CN114276422B - 新型冠状病毒s蛋白多肽抗原及其应用 - Google Patents
新型冠状病毒s蛋白多肽抗原及其应用 Download PDFInfo
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Abstract
本发明提供一种新型冠状病毒S蛋白多肽抗原及其应用。本发明提供的新型冠状病毒S蛋白多肽抗原的氨基酸序列如SEQ ID NO：1‑110任一所示。本发明的多肽能刺激产生S蛋白的结合抗体，也能刺激产生S蛋白RBD结构域的结合抗体，抗体结合效价达到104以上。同时，本发明的多肽刺激产生的兔免疫血清对ACE2‑RBD的结合有一定的阻断作用。本发明的多肽能够被用来制备抗原、抗体、试剂盒等相关检测试剂以及多肽疫苗、核酸疫苗、蛋白重组疫苗等相关疫苗产品，从而为防控此类病毒的传染和流行提供更有力的工具。
Description
技术领域
本发明属于分子免疫学领域，具体地说，涉及新型冠状病毒S蛋白多肽抗原及其应用。
背景技术
由新型冠状病毒“SARS-CoV-2”(Severe Acute Respiratory SyndromeCoronavirus 2)感染所致的新型冠状病毒肺炎(Corona Virus Disease 2019,COVID-19)尚未发现特效药，故以预防感染为目的的新冠特异性疫苗成为降低感染率、抑制疫情恶化的希望。
疫苗包括灭活疫苗、减毒疫苗、亚单位疫苗(蛋白疫苗、多肽疫苗)、核酸疫苗 (DNA疫苗、RNA疫苗)。多肽疫苗是按照病原体抗原基因中已知或预测的某段抗原表位的氨基酸序列，通过化学合成技术制备的疫苗。由于完全是合成的，不存在毒力回 升或灭活不全的问题，特别适合一些还不能通过体外培养方式获得足够量的抗原的微生 物病原体。与其它技术路线疫苗相比，病毒抗原表位多肽疫苗具有以下优势：更适用于 应对病毒的变异；能达到快速、高效生产的要求，降低疫苗制作的成本；疫苗中无完整 的病毒结构，安全性较高；可将不同抗原得到的各种多肽结合在一种载体中；能够针对 复杂的非连续性天然抗原决定簇，构建相应的合成抗原多肽。
尽管多肽疫苗有较多的优势，但是同样也存在一些技术瓶颈问题，其中最主要的问 题就是多肽分子量小，免疫原性低、免疫应答效果较差。并非所有多肽片段都可激发机体免疫反应，通过免疫原的选择和设计达到正确有效地激发人体保护性免疫反应，是多 肽疫苗开发首要的关键环节。
发明内容
本发明的主要目的在于提供一种新型冠状病毒S蛋白多肽抗原、多肽疫苗及其应用。
为了实现上述目的，本发明采用的技术方案如下：
第一方面，提供了一种多肽，该多肽选自表1所示的SEQ ID NO：1至SEQ ID NO：110所示的肽段中的任意一条。
第二方面，提供了一种抗原表位，该抗原表位选自表1所示的SEQ ID NO：1至SEQID NO：110所示的肽段中的任意一条或多条。
表1：
进一步地，抗原表位包括SEQ ID NO：1至SEQ ID NO：15中的任意一条或多条。
第三方面，提供了一种多肽-载体蛋白偶联物，该多肽-载体蛋白偶联物包括第一方 面所述的多肽以及与多肽偶联的载体蛋白。
进一步地，所述多肽包括SEQ ID NO：1至SEQ ID NO：15中的任意一条或多条。
进一步地，载体蛋白选自牛血清蛋白、卵清白蛋白、钥孔血蓝蛋白或酪蛋白；
优选地，多肽通过连接序列与载体蛋白偶联，更优选地，每个载体蛋白偶联5～50条多肽，进一步优选5～30条多肽。
第四方面，提供了一种抗原，该抗原包括一种或多种第三方面所述的任一种多肽-载体蛋白偶联物。
第五方面，提供了一种冠状病毒抗体检测试剂盒，该试剂盒包括第一方面所述的多 肽、第二方面所述的抗原表位或第四方面所述的任一种抗原。
进一步地，抗原为预包被抗原；优选地，预包被抗原包被于固相载体上；优选地，固相载体包括酶标板、膜载体或微球；优选地，膜载体包括硝酸纤维素膜、玻璃纤维素 膜或尼龙膜；优选地，膜载体上还包被有阳性对照物，多肽和阳性对照物按检测顺序在膜载体上依次设置。
进一步地，试剂盒还包括如下至少之一：(1)酶标二抗，更优选酶标二抗为HRP 标记的二抗；(2)胶体金结合垫，胶体金结合垫上包被有胶体金标记的多肽和阳性对 照物的特异性结合物；(3)标记垫，标记垫上包被有荧光标记的微球，微球上负载有 阳性对照物的特异性结合物；优选地，阳性对照物选自鼠免疫球蛋白、人免疫球蛋白、 羊免疫球蛋白或兔免疫球蛋白，相应地，阳性对照物的特异性结合物选自抗鼠免疫球蛋 白、抗人免疫球蛋白、抗羊免疫球蛋白或抗兔免疫球蛋白。
第六方面，提供了第一方面所述的任一种多肽或第二方面所述的任一种抗原表位在 制备治疗冠状病毒引起的疾病的药物中的应用。
进一步地，冠状病毒为SARS-CoV-2。
进一步地，药物为抗体或疫苗；优选地，疫苗为多肽疫苗或基因疫苗。
第七方面，提供了一种药物，该药物为抗体或疫苗，抗体通过第四方面所述的任一种抗原免疫动物得到；疫苗为多肽疫苗或基因疫苗，其中，多肽疫苗包含第一方面所述 的任一种多肽；基因疫苗包含编码第一方面所述的任一种多肽的核酸。
进一步地，抗体为中和抗体；优选地，多肽选自SEQ ID NO：1至SEQ ID NO：15 中的任意一种或多种；更优选，多肽选自SEQ ID NO：5、SEQ ID NO：6、SEQ ID NO：8、SEQ ID NO：11、SEQ ID NO：13及SEQ ID NO：14中的任意一条或多条。
第八方面，提供了一种多肽组合物，该多肽组合物包括SEQ ID NO：1至SEQ ID NO：110所示的肽段中的至少两条。
进一步地，多肽组合物中至少包括SEQ ID NO：1至SEQ ID NO：15所示的肽段中 的任意一条；优选地，多肽组合物中至少包括SEQ ID NO：5、SEQ ID NO：6、SEQ ID NO：8、SEQID NO：11、SEQ ID NO：13及SEQ ID NO：14中的任意一条。
第九方面，提供了一种多肽疫苗，多肽疫苗包括SEQ ID NO：1至SEQ ID NO：110 所示的肽段中的任意一条或多条。
进一步地，多肽至少包括SEQ ID NO：1至SEQ ID NO：15所示的肽段中的任意一条；
优选地，多肽疫苗中至少包括SEQ ID NO：5、SEQ ID NO：6、SEQ ID NO：8、SEQ IDNO：11、SEQ ID NO：13及SEQ ID NO：14中的任意一条。
进一步地，多肽疫苗包括多条肽段，多条肽段以串联形式存在，优选地，多肽疫苗中至少一条肽段串联1～10次，优选1～6次；更优选地，多条肽段经连接臂串联连接； 进一步优选地，连接臂为甘氨酸、赖氨酸、AEA、Ava、ANP、β-丙氨酸、GAB或 PEG。
第十方面，提供了第一方面所述的任一种多肽在制备治疗冠状病毒引起的疾病的疫 苗中的应用。
进一步地，冠状病毒为SARS-CoV-2；优选地，疫苗包括SEQ ID NO：1至SEQ ID NO：15所示的肽段中的任意一条；
优选地，疫苗至少包括SEQ ID NO：5、SEQ ID NO：6、SEQ ID NO：8、SEQ ID NO：11、SEQ ID NO：13及SEQ ID NO：14中所示的肽段中的任意一条；
第十一方面，提供了一种核酸疫苗，该核酸疫苗包括核酸，核酸编码第一方面所述的任一种多肽，或者任一种多肽组合物。
进一步地，核酸疫苗为DNA疫苗或RNA疫苗；优选地，RNA疫苗为mRNA疫苗。
第十二方面，提供了一种重组蛋白疫苗，该重组蛋白疫苗包含SEQID NO：1至SEQID NO：110中任一条或多条肽段。
优选地，重组蛋白疫苗是SEQ ID NO：1至SEQ ID NO：15中任一条或多条肽段；
优选地，重组蛋白疫苗是SEQ ID NO：1至SEQ ID NO：15中任一条或多条肽段与 4～6个组氨酸或4个Gly 1个Ser重组而成的蛋白疫苗；更优选地，重组蛋白疫苗是SEQ IDNO：5、SEQ ID NO：6、SEQ ID NO：8、SEQ ID NO：11、SEQ ID NO：13及SEQ ID NO：14中的任意一条或多条肽段与4～6个组氨酸或4个Gly 1个Ser重组而成的蛋 白疫苗。
本发明的有益效果：
1、本发明的多肽能够被用来制备抗原、抗体、试剂盒等相关检测试剂以及多肽疫苗、核酸疫苗、蛋白重组疫苗等相关疫苗产品，从而为防控此类病毒的传染和流行提供 更有力的工具。
2、本发明的多肽能刺激产生S蛋白的结合抗体，也能刺激产生S蛋白RBD结构域 的结合抗体，抗体结合效价达到104以上。
3、本发明的多肽刺激产生的兔免疫血清对ACE2-RBD的结合有一定的阻断作用。
附图说明
图1.合成多肽抗原片段的纯度检查示例图；
A为氨基酸序列如SEQ ID NO：1所示多肽抗原；B为氨基酸序列如SEQ ID NO： 6所示多肽抗原；C为氨基酸序列如SEQ ID NO：8所示多肽抗原；D为氨基酸序列如SEQ ID NO：13所示多肽抗原；
图2.混合多肽抗原免疫血清抗原竞争结合实验图；
