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Arg Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Ala Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Lys
565 570
<210> 57
<211> 573
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 57
Met Glu Leu Leu Ile His Arg Ser Ser Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Ile Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Phe Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln Tyr Met Asn Tyr Thr Ile Asn Thr Thr Lys Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Tyr Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Arg Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Tyr Asn Ser Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Ile Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Arg Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Ala Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser
565 570
<210> 58
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 58
Met Glu Leu Leu Ile His Arg Ser Ser Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Ile Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Val Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln Tyr Met Asn Tyr Thr Ile Asn Thr Thr Lys Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Tyr Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Gln Leu Leu Pro Ile Val Asn
195 200 205
Gln Gln Ser Cys Arg Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Tyr Asn Ser Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Tyr Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Ile Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Arg Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Ala Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Lys
565 570
<210> 59
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 59
Met Glu Leu Leu Ile His Arg Ser Ser Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Val Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Phe Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln Tyr Met Asn Tyr Thr Ile Asn Thr Thr Lys Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Met Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Tyr Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Arg Leu Leu Pro Ile Val Asn
195 200 205
Gln Gln Ser Cys Arg Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Tyr Asn Ser Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Ile Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Ile Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Arg Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Lys
565 570
<210> 60
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 60
Met Glu Leu Leu Ile His Arg Ser Ser Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Ile Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Phe Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Thr Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln His Met Asn Tyr Thr Ile Asn Thr Thr Lys Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Tyr Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Gln Leu Leu Pro Ile Val Asn
195 200 205
Gln Gln Ser Cys Arg Ile Phe Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Tyr Asn Ser Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Ile Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Ile Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Lys
565 570
<210> 61
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 61
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Pro Thr Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Val Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Tyr Ser Val Leu Thr Phe Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Leu Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Tyr Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Ile Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Met Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Ala Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Ile Leu Leu Ser Leu Ile Ala Val
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Arg Ser Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Asn
565 570
<210> 62
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 62
Met Glu Leu Pro Ile Leu Lys Thr Asn Ala Ile Thr Thr Ile Leu Ala
1 5 10 15
Ala Val Thr Leu Cys Phe Ala Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Ala Asn Ser Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Thr Lys Asn Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Tyr Ser Val Leu Thr Phe Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Leu Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Tyr Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Ile
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Ala Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Ile Leu Leu Ala Leu Ile Ala Val
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Arg Ser Thr Pro Val Ile Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Asn
565 570
<210> 63
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 63
Met Glu Leu Pro Ile Leu Lys Thr Asn Ala Ile Thr Thr Ile Leu Ala
1 5 10 15
Ala Val Thr Leu Cys Phe Ala Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Thr Lys Asn Thr Asn Val Thr
115 120 125
Val Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Tyr Ser Val Leu Thr Phe Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Leu Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Tyr Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Ile
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Ala Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Ile Leu Leu Ser Leu Ile Ala Val
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Arg Ser Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Asn
565 570
<210> 64
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 64
Met Glu Leu Pro Ile Leu Lys Thr Asn Ala Ile Thr Thr Ile Leu Ala
1 5 10 15
Ala Val Thr Leu Cys Phe Ala Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Thr Lys Thr Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Tyr Ser Val Leu Thr Phe Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Leu Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Tyr Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Ala Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Ile Leu Leu Ser Leu Ile Ala Val
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Arg Ser Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Ser
565 570
<210> 65
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 65
Met Glu Leu Pro Ile Leu Lys Thr Asn Ala Ile Thr Thr Ile Leu Ala
1 5 10 15
Ala Val Thr Leu Cys Phe Ala Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Gln Ala Ala Asn Ser Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Thr Lys Asn Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Tyr Ser Val Leu Thr Phe Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Leu Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Tyr Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Ile
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Ala Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Ile Leu Leu Ser Leu Ile Ala Val
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Arg Ser Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Asn
565 570
<210> 66
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 66
Met Glu Leu Leu Val His Arg Ser Ser Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Ile Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Phe Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln Tyr Met Asn Tyr Thr Ile Asn Thr Thr Asn Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Tyr Ser Val Leu Thr Phe Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Gln Leu Leu Pro Ile Leu Asn
195 200 205
Gln Gln Ser Cys Arg Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Tyr Asn Ser Arg Leu Leu Glu Ile Ala Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Ile Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Ile Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Arg Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Ala Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Lys
565 570
<210> 67
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 67
Met Glu Leu Pro Ile Leu Lys Thr Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Thr Lys Asn Asn Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Tyr Ser Val Leu Thr Phe Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Leu Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Tyr Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Val Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Ile Leu Leu Leu Leu Ile Ala Val
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Arg Ser Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Asn
565 570
<210> 68
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 68
Met Glu Leu Pro Ile Leu Lys Thr Asn Ala Ile Thr Thr Ile Phe Ala
1 5 10 15