A为RBD蛋白包被检测实施例3获得的兔抗血清竞争性结合ACE2-Fc；B为RBD 蛋白包被检测APN01竞争性结合ACE2-Fc。
具体实施方式
下文将结合具体实施例对本发明的技术方案做更进一步的详细说明。应当理解，下 列实施例仅为示例性地说明和解释本发明，而不应被解释为对本发明保护范围的限制。凡基于本发明上述内容所实现的技术均涵盖在本发明旨在保护的范围内。
除非另有说明，以下实施例中使用的原料和试剂均为市售商品，或者可以通过已知 方法制备。下列实施例中未注明具体条件的实验方法，通常按照常规条件如Sambrook等人，分子克隆：实验室手册(New York:Cold Spring Harbor Laboratory Press,1989)中所述的条件，或按照制造厂商所建议的条件。
定义与说明：
冠状病毒
本文所用的术语“冠状病毒(Coronaviruses)”是单股正链RNA病毒，属于巢病毒目Nidovirales)冠状病毒科(Coronaviridae)正冠状病毒亚科(Orthocoronavirinae)。该病毒可以 感染人、蝙蝠、猪、老鼠、牛、马、山羊、猴子等多种物种。已知感染人的冠状病毒(HCoV)有7种，包括中东呼吸综合征相关冠状病毒(MERSr-CoV)和严重急性呼吸综合征相关冠状病毒(SARSr-CoV)。
在具体的实施方式中，本文所述的冠状病毒是严重急性呼吸道综合征冠状病毒、中 东呼吸综合征冠状病毒或新型冠状病毒。在优选的实施方式中，所述冠状病毒是严重急性呼吸道综合征冠状病毒或SARS-CoV-2；更优选为SARS-CoV-2。
最新分离的冠状病毒为β属新型冠状病毒，WHO命名为SARS-CoV-2，是第7个 可感染人的冠状病毒。新型冠状病毒在复制过程当中，为了不断适应宿主，核苷酸位点 会不断的发生突变，可能会引起一些影响病毒传播力、致病性和免疫原性等特性的变异 株，目前变异新型冠状病毒主要有五种，分别是Alpha、Beta、Gamma、Delta和Lambda。 目前应对新型冠病毒主要是通过防范措施控制病毒扩散，密切监控疫情，对疑似病例进行隔离观察，和注射疫苗。目前冠状病毒尚无特效治疗方法，主要采取对症支持治疗。
新型冠病毒通过表面的S蛋白与人体细胞表面的ACE2受体结合而进入细胞。S蛋白由较长的膜外区、跨膜区和膜内区组成，属于第一类病毒膜融合蛋白(Class I viralfusion protein)。不同冠状病毒的S蛋白最显著的区别在于病毒的组装和释放过程中是否被宿主蛋白酶切割。成熟的S蛋白通常会被宿主蛋白酶(半胱氨酸蛋白酶、胰蛋白酶等) 切割成两个亚基：S1和S2。S1亚基可进一步分成两个相对独立的区域，分别是N-端 区域和C-端区域。S1包含有受体结合域(receptor binding domain，RBD)，大部分的冠状 病毒S蛋白的RBD都位于C-端区域。S2亚基通过跨膜区锚定在膜上，它含有膜融合过 程所需要的基本元件，包括：一个内在的膜融合肽(fusion peptide，FP)，两个7肽重复 序列(heptadrepeat，HR)、一个跨膜临近区(juxamembrain domain，JMD)和一个跨膜结构 域(transmembrane domain，TMD)，以及C末端的胞浆区域(cytoplasmic domain，CD)(约 40个氨基酸长度)。两个HR即HR1和HR2，根据它们的位置又将其称为HR-N和 HR-C，它们之间被大约140个氨基酸形成的中间螺旋结构隔开，当RBD与受体结合后， S2亚基通过将FP插入宿主细胞膜而改变构象，HR1和HR2各形成一个三螺旋结构， 反平行排列集合成六螺旋束(6HB)，共同组成一个融合核心，最终导致病毒膜与细胞膜 融合。因此阻断RBD识别宿主细胞和阻断S2亚基与细胞膜的融合都能够有效抑制病毒 的入侵。
S蛋白因其功能上的重要性而成为一个比较理想的抗原。但是新型冠状病毒是一种 RNA病毒，RNA病毒的疫苗经常会产生副作用，例如ADE(antibody dependentenhancement)。这些副作用往往是疫苗中有一些组分能够刺激产生没有保护作用的免疫反应而引起。
抗原表位：又称抗原决定簇(antigenic determinant)，是抗原物质分子表面或其他部 位具有一定组成和结构的特殊化学基团，能够与相应抗体或致敏淋巴细胞发生特异结合 的结构。在免疫应答过程中，T细胞的抗原受体TCR和B细胞的抗原受体BCR所识别的表位具有不同特点，分别被称为T细胞表位和B细胞表位。T细胞表位一般不位于抗 原分子表面，须由抗原呈递细胞将抗原加工处理为小分子多肽并与MHC分子结合，才 能被TCR识别。T细胞仅能识别经加工处理的表位。而B细胞表位可存在于抗原分子 表面，不须经加工处理，即可直接被B细胞所识别。本申请中指预测的或者筛选的能够 与抗体特异性结合的一条或多条肽段。
多肽：本申请中指预测的或者筛选的能够与抗体或致敏淋巴细胞特异性结合的任意 一条肽段。
多肽-载体蛋白偶联物：本申请中指一条多肽与载体蛋白偶联形成的抗原，其中，一个载体蛋白可以偶联一条或多条多肽，多条多肽偶联时，多条多肽具有相同或不同的 氨基酸序列。根据具体偶联的多肽序列的理化性质的差异、具体载体蛋白的种类的不同 以及偶联方法的不同，每个载体蛋白上所偶联的多肽的条数有所差异，本申请中优选3～ 50条，更优选为3～45条、5～40条、5～35条、5～30条、8～30条、10～30条、12～ 30条、15～30条；或者，更优选为6～36条、8～32条、10～28条、10～26条、10～24 条、10～22条、10～20条、10～18条、10～16条及10～15条中的任意一种情况。
疫苗：通常指具有免疫原性和反应原性两方面的能力，免疫原性指能够刺激机体产 生免疫应答的性能，即刺激机体特定的免疫细胞，使免疫细胞活化、增殖、分化，最终 产生免疫效应物质特异性抗体或致敏淋巴细胞的能力，而反应原性指与其诱导产生的抗 体或致敏淋巴细胞特异性结合的能力。
多肽疫苗：为了提高多肽的免疫原性，以刺激机体产生特异性抗体或致敏性淋巴细 胞，通常会将多肽抗原与佐剂配伍免疫。常用的佐剂包括：氢氧化铝佐剂、短小棒状杆菌、脂多糖、细胞因子或明矾等。弗氏完全佐剂和弗氏不完全佐剂是动物免疫中最常见 的佐剂。
除非另外定义或由背景清楚指示，否则在本公开中的全部技术与科学术语具有如本 公开所属领域的普通技术人员通常理解的相同含义。
实施例1：多肽抗原片段的设计
筛选抗原表位的方法通常是根据目的蛋白序列，利用公开的软件进行生物信息学预 测或根据已有知识进行选择。本发明通过对SARS-CoV-2(EPI_ISL_402124)全基因 组信息中的S蛋白免疫原性分析，二级结构和疏水性预测，可以预测S蛋白的潜在表面 区域，设计了110条多肽，其序列长度和特征见表1。
本发明选取表1中前15条作为后续疫苗肽，具体见下表2。
实施例2.对上述筛选的多肽抗原进行化学合成和免疫原的制备
(1)多肽合成：采用有机化学固相合成法(Fmoc保护的氨基酸，固相载体-树 脂)，采用美国CS公司生产的三通道多肽自动合成仪(CS360型)，自多肽的羧基端向 氨基端合成，得到肽树脂，再用TFA法将多肽从树脂上切割下来，初提得到粗品。
(2)多肽纯化：用美国的Waters高效液相色谱仪，C18反相色谱分离柱分离纯化后冷冻抽干。15个合成多肽纯度均为90％以上。纯化后的结果见图1。
(3)免疫原的制备
血蓝蛋白(keyhole limpet hemocyanin，KLH)为软体动物、节肢动物(蜘蛛和甲壳虫) 的血淋巴中发现的一种游离的蓝色呼吸色素，有较高免疫原性，为最常被选用的载体蛋 白。多肽片段与载体蛋白-血蓝蛋白(KLH)连接：取纯化后的多肽10mg与血蓝蛋白20 mg在缩合剂的催化下进行缩合反应，得到多肽-血蓝蛋白偶联物(多肽-KLH)。
多肽-KLH偶联实验步骤如下：
1)取20mg KLH用PBS(pH 7)溶解，使终浓度为10mg/ml，加入偶联试剂m-马 来酰亚胺基苯甲酰-N-羟基琥珀酰亚胺酯(MBS,Thermo Fisher)，在室温条件下反应1h， 形成KLH-MBS复合物，用PBS透析除去游离偶联试剂。
2)取10mg多肽(对于不含半胱氨酸的多肽片段，在其序列氨基端或羧基端引入半胱氨酸)，用PBS溶解，得到浓度为10mg/ml的溶液。
3)将多肽溶液与准备好的KLH-MBS混合，室温反应2h。
4)将反应混合液用PBS透析，终止反应，得抗原KLH-多肽。
5)蛋白定量，所得抗原浓度约为5mg/ml，其中多肽约为0.5mg/ml。
实施例3.动物免疫
动物：新西兰大耳白兔购于青岛康大生物科技有限公司。经过检疫无病原菌的一级 动物，体重1.5公斤左右，经一周的观察，兔子健康活泼，皮毛有光泽，饮食正常，进 行免疫。