Ala Val Thr Leu Cys Phe Ala Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Thr Lys Asn Asn Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Tyr Ser Val Leu Thr Phe Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Leu Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Tyr Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Ile
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Val Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Ile Leu Leu Leu Leu Ile Ala Val
530 535 540
Gly Leu Phe Leu Tyr Cys Lys Ala Arg Ser Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Glu Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Asn
565 570
<210> 69
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 69
Met Glu Leu Pro Ile Leu Lys Thr Asn Ala Ile Thr Thr Ile Phe Ala
1 5 10 15
Ala Val Thr Leu Cys Phe Ala Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Val Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Thr Lys Asn Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Tyr Ser Val Leu Thr Phe Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Leu Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Tyr Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Ile
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Ala Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Ile Leu Leu Ser Leu Ile Ala Val
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Arg Ser Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Asn
565 570
<210> 70
<211> 568
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 70
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Val Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Tyr Ser Val Leu Thr Phe Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Leu Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Tyr Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu Ser Ala Ile Gly Gly Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln
515 520 525
Ala Tyr Val Arg Lys Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu
530 535 540
Gly Gly Leu Val Pro Arg Gly Ser His His His His His His Ser Ala
545 550 555 560
Trp Ser His Pro Gln Phe Glu Lys
565
<210> 71
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 71
Met Glu Leu Leu Ile His Arg Ser Ser Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Val Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Phe Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln Tyr Met Asn Tyr Thr Ile Asn Thr Thr Lys Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Tyr Ser Val Leu Thr Phe Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Arg Leu Leu Pro Ile Leu Asn
195 200 205
Gln Gln Ser Cys Arg Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Tyr Asn Ser Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Ile Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Ile Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Arg Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Lys
565 570
<210> 72
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 72
Met Glu Leu Leu Ile His Arg Ser Ser Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Ile Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Phe Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln Tyr Met Asn Tyr Thr Ile Asn Thr Thr Lys Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Tyr Ser Val Leu Thr Phe Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Gln Leu Leu Pro Ile Leu Asn
195 200 205
Gln Gln Ser Cys Arg Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Tyr Asn Ser Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Ile Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Ile Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Arg Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Ala Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Lys
565 570
<210> 73
<211> 573
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 73
Met Glu Leu Leu Ile His Arg Ser Ser Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Ile Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Phe Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln Tyr Met Asn Tyr Thr Ile Asn Thr Thr Lys Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Tyr Ser Val Leu Thr Phe Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Gln Leu Leu Pro Ile Leu Asn
195 200 205
Lys Gln Ser Cys Arg Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Tyr Asn Ser Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Ile Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Arg Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Ala Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser
565 570
<210> 74
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 74
Met Glu Leu Leu Ile His Arg Ser Ser Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Ile Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Val Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln Tyr Met Asn Tyr Thr Ile Asn Thr Thr Lys Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Tyr Ser Val Leu Thr Phe Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Gln Leu Leu Pro Ile Leu Asn
195 200 205
Gln Gln Ser Cys Arg Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Tyr Asn Ser Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Tyr Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Ile Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Arg Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Ala Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Lys
565 570
<210> 75
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 75
Met Glu Leu Leu Ile His Arg Ser Ser Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Val Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Phe Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln Tyr Met Asn Tyr Thr Ile Asn Thr Thr Lys Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Met Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Tyr Ser Val Leu Thr Phe Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Arg Leu Leu Pro Ile Leu Asn
195 200 205
Gln Gln Ser Cys Arg Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Tyr Asn Ser Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Ile Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Ile Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Arg Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Lys
565 570
<210> 76
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 76
Met Glu Leu Leu Ile His Arg Ser Ser Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Ile Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Phe Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln Tyr Met Asn Tyr Thr Ile Asn Thr Thr Lys Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Tyr Ser Val Leu Thr Phe Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Gln Leu Leu Pro Ile Leu Asn
195 200 205
Gln Gln Ser Cys Arg Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Tyr Asn Ser Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Ile Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Ile Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Arg Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Ala Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Lys
565 570
<210> 77
<211> 573
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 77
Met Glu Leu Leu Ile His Arg Ser Ser Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Ile Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Phe Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln Tyr Met Asn Tyr Thr Ile Asn Thr Thr Lys Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Tyr Ser Val Leu Thr Phe Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Gln Leu Leu Pro Ile Leu Asn
195 200 205
Lys Gln Ser Cys Arg Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Tyr Asn Ser Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Ile Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Arg Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Ala Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser
565 570
<210> 78
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 78
Met Glu Leu Leu Ile His Arg Ser Ser Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Ile Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Val Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln Tyr Met Asn Tyr Thr Ile Asn Thr Thr Lys Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Tyr Ser Val Leu Thr Phe Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Gln Leu Leu Pro Ile Leu Asn
195 200 205
Gln Gln Ser Cys Arg Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Tyr Asn Ser Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Tyr Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Ile Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Arg Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Ala Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Lys
565 570
<210> 79
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 79
Met Glu Leu Leu Ile His Arg Ser Ser Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Val Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Phe Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln Tyr Met Asn Tyr Thr Ile Asn Thr Thr Lys Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Met Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Tyr Ser Val Leu Thr Phe Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Arg Leu Leu Pro Ile Leu Asn
195 200 205
Gln Gln Ser Cys Arg Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Tyr Asn Ser Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Ile Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Ile Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Arg Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Lys
565 570
<210> 80
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 80
Met Glu Leu Leu Ile His Arg Ser Ser Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Ile Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Phe Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Thr Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln His Met Asn Tyr Thr Ile Asn Thr Thr Lys Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Tyr Ser Val Leu Thr Phe Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Gln Leu Leu Pro Ile Leu Asn
195 200 205
Gln Gln Ser Cys Arg Ile Phe Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Tyr Asn Ser Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Ile Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Ile Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Lys
565 570
<210> 81
<211> 568
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 81
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Val Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Tyr Ser Val Leu Thr Phe Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Leu Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Tyr Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Tyr Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Val
500 505 510
Val Ser Ala Ile Gly Gly Phe Ile Pro Glu Ala Pro Arg Asp Gly Gln
515 520 525
Ala Tyr Val Arg Lys Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu
530 535 540
Gly Gly Leu Val Pro Arg Gly Ser His His His His His His Ser Ala
545 550 555 560
Trp Ser His Pro Gln Phe Glu Lys
565
<210> 82
<211> 568
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 82
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Val Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu Ser Ala Ile Gly Gly Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln
515 520 525
Ala Tyr Val Arg Lys Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu
530 535 540
Gly Gly Leu Val Pro Arg Gly Ser His His His His His His Ser Ala
545 550 555 560
Trp Ser His Pro Gln Phe Glu Lys
565
<210> 83
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 83
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Val Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Lys
565 570
<210> 84
<211> 568
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 84
Met Glu Leu Leu Ile His Arg Ser Ser Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Ile Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Phe Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Thr Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln His Met Asn Tyr Thr Ile Asn Thr Thr Lys Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Gln Leu Leu Pro Ile Val Asn
195 200 205
Gln Gln Ser Cys Arg Ile Phe Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Ser Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Ile Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Ile Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu Ser Ala Ile Gly Gly Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln
515 520 525
Ala Tyr Val Arg Lys Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu
530 535 540
Gly Gly Leu Val Pro Arg Gly Ser His His His His His His Ser Ala
545 550 555 560
Trp Ser His Pro Gln Phe Glu Lys
565
<210> 85
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 85
Met Glu Leu Leu Ile His Arg Ser Ser Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Ile Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Phe Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Thr Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln His Met Asn Tyr Thr Ile Asn Thr Thr Lys Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Gln Leu Leu Pro Ile Val Asn
195 200 205