具体免疫情况如下：取实施例2制备的多肽-KLH作为免疫抗原与弗氏完全佐剂(基础免疫)或弗氏不完全佐剂(加强免疫)混合，充分乳化，分别在兔的背部皮内多点注 射，每只动物注射总量不超过1.5ml(含KLH-多肽抗原约1mg，含多肽抗原表位约 100μg)。每个多肽抗原免疫3只兔子，每3周免疫1次，共免疫4次。四免后第10天，动 物耳缘静脉取血，分离血清，测定。另设1组为未偶联多肽抗原的单独KLH组 和1组为单纯佐剂组。KLH单独对照组使用与多肽-KLH组中等量的KLH与等体 积的弗氏完全佐剂混合进行注射，单纯佐剂组中则仅使用与多肽实验组终溶液 等体积的弗氏完全佐剂原浓度溶液进行注射。KLH单独对照组及单纯佐剂组使 用与多肽实验组同等给药方式及给药频次进行实验。
实施例4.多肽结合抗体测定
用有机化学固相合成的多肽片段(未偶联血蓝蛋白的)包被酶联反应板测定抗体结合效价，具体如下：
(1)包被：取多肽溶液(2mg/ml)100μl，加入0.05M碳酸盐缓冲液100ml中， 混匀，得包被溶液，浓度为2μg/ml。并设置空白对照和阴性对照。
(2)酶联反应板每孔加入多肽溶液100μl,置4℃过夜，而后弃去孔中液体。(为避免蒸发，板上应加盖或将板平放在底部有湿纱布的金属湿盒中)。
(3)封闭酶标反应孔：将封闭液(5％小牛血清)加满各反应孔，并去除各孔中的 气泡,37℃封闭40min。
(4)洗涤：吸干孔内反应液，用洗涤液注满板孔，放置3min略作摇动，吸干孔内 液，倾去液体后在吸水纸上拍干。洗涤3次。
(5)加样：在梯度稀释板，加入待检测样品，建立合适的浓度梯度，如1:500, 1:2000,1:8000,1:32000，1:128000，1:512000，1:2048000。将稀释好的样品加入酶标反 应孔中，每样品加3孔，每孔100μl，置于37℃，60min，然后用洗涤液满孔洗涤3 次，每次3min。
(6)加入酶标抗体：采用辣根过氧化物酶标记的羊抗兔IgG(ZSGB-BIO)作为二 抗，按1:20000用PBS(pH7.4)稀释，每孔加入100μl，37℃反应60min，然后用洗涤 液满孔洗涤3次，每次3min。
(7)显色：采用四甲基联苯胺(TMB)作为显色剂，每孔加入TMB-过氧化氢尿 素溶液100μl，置37℃避光放置3-5分钟，然后每孔加入终止液(2mol/L硫酸溶液)50μl 终止反应。
(8)检测：显色反应终止20min内，于450nm处测定光密度值。
结果见表2。可见，15个多肽抗原免疫家兔后，血清中均产生了针对多肽片段的 抗体，抗体结合效价较高，均达到105以上。单独KLH组和单纯佐剂组均未检测到效 价。
表2多肽序列特征和免疫效价汇总
实施例5.S蛋白结合抗体测定
操作流程同实施例4，S蛋白(北京百普赛斯生物科技股份有限公司)包被浓度为0.1μg/孔(1μg/ml)。结果见表2。可见，5～9#、11～14#多肽抗原血清中均产生了较高 的针对S蛋白的抗体，抗体结合效价：5#、6#、8#、11#、13#、14#多肽抗原达到105以 上，7#、9#、12#达到104以上。
实施例6.S蛋白RBD结构域结合抗体测定
以S蛋白RBD结构域(上海惠诚生物科技有限公司)为抗原进行包被，浓度1 μg/ml，4℃包被过夜。血清稀释以1:30稀释作为起始点，10倍梯度稀释。孵育时间2 h。以HRP偶联山羊抗兔抗体为二抗，1:20000稀释，孵育时间1h。TMB显色，450 nm波长检测吸光值。
结果见表2，可见，4～8#、10#多肽抗原血清中均产生了较高的针对RBD的抗体， 其中5#、8#多肽抗原产生的抗体结合效价达到105以上，4#、6#、7#、10#达到104以上， 与这些多肽序列位于S蛋白RBD结构域是一致的。11～14#抗血清虽然与S蛋白有较高 的结合活性，但与RBD无结合活性，与其多肽序列不在RBD结构域是一致的。
实施例7.免疫血清抗原竞争结合实验
以S蛋白RBD结构域为抗原进行包被，浓度1μg/ml，4℃包被过夜。将5～8#多肽 抗原血清等量混合后以1:4稀释(工作浓度)作为第一个点，3倍梯度稀释。每孔加入50μl血清先孵育30min后再加入50μl ACE-Fc(北京百奥莱博科技有限公司)(0.1 μg/ml)共孵育1h。以HRP偶联山羊抗人Fc抗体(Abcam，ab6721)为二抗，1:30000 稀释，孵育1h。TMB显色，450nm波长检测吸光值。
实验结果见图2。在1:4、1:12稀释比例观察到混合兔免疫血清对ACE2-RBD的结 合有一定的阻断作用。APN01为平行实验中的阳性对照。
以上，对本发明的实施方式进行了说明。但是，本发明不限定于上述实施方式。凡在本发明的精神和原则之内，所做的任何修改、等同替换、改进等，均应包含在本发明 的保护范围之内。
序列表
<110> 中国人民解放军总医院
<120> 新型冠状病毒S蛋白多肽抗原及其应用
<160> 110
<170> SIPOSequenceListing 1.0
<210> 1
<211> 18
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 1
His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr Ser
1 5 10 15
Ser Ala
<210> 2
<211> 16
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 2
Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser
1 5 10 15
<210> 3
<211> 13
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 3
His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly
1 5 10
<210> 4
<211> 12
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 4
Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys
1 5 10
<210> 5
<211> 23
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 5
Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile
1 5 10 15
Ala Asp Tyr Asn Tyr Lys Leu
20
<210> 6
<211> 22
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 6
Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro
1 5 10 15
Asp Asp Phe Thr Gly Cys
20
<210> 7
<211> 29
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 7
Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys
1 5 10 15
Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu
20 25
<210> 8
<211> 23
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 8
Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr
1 5 10 15
Gln Ala Gly Ser Thr Pro Cys
20
<210> 9
<211> 22
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 9
Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val
1 5 10 15
Gly Tyr Gln Pro Tyr Arg
20
<210> 10
<211> 13
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 10
Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys
1 5 10
<210> 11
<211> 12
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 11
Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu
1 5 10
<210> 12
<211> 23
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 12
Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro
1 5 10 15
Ser Lys Pro Ser Lys Arg Ser
20
<210> 13
<211> 20
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 13
Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp
1 5 10 15
Lys Tyr Phe Lys
20
<210> 14
<211> 14
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 14
Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser
1 5 10
<210> 15
<211> 13
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 15
Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val Leu Lys
1 5 10
<210> 16
<211> 12
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 16
Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met
1 5 10
<210> 17
<211> 18
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 17
Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe
1 5 10 15
Arg Val
<210> 18
<211> 27
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 18
Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe
1 5 10 15
Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe
20 25
<210> 19
<211> 18
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 19
Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg
1 5 10 15
Val Tyr
<210> 20
<211> 15
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 20
Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val
1 5 10 15
<210> 21
<211> 23
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 21
His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr Ser
1 5 10 15
Ser Ala Asn Asn Cys Thr Phe
20
<210> 22
<211> 30
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 22
Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn
1 5 10 15
Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu Met Asp Leu
20 25 30
<210> 23
<211> 20
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 23
Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro
1 5 10 15
Gln Gly Phe Ser
20
<210> 24
<211> 15
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 24
Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe
1 5 10 15
<210> 25
<211> 18
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 25
Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile
1 5 10 15
Thr Arg
<210> 26
<211> 26
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 26
Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile
1 5 10 15
Thr Arg Phe Gln Thr Leu Leu Ala Leu His
20 25
<210> 27
<211> 18
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 27
Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val
1 5 10 15
Ile Arg
<210> 28
<211> 18
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 28
Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile
1 5 10 15
Ala Asp
<210> 29
<211> 20
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 29
Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile
1 5 10 15
Ala Asp Tyr Asn
20
<210> 30
<211> 26
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 30
Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile
1 5 10 15
Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp
20 25
<210> 31
<211> 14
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 31
Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp
1 5 10
<210> 32
<211> 27
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 32
Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn
1 5 10 15
Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val
20 25
<210> 33
<211> 18
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 33
Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr
1 5 10 15
Lys Leu
<210> 34
<211> 26
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 34
Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr
1 5 10 15
Lys Leu Pro Asp Asp Phe Thr Gly Cys Val
20 25
<210> 35
<211> 23
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 35
Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro
1 5 10 15
Asp Asp Phe Thr Gly Cys Val
20
<210> 36
<211> 23
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 36
Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys
1 5 10 15
Pro Phe Glu Arg Asp Ile Ser
20
<210> 37
<211> 26
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 37
Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys
1 5 10 15
Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile
20 25
<210> 38
<211> 19
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 38
Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro
1 5 10 15
Phe Glu Arg
<210> 39
<211> 20
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 39
Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile
1 5 10 15
Ser Thr Glu Ile
20
<210> 40
<211> 15
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 40
Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile
1 5 10 15
<210> 41
<211> 26
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 41
Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr
1 5 10 15
Gln Ala Gly Ser Thr Pro Cys Asn Gly Val
20 25
<210> 42
<211> 27
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 42
Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln
1 5 10 15
Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg
20 25
<210> 43
<211> 17
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 43
Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly
1 5 10 15
Val
<210> 44
<211> 28
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 44
Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val
1 5 10 15
Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe
20 25
<210> 45
<211> 18
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 45
Arg Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu
1 5 10 15
Glu Ile
<210> 46
<211> 26
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 46
Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys Gln
1 5 10 15
Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe
20 25
<210> 47
<211> 27
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 47
Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser
1 5 10 15
Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys
20 25
<210> 48
<211> 29
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 48
Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser
1 5 10 15
Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser
20 25
<210> 49
<211> 14
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 49
Thr Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys
1 5 10
<210> 50
<211> 22
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 50
Thr Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu
1 5 10 15
Leu Asp Lys Tyr Phe Lys
20
<210> 51
<211> 24
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 51
Thr Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu
1 5 10 15
Leu Asp Lys Tyr Phe Lys Asn His
20
<210> 52
<211> 35
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 52
Thr Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu
1 5 10 15
Leu Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly
20 25 30
Asp Ile Ser
35
<210> 53
<211> 12
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 53
Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe
1 5 10
<210> 54
<211> 21
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 54
Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu
1 5 10 15
Asp Lys Tyr Phe Lys
20
<210> 55
<211> 13
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 55
Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu
1 5 10
<210> 56
<211> 13
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 56
Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu
1 5 10
<210> 57
<211> 21
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 57
Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp
1 5 10 15
Lys Tyr Phe Lys Asn
20
<210> 58
<211> 22
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 58
Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp
1 5 10 15
Lys Tyr Phe Lys Asn His
20
<210> 59
<211> 33
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 59
Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp
1 5 10 15
Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile
20 25 30
Ser
<210> 60
<211> 19
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 60
Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys
1 5 10 15
Tyr Phe Lys
<210> 61
<211> 20
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 61
Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys
1 5 10 15
Tyr Phe Lys Asn
20
<210> 62
<211> 18
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 62
Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr
1 5 10 15
Phe Lys
<210> 63
<211> 19
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 63
Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr
1 5 10 15
Phe Lys Asn
<210> 64
<211> 31
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 64
Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr
1 5 10 15
Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser
20 25 30
<210> 65
<211> 21
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 65
Glu Glu Leu Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp
1 5 10 15
Leu Gly Asp Ile Ser
20
<210> 66
<211> 25
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 66
Glu Glu Leu Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp
1 5 10 15
Leu Gly Asp Ile Ser Gly Ile Asn Ala
20 25
<210> 67
<211> 18
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 67
Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile
1 5 10 15
Asn Ala
<210> 68
<211> 10
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 68
Phe Asp Glu Asp Asp Ser Glu Pro Val Leu
1 5 10
<210> 69
<211> 18
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 69
His Lys Asn Asn Lys Ser Trp Met Glu Ser Gly Phe Arg Val Tyr Ser
1 5 10 15
Ser Ala
<210> 70
<211> 16
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 70
Lys His Thr Pro Ile Asn Leu Val Arg Gly Leu Pro Gln Gly Phe Ser
1 5 10 15
<210> 71
<211> 23
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 71
Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Asn Ile
1 5 10 15
Ala Asp Tyr Asn Tyr Lys Leu
20
<210> 72
<211> 23
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 72
Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Thr Ile
1 5 10 15
Ala Asp Tyr Asn Tyr Lys Leu
20
<210> 73
<211> 22
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 73
Ala Pro Gly Gln Thr Gly Asn Ile Ala Asp Tyr Asn Tyr Lys Leu Pro
1 5 10 15
Asp Asp Phe Thr Gly Cys
20
<210> 74
<211> 22
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 74
Ala Pro Gly Gln Thr Gly Thr Ile Ala Asp Tyr Asn Tyr Lys Leu Pro
1 5 10 15
Asp Asp Phe Thr Gly Cys
20
<210> 75
<211> 29
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 75
Ser Lys Val Gly Gly Asn Tyr Asn Tyr Arg Tyr Arg Leu Phe Arg Lys
1 5 10 15
Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu
20 25
<210> 76
<211> 23
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 76
Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr
1 5 10 15
Gln Ala Gly Ser Lys Pro Cys
20
<210> 77
<211> 22
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 77
Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Tyr Gly Val
1 5 10 15
Gly Tyr Gln Pro Tyr Arg
20
<210> 78
<211> 18
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 78
Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Gly Phe
1 5 10 15
Arg Val
<210> 79
<211> 27
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 79
Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Gly Phe
1 5 10 15
Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe
20 25
<210> 80
<211> 18
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 80
Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Gly Phe Arg
1 5 10 15
Val Tyr
<210> 81
<211> 15
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 81
Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Gly Phe Arg Val
1 5 10 15
<210> 82
<211> 23
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 82
His Lys Asn Asn Lys Ser Trp Met Glu Ser Gly Phe Arg Val Tyr Ser
1 5 10 15
Ser Ala Asn Asn Cys Thr Phe
20
<210> 83
<211> 30
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 83
Lys Ser Trp Met Glu Ser Gly Phe Arg Val Tyr Ser Ser Ala Asn Asn
1 5 10 15
Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu Met Asp Leu
20 25 30
<210> 84
<211> 20
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 84
Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Gly Leu Pro
1 5 10 15
Gln Gly Phe Ser
20
<210> 85
<211> 15
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 85
Lys His Thr Pro Ile Asn Leu Val Arg Gly Leu Pro Gln Gly Phe
1 5 10 15
<210> 86
<211> 18
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 86
Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Asn Ile
1 5 10 15
Ala Asp
<210> 87
<211> 18
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 87
Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Thr Ile
1 5 10 15
Ala Asp
<210> 88
<211> 20
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 88
Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Asn Ile
1 5 10 15
Ala Asp Tyr Asn
20
<210> 89
<211> 20
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 89
Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Thr Ile
1 5 10 15
Ala Asp Tyr Asn
20
<210> 90
<211> 26
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 90
Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Asn Ile
1 5 10 15
Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp
20 25
<210> 91
<211> 26
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 91
Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Thr Ile
1 5 10 15
Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp
20 25
<210> 92
<211> 14
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 92
Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Asn Ile Ala Asp
1 5 10
<210> 93
<211> 14
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 93
Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Thr Ile Ala Asp
1 5 10
<210> 94
<211> 27
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 94
Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Asn Ile Ala Asp Tyr Asn
1 5 10 15
Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val
20 25
<210> 95
<211> 27
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 95
Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Thr Ile Ala Asp Tyr Asn
1 5 10 15
Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val
20 25
<210> 96
<211> 18
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 96
Arg Gln Ile Ala Pro Gly Gln Thr Gly Asn Ile Ala Asp Tyr Asn Tyr
1 5 10 15
Lys Leu
<210> 97
<211> 18
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 97
Arg Gln Ile Ala Pro Gly Gln Thr Gly Thr Ile Ala Asp Tyr Asn Tyr
1 5 10 15
Lys Leu
<210> 98
<211> 26
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 98
Arg Gln Ile Ala Pro Gly Gln Thr Gly Asn Ile Ala Asp Tyr Asn Tyr
1 5 10 15
Lys Leu Pro Asp Asp Phe Thr Gly Cys Val
20 25
<210> 99
<211> 26
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 99
Arg Gln Ile Ala Pro Gly Gln Thr Gly Thr Ile Ala Asp Tyr Asn Tyr
1 5 10 15
Lys Leu Pro Asp Asp Phe Thr Gly Cys Val
20 25
<210> 100
<211> 23
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 100
Ala Pro Gly Gln Thr Gly Asn Ile Ala Asp Tyr Asn Tyr Lys Leu Pro
1 5 10 15
Asp Asp Phe Thr Gly Cys Val
20
<210> 101
<211> 23
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 101