Gln Gln Ser Cys Arg Ile Phe Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Ser Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Ile Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Ile Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Lys
565 570
<210> 86
<211> 568
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 86
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Val Ala Val Cys Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Phe Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Leu Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Cys Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu Ser Ala Ile Gly Gly Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln
515 520 525
Ala Tyr Val Arg Lys Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu
530 535 540
Gly Gly Leu Val Pro Arg Gly Ser His His His His His His Ser Ala
545 550 555 560
Trp Ser His Pro Gln Phe Glu Lys
565
<210> 87
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 87
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Val Ala Val Cys Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Phe Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Leu Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Cys Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Lys
565 570
<210> 88
<211> 568
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 88
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Val Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Phe Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Leu Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu Ser Ala Ile Gly Gly Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln
515 520 525
Ala Tyr Val Arg Lys Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu
530 535 540
Gly Gly Leu Val Pro Arg Gly Ser His His His His His His Ser Ala
545 550 555 560
Trp Ser His Pro Gln Phe Glu Lys
565
<210> 89
<211> 574
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 89
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Val Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Phe Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Leu Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Lys
565 570
<210> 90
<211> 568
<212> PRT
<213> 呼吸道合胞病毒（Respiratory syncytial virus）
<400> 90
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Val Ala Val Cys Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Cys Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
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Ala Tyr Val Arg Lys Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu
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Gly Gly Leu Val Pro Arg Gly Ser His His His His His His Ser Ala
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Trp Ser His Pro Gln Phe Glu Lys
565
<210> 91
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<213> 呼吸道合胞病毒（Respiratory syncytial virus）
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Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
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Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
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Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
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65 70 75 80
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Met Gln Ser Thr Pro Ala Thr Asn Asn Arg Ala Arg Arg Glu Leu Pro
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Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
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Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
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Gly Ser Ala Ile Ala Ser Gly Val Ala Val Cys Lys Val Leu His Leu
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Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
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Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
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Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
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Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
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Met Cys Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
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Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
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Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
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Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