Ala Pro Gly Gln Thr Gly Thr Ile Ala Asp Tyr Asn Tyr Lys Leu Pro
1 5 10 15
Asp Asp Phe Thr Gly Cys Val
20
<210> 102
<211> 23
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 102
Gly Asn Tyr Asn Tyr Arg Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys
1 5 10 15
Pro Phe Glu Arg Asp Ile Ser
20
<210> 103
<211> 26
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 103
Gly Asn Tyr Asn Tyr Arg Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys
1 5 10 15
Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile
20 25
<210> 104
<211> 19
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 104
Asn Tyr Asn Tyr Arg Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro
1 5 10 15
Phe Glu Arg
<210> 105
<211> 26
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 105
Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr
1 5 10 15
Gln Ala Gly Ser Lys Pro Cys Asn Gly Val
20 25
<210> 106
<211> 12
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 106
Asp Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met
1 5 10
<210> 107
<211> 27
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 107
Val Lys Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln
1 5 10 15
Pro Thr Tyr Gly Val Gly Tyr Gln Pro Tyr Arg
20 25
<210> 108
<211> 17
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 108
Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Tyr Gly
1 5 10 15
Val
<210> 109
<211> 28
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 109
Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Tyr Gly Val
1 5 10 15
Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe
20 25
<210> 110
<211> 18
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 110
Arg Asp Ile Asp Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu
1 5 10 15
Glu Ile
Claims (22)
1.一种多肽，其特征在于，所述多肽选自SEQ ID NO：1或SEQ ID NO：3-14中的任意一条。
2.一种多肽-载体蛋白偶联物，其特征在于，所述多肽-载体蛋白偶联物包括权利要求1所述的多肽以及与多肽偶联的载体蛋白，所述载体蛋白选自牛血清蛋白、卵清白蛋白、钥孔血蓝蛋白或酪蛋白，所述多肽通过连接序列与载体蛋白偶联。
3.根据权利要求2所述的多肽-载体蛋白偶联物，其特征在于，每个载体蛋白偶联5～30条多肽。
4.一种抗原，其特征在于，所述抗原包括一种或多种权利要求2或3所述的多肽-载体蛋白偶联物。
5.一种冠状病毒抗体检测试剂盒，其特征在于，所述试剂盒包括权利要求1所述的多肽或权利要求4所述的任一种抗原。
6.根据权利要求5所述的试剂盒，其特征在于，所述抗原为预包被抗原，所述预包被抗原包被于固相载体上，所述固相载体选自酶标板、膜载体或微球。
7.根据权利要求6所述的试剂盒，其特征在于，所述膜载体选自硝酸纤维素膜、玻璃纤维素膜或尼龙膜；所述膜载体上还包被有阳性对照物，多肽和阳性对照物按检测顺序在膜载体上依次设置。
8.根据权利要求7所述的试剂盒，其特征在于，所述试剂盒还包括如下至少之一：（1）酶标二抗，酶标二抗为HRP标记的二抗；（2）胶体金结合垫，胶体金结合垫上包被有胶体金标记的多肽和阳性对照物的特异性结合物；（3）标记垫，标记垫上包被有荧光标记的微球，微球上负载有阳性对照物的特异性结合物；所述阳性对照物选自鼠免疫球蛋白、人免疫球蛋白、羊免疫球蛋白或兔免疫球蛋白，相应地，阳性对照物的特异性结合物选自抗鼠免疫球蛋白、抗人免疫球蛋白、抗羊免疫球蛋白或抗兔免疫球蛋白。
9.权利要求1所述的多肽在制备治疗冠状病毒引起的疾病的药物中的应用，其特征在于，所述冠状病毒为SARS-CoV-2，所述药物为抗体或疫苗，所述疫苗为多肽疫苗或基因疫苗。
10.一种药物，其特征在于，所述药物为多肽疫苗或基因疫苗，所述多肽疫苗包含权利要求1所述的任一种多肽；基因疫苗包含编码权利要求1所述的任一种多肽的核酸。
11. 根据权利要求10所述的药物，其特征在于，所述多肽疫苗的多肽选自SEQ ID NO：5、SEQ ID NO：6、SEQ ID NO：8、SEQ ID NO：11、SEQ ID NO：13及SEQ ID NO：14中的任意一条或多条。
12. 一种多肽组合物，其特征在于，所述多肽组合物中至少包括SEQ ID NO：1或SEQ IDNO：3-14所示的多肽中的任意一条。
13. 根据权利要求12所述的多肽组合物，其特征在于，所述多肽组合物中至少包括SEQID NO：5、SEQ ID NO：6、SEQ ID NO：8、SEQ ID NO：11、SEQ ID NO：13或SEQ ID NO：14中的任意一条。
14. 一种多肽疫苗，其特征在于，所述多肽疫苗包括SEQ ID NO：1或SEQ ID NO：3-14所示的多肽中的任意一条或多条。
15. 根据权利要求14所述的多肽疫苗，其特征在于，所述多肽疫苗中至少包括SEQ IDNO：5、SEQ ID NO：6、SEQ ID NO：8、SEQ ID NO：11、SEQ ID NO：13及SEQ ID NO：14中的任意一条。
16.根据权利要求15所述的多肽疫苗，其特征在于，所述多肽疫苗包括多条肽段，所述多条肽段以串联形式存在；多条所述肽段经连接臂串联连接，连接臂选自甘氨酸、赖氨酸、AEA、Ava、ANP、β-丙氨酸、GAB或PEG；所述多肽疫苗中至少一条肽段串联1～10次。
17.根据权利要求16所述的多肽疫苗，其特征在于，所述多肽疫苗中至少一条肽段串联1～6次。
18.一种核酸疫苗，其特征在于，所述核酸疫苗包括核酸，所述核酸编码权利要求1所述的多肽，或者权利要求12所述的多肽组合物；所述核酸疫苗为DNA疫苗或RNA疫苗。
19.根据权利要求18所述的核酸疫苗，其特征在于，所述RNA疫苗为mRNA疫苗。
20. 一种重组蛋白疫苗，其特征在于，所述重组蛋白疫苗包含SEQ ID NO：1或SEQ IDNO：3-14中任一条或多条肽段。
21. 根据权利要求20所述的重组蛋白疫苗，其特征在于，所述重组蛋白疫苗是SEQ IDNO：1或SEQ ID NO：3-14中任一条或多条多肽与4～6个组氨酸或4个Gly 1个Ser重组而成的蛋白疫苗。
22. 根据权利要求21所述的重组蛋白疫苗，其特征在于，所述重组蛋白疫苗是SEQ IDNO：5、SEQ ID NO：6、SEQ ID NO：8、SEQ ID NO：11、SEQ ID NO：13及SEQ ID NO：14中的任意一条或多条多肽与4～6个组氨酸或4个Gly 1个Ser重组而成的蛋白疫苗。
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