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Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
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Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Val
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Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
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Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
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Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
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Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
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Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
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Thr Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
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Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
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Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Lys
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<210> 92
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<213> 人工序列
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<223> 人工序列的描述:合成
多肽
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Ser Ala Ile Gly Gly Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln Ala
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Tyr Val Arg Lys Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu Gly
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Ser His Pro Gln Phe Glu Lys
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<213> 人工序列
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<223> 人工序列的描述:合成多肽
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Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu
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<223> 人工序列的描述:合成多肽
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Leu Val Pro Arg Gly Ser
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<213> 人工序列
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<223> 人工序列的描述:合成6xHis标签
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His His His His His His
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<213> 人工序列
<220>
<223> 人工序列的描述:合成多肽
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Trp Ser His Pro Gln Phe Glu Lys
1 5

Claims (65)

1.一种突变RSV F分子，包含在第428位氨基酸残基处，或在通过与SEQ ID NO.1比对确定的对应于第428位残基的氨基酸处，突变为酪氨酸的点突变。
2.根据权利要求1所述的突变RSV F分子，进一步包含在第185位氨基酸残基处，或在通过与SEQ ID NO.1比对确定的对应于第185位残基的氨基酸处，突变为酪氨酸的点突变。
3.根据权利要求1所述的突变RSV F分子，进一步包含在第226位氨基酸残基处，或在通过与SEQ ID NO.1比对确定的对应于第226位残基的氨基酸处，突变为酪氨酸的点突变。
4.根据权利要求1所述的突变RSV F分子，进一步包含：(a)在第185位氨基酸残基处，或在通过与SEQ ID NO.1比对确定的对应于第185位残基的氨基酸处，突变为酪氨酸的点突变；和，(b)在第226位氨基酸残基处，或在通过与SEQ ID NO.1比对确定的对应于第226位残基的氨基酸处，突变为酪氨酸的点突变。
5.根据权利要求1至4中任一项所述的突变RSV F分子，包含跨膜结构域和胞质结构域。
6.根据权利要求1至4中任一项所述的突变RSV F分子，其中所述分子不包含跨膜结构域或胞质结构域。
7.根据前述权利要求中任一项所述的突变RSV F分子，其中所述分子是RSV A型或RSVB型分子。
8.根据前述权利要求中任一项所述的突变RSV F分子，其中所述分子与预融合特异性抗体结合。
9.根据前述权利要求中任一项所述的突变RSV F分子，其中所述分子与识别抗原位点
Figure FDA0002444986390000011
的抗体结合。
10.根据前述权利要求中任一项所述的突变RSV F分子，其中所述分子与，选自由D25、5C4、AM22和AM14组成的组中的抗体结合。
11.根据前述权利要求中任一项所述的突变RSV F分子，其中所述分子包含F2多肽和F1多肽，其中该F2多肽的C-末端与该F1多肽的N-末端通过二硫键连接。
12.根据前述权利要求中任一项所述的突变RSV F分子，其中所述分子包含F2多肽和F1多肽，其中该F2多肽的C-末端与该F1多肽的N-末端通过人工引入的肽接头连接。
13.根据前述权利要求中任一项所述的突变RSV F分子，包含：约84个氨基酸残基的F2多肽；和，约375个氨基酸残基的F1多肽。
14.根据前述权利要求中任一项所述的突变RSV F分子，包含：约74～84个氨基酸残基的F2多肽；和，约365～375个氨基酸残基的F1多肽。
15.根据前述权利要求中任一项所述的突变RSV F分子，包含：
(a)F2多肽，该F2多肽包含SEQ ID NOs 21～81中任一个的第26～109位氨基酸残基，或由SEQ ID NOs 21～81中任一个的第26～109位氨基酸残基组成；和，
(b)F1多肽，该F1多肽包含SEQ ID NOs 21～81中任一个的第137～513位氨基酸残基，或由SEQ ID NOs 21～81中任一个的第137～513位氨基酸残基组成。
16.根据前述权利要求中任一项所述的突变RSV F分子，包含：
(a)F2多肽，该F2多肽包含SEQ ID NOs 21～81中任一个的第26～109位氨基酸残基中的约74～84个氨基酸，或由SEQ ID NOs 21～81中任一个的第26～109位氨基酸残基中的约74～84个氨基酸组成；和，
(b)F1多肽，该F1多肽包含SEQ ID NOs 21～81中任一个的第137～513位氨基酸残基中的约365～375个氨基酸，或由SEQ ID NOs 21～81中任一个的第137～513位氨基酸残基中约365～375个氨基酸组成。
17.根据前述权利要求中任一项所述的突变RSV F分子，包含：
(a)F2多肽，该F2多肽包含SEQ ID NO 81的第26～109位氨基酸残基，或由SEQ ID NO81的第26～109位氨基酸残基组成；和，
(b)F1多肽，该F1多肽包含SEQ ID NO.81的第137～513位氨基酸残基，或由SEQ IDNO.81的第137～513位氨基酸残基组成。
18.根据前述权利要求中任一项所述的突变RSV F分子，包含：
(a)F2多肽，该F2多肽包含SEQ ID NO 81的第26～109位氨基酸残基中的约74～84个氨基酸，或由SEQ ID NO 81的第26～109位氨基酸残基中的约74～84个氨基酸组成；和，
(b)F1多肽，该F1多肽包含SEQ ID NO.81的第137～513位氨基酸残基中的约365～375个氨基酸，或由SEQ ID NO.81的第137～513位氨基酸残基中的约365～375个氨基酸组成。
19.根据前述权利要求中任一项所述的突变RSV F分子，其中所述分子通过一个或多个二酪氨酸交联，稳定处于预融合构象。
20.根据前述权利要求中任一项所述的突变RSV F分子，其中所述分子为成熟的RSV F三聚体。
21.根据前述权利要求中任一项所述的突变RSV F分子，其中所述分子是通过三个或更多个二酪氨酸交联，稳定处于预融合构象的成熟的RSV F三聚体。
22.根据前述权利要求中任一项所述的突变RSV F分子，其中所述分子包含在以下酪氨酸之间的二酪氨酸交联：(a)在第428位氨基酸残基处，或通过与SEQ ID NO.1比对确定的与其对应的氨基酸残基处的酪氨酸，和(b)在第185位氨基酸残基处，或通过与SEQ ID NO.1比对确定的与其对应的氨基酸残基处的酪氨酸。
23.根据前述权利要求中任一项所述的突变RSV F分子，其中所述分子包含在以下酪氨酸之间的二酪氨酸交联：(a)在第198位氨基酸残基处，或通过与SEQ ID NO.1比对确定的对应的氨基酸残基处的酪氨酸；和，(b)在第226位氨基酸残基处，或通过与SEQ ID NO.1比对确定的与其对应的氨基酸残基处的酪氨酸。
24.根据前述权利要求中任一项所述的突变RSV F分子，其中所述分子包含以下两种二酪氨酸交联：(i)在第198位氨基酸残基处的酪氨酸和第226位氨基酸残基处的酪氨酸之间，或通过与SEQ ID NO.1比对确定的与其各自对应的氨基酸残基处的酪氨酸之间的二酪氨酸交联；和，(ii)在第428位氨基酸残基处的酪氨酸和第185位氨基酸残基处的酪氨酸之间，或通过与SEQ ID NO.1比对确定的与其各自对应的氨基酸残基处的酪氨酸之间的二酪氨酸交联。
25.根据前述权利要求中任一项所述的突变RSV F分子，其中所述分子为包含三个二酪氨酸交联的成熟的RSV F三聚体，其中每个二酪氨酸交联位于以下酪氨酸之间：
(a)在第428位氨基酸残基处，或通过与SEQ ID NO.1比对确定的与其对应的氨基酸残基处的酪氨酸；和，
(b)在第185位氨基酸残基处，或通过与SEQ ID NO.1比对确定的与其对应的氨基酸残基处的酪氨酸。
26.根据前述权利要求中任一项所述的突变RSV F分子，其中所述分子为包含三个二酪氨酸交联的成熟的RSV F三聚体，其中每个二酪氨酸交联位于以下酪氨酸之间：
(a)在第198位氨基酸残基处，或通过与SEQ ID NO.1比对确定的与其对应的氨基酸残基处的酪氨酸；和，
(b)在第226位氨基酸残基处，或通过与SEQ ID NO.1比对确定的与其对应的氨基酸残基处的酪氨酸。
27.根据前述权利要求中任一项所述的突变RSV F分子，其中所述分子为六个二酪氨酸交联的成熟的RSV F三聚体，在所述六个二酪氨酸交联中，
(i)三个在第198位氨基酸残基处的酪氨酸和第226位氨基酸残基处的酪氨酸之间，或在通过与SEQ ID NO.1比对确定的与其各自对应的氨基酸残基处的酪氨酸之间；和，
(ii)三个在第428位氨基酸残基处的酪氨酸和在第185位氨基酸残基处的酪氨酸之间，或在通过与SEQ ID NO.1比对确定的其各自对应氨基酸残基处的酪氨酸之间。
28.根据前述权利要求中任一项所述的突变RSV F分子，其中所述分子进一步包含一个或多个人工引入的非DT交联。
29.根据前述权利要求中任一项所述的突变RSV F分子，其中所述分子进一步包含一个或多个人工引入的二硫键。
30.根据前述权利要求中任一项所述的突变RSV F分子，其中所述分子进一步包含一个或多个突变为半胱氨酸的点突变。
31.根据权利要求29所述的突变RSV F分子，其中所述二硫键在两个半胱氨酸之间形成，该两个半胱氨酸中的一个或两个是通过点突变引入的。
32.根据前述权利要求中任一项所述的突变RSV F分子，其中所述分子包含，在第155位氨基酸残基处，或通过与SEQ ID NO.1比对确定的与其对应的氨基酸残基处，突变为半胱氨酸的点突变。
33.根据前述权利要求中任一项所述的突变RSV F分子，其中所述分子包含，在第290位氨基酸残基处，或通过与SEQ ID NO.1比对确定的与其对应的氨基酸残基处，突变为半胱氨酸的点突变。
34.根据前述权利要求中任一项所述的突变RSV F分子，其中所述分子包含以下两种点突变：
(a)在第155位氨基酸残基处，或在通过与SEQ ID NO.1比对确定的与其对应的氨基酸残基处，突变为半胱氨酸的点突变；和，
(b)在第290位氨基酸残基处，或在通过与SEQ ID NO.1比对确定的与其对应的氨基酸残基处，突变为半胱氨酸的点突变。
35.根据前述权利要求中任一项所述的突变RSV F分子，其中所述分子包含一个或多个人工引入的空腔填充突变。
36.根据权利要求35所述的突变RSV F分子，其中所述分子包含，在第190位氨基酸残基处，或在通过与SEQ ID NO.1比对确定的与其对应的氨基酸残基处，突变为苯丙氨酸的点突变。
37.根据权利要求35所述的突变RSV F分子，其中所述分子包含，在第207位氨基酸残基处，或在通过与SEQ ID NO.1比对确定的与其对应的氨基酸残基处，突变为亮氨酸的点突变。
38.根据权利要求35所述的突变RSV F分子，其中所述分子包含以下两种突变：
(a)在第190位氨基酸残基处，或在通过与SEQ ID NO.1比对确定的与其对应的氨基酸残基处，突变为苯丙氨酸的突变；和，
(b)在第207位氨基酸残基处，或在通过与SEQ ID NO.1比对确定的与其对应的氨基酸残基处，突变为亮氨酸的点突变。
39.根据权利要求35所述的突变RSV F分子，其中所述分子包含一个或多个空腔填充突变，所述空腔填充突变选自由58W、83W、87F、90L、153W、190F、203W、207L、220L、260W、296F和298L组成的组。
40.根据前述权利要求中任一项所述的突变RSV F分子，其中所述分子包含异源低聚化结构域。
41.根据权利要求40所述的突变RSV F分子，其中所述异源低聚化结构域为三聚化结构域。
42.根据权利要求41所述的突变RSV F分子，其中所述三聚化结构域为折叠子结构域、GCN4结构域或T4纤维蛋白结构域。
43.根据权利要求41所述的突变RSV F分子，其中所述三聚化结构域为折叠子结构域，包含SEQ ID NO.93。
44.根据前述权利要求中任一项所述的突变RSV F分子，其中所述分子包含一个或多个用于检测RSV F分子的标签。
45.根据前述权利要求中任一项所述的突变RSV F分子，其中所述分子包含一个或多个用于纯化RSV F分子的标签。
46.根据权利要求44或45中所述的突变RSV F分子，其中所述标签选自由Strep标签、Strep II标签、FLAG标签、谷胱甘肽S-转移酶(GST)标签、绿色荧光蛋白(GFP)标签、血凝素A(HA)标签、组氨酸(His)标签、荧光素酶标签、麦芽糖结合蛋白(MBP)标签、c-Myc标签、蛋白A标签和蛋白G标签组成的组。
47.根据权利要求44或45中所述的突变RSV F分子，其中所述标签包含SEQ ID NO.95。
48.根据权利要求44或45中所述的突变RSV F分子，其中所述标签包含SEQ ID NO.96。
49.根据权利要求44至48中任一项所述的突变RSV F分子，其中所述标签为可经蛋白酶解切割的标签。
50.一种突变RSV F分子，包含在以下每一氨基酸残基处，突变为酪氨酸的点突变：(a)在第428位氨基酸残基处，(b)在第226位氨基酸残基处，和(c)在第185位氨基酸残基处，或通过与SEQ ID NO.1比对确定的与其各自对应的氨基酸处。
51.根据权利要求50所述的突变RSV F分子，包含SEQ ID No.81的第26～109位和第137～513位氨基酸残基。
52.一种突变RSV F分子，包含：
(i)在以下每一氨基酸残基处，突变为酪氨酸的点突变：(a)在第428位氨基酸残基处，(b)在第226位氨基酸残基处，和(c)在第185位氨基酸残基处，或在通过与SEQ ID NO.1比对确定的与其各自对应的氨基酸处；
(ii)在第190位氨基酸残基处，或在通过与SEQ ID NO.1比对确定的与其对应的氨基酸残基处，突变为苯丙氨酸的点突变，和
(iii)在第207位氨基酸残基处，或在通过与SEQ ID NO.1比对确定的与其对应的氨基酸残基处，突变为亮氨酸的点突变。
53.根据权利要求52所述的突变RSV F分子，包含SEQ ID No.81的第26～109位和第137～513位氨基酸残基。
54.一种可溶性成熟的三聚体RSVF分子，包含在以下每一氨基酸残基处，突变为酪氨酸的点突变：(a)在第428位氨基酸残基处，(b)在第226位氨基酸残基处，和(c)在第185位氨基酸残基处，或在通过与SEQ ID NO.1比对确定的与其各自对应的氨基酸处。
55.根据权利要求54所述的可溶性成熟的三聚体RSVF分子，包含SEQ ID No.81的第26～109位和第137～513位氨基酸残基。
56.一种可溶性成熟的三聚体RSVF分子，包含：
(i)在以下每一氨基酸残基处，突变为酪氨酸的点突变：(a)在第428位氨基酸残基处，(b)在第226位氨基酸残基处，和(c)在第185位氨基酸残基处，或在通过与SEQ ID NO.1比对确定的与其各自对应的氨基酸处；
(ii)在第190位氨基酸残基处，或在通过与SEQ ID NO.1比对确定的其对应的氨基酸残基处，突变为苯丙氨酸的点突变；和
(iii)在第207位氨基酸残基处，或在通过与SEQ ID NO.1比对确定的与其对应的氨基酸残基处，突变为亮氨酸的点突变。
57.根据权利要求56所述的可溶性成熟的三聚体RSVF分子，包含SEQ ID No.81的第26～109位和第137～513位氨基酸残基。
58.根据权利要求50至57中任一项所述的RSVF分子，其中所述分子包含一个或多个DT交联，并稳定处于预F构象。
59.一种核酸，编码根据前述权利要求中任一项所述的突变RSV F分子。
60.一种载体，包含根据权利要求59所述的核酸。
61.一种细胞，包含权利要求59所述的核酸分子。
62.一种细胞，包含权利要求60所述的载体。
63.一种药物组合物，包含根据权利要求1至58中任一项所述的突变RSV F分子。
64.根据权利要求63所述的药物组合物，进一步包含佐剂。
65.一种接种抗RSV的疫苗的方法，所述方法包括对有需要的受试者施用有效量的权利要求64所述的药物组合物。
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