CN112094327A - 基于新型冠状病毒rbd-sd1蛋白的截短体及其应用 - Google Patents
基于新型冠状病毒rbd-sd1蛋白的截短体及其应用 Download PDFInfo
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Abstract
本发明涉及生物医药领域,特别涉及基于新型冠状病毒RBD‑SD1蛋白的截短体及其应用。本发明公开的一种蛋白截短体,该蛋白截短体其具有如下所示的序列:(I)、具有如SEQ ID No.1所示的氨基酸序列;和/或(II)、如(I)所述氨基酸序列经取代、缺失或添加一个或多个氨基酸获得的氨基酸序列,且与(I)所述氨基酸序列功能相同的氨基酸序列;和/或(III)、与(I)或(II)所述氨基酸序列具有80%以上同一性的氨基酸序列。本发明公开的蛋白截短体能够诱导较强的体液免疫反应,具有良好的免疫原性,可应用于新型冠状病毒疫苗的开发及中和抗体的制备。
Description
技术领域
本发明涉及生物医药领域,特别涉及基于新型冠状病毒RBD-SD1蛋白的截短体及其应用。
背景技术
2020年1月12日,世界卫生组织(World Health Organization,WHO)正式将其命名为“2019新型冠状病毒”(2019 novel coronavirus,2019-nCoV),后被国际病毒分类学委员会命名为严重急性呼吸综合征2(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)。2月11日,WHO将新型感染的肺炎命名为新型冠状病毒肺炎(corona virusdisease 2019,COVID-19)。COVID-19给全人类都带来了巨大的挑战与压力,成为全球继甲型H1N1流感病毒疫情、野生型脊髓灰质炎病毒疫情、西非埃博拉疫情、巴西寨卡病毒疫情、刚果(金)埃博拉病毒疫情后第六次被认定为国际关注的突发公共卫生事件。
新型冠状病毒是一种具有包膜的、不分节段的正链单股RNA病毒,颗粒呈圆形或椭圆形,直径约80~120nm,属于网巢病毒目冠状病毒科Betacoronavirus。病毒粒子被宿主细胞提供的脂质双层所包裹,其中含有核酸及核衣壳蛋白,有三种主要蛋白:包膜蛋白(E蛋白)、膜蛋白(M蛋白)和刺突蛋白(S蛋白)。此病毒每组基因组长度约三万个核苷酸左右。SARS-CoV-2病毒的刺突蛋白(S蛋白)属于三聚体I类融合蛋白(GenBank ID:MN908947),其中分S1和S2两个亚基,表面刺突长度约23nm,宽7nm,S1解离时会造成S2的构象变化。在包膜刺突的表面具有宿主衍生出来的聚糖,而每一个三聚体都具有66个糖基化位点,SARS-CoV-2的糖基化已被发现可以促进其免疫逃避。通过S蛋白的三级结构分析,发现SARS-CoV-2S的各个结构域与SARS-CoVS的对应结构域对齐时,两种蛋白质之间的高度结构同源性。SARS-CoV-2的S1亚基可以分为N端结构域(NTD),受体结合域(RBD),亚域1和2(SD1和SD2)。受体结合域(RBD)与ACE2复合物的晶体结构进行测定后知,该晶体含C、N、O、S等元素,属于四方P的P41212空间群。RBD本身含有由反平行肽链组成的β1、β2、β3和β6四个β折叠层。在这一段蛋白核心中,于β3和β6中间有一段额外的插入,包括β4、β5的肽链以及α4和α5螺旋,形成了RBM,它主要含有负责与hACE2结合中的接触单元蛋白。迄今为止,没有任何疫苗被批准投入使用,但在临床治疗中,有多种病毒抑制药物被采纳。疫苗是防控SARS-CoV-2等一系列传染病最有效的手段。目前,包括中国在内的多个国家已成功分离出新型冠状病毒毒株,并开展了疫苗的研发。当前全球共有100多种新冠肺炎疫苗正在研发阶段,多个研发技术并行推进疫苗开发,包括灭活疫苗、核酸疫苗、重组蛋白疫苗、病毒载体疫苗等。灭活的完整病毒免疫原性相对较好。针对新冠肺炎的灭活疫苗目前已进入Ⅰ/Ⅱ期临床,但由于新冠肺炎的灭活疫苗的生产需要考虑需考产厂房的生物安全级别,因此生产规模受到了限制。疫苗具有灭活不完全的风险,安全问题是这类疫苗不可忽视和亟待克服的问题。重组蛋白疫苗是将某种病毒的目的抗原基因构建在表达载体上,将已构建的可表达蛋白的载体转化到细菌、酵母或哺乳动物或昆虫细胞中,在一定的诱导条件下,表达出大量的抗原蛋白,通过纯化后制备的疫苗。具有可抗原组分单一,安全高效等优点。目前大部分处于临床期或在研的SARS-CoV-2疫苗均采用S蛋白或其受体结合区域(RBD)作为主要免疫原。在此区域找到具有够诱导较强的体液免疫反应和具有良好的免疫原性的抗原片段是新型冠状病毒基因工程疫苗研究的关键。
发明内容
有鉴于此,本发明提供了基于新型冠状病毒RBD-SD1蛋白的截短体及其应用。该蛋白截短体能够诱导较强的体液免疫反应,具有良好的免疫原性,可应用于新型冠状病毒疫苗的开发及中和抗体的制备。
为了实现上述发明目的,本发明提供以下技术方案:
本发明提供了蛋白截短体,其具有如下所示的序列:
(I)、具有如SEQ ID No.1所示的氨基酸序列;和/或
(II)、如(I)所述氨基酸序列经取代、缺失或添加一个或多个氨基酸获得的氨基酸序列,且与(I)所述氨基酸序列功能相同的氨基酸序列;和/或
(III)、与(I)或(II)所述氨基酸序列具有80%以上同一性的氨基酸序列。
基于上述研究,本发明还提供了编码所述的蛋白截短体的核苷酸。
在本发明的一些具体实施方案中,所述核苷酸具有如下所示的序列:
(1)、具有如SEQ ID No.2所示的核苷酸序列;或
(2)、具有如SEQ ID No.2所示的核苷酸序列的互补序列;或
(3)、如(1)或(2)所示的核苷酸序列经取代、缺失或添加一个或多个碱基获得的核苷酸序列,且与(1)或(2)所示的核苷酸序列功能相同或相似的核苷酸序列;
(4)、与(1)、(2)或(3)所示的核苷酸序列至少有80%同一性的核苷酸序列;
本发明还提供了重组载体或表达盒,包括所述的核苷酸。
本发明还提供了转化或转染所述的重组载体或表达盒的宿主细胞。
基于上述研究,本发明还提供了所述的蛋白截短体、所述的核苷酸、所述的重组载体或表达盒或所述的宿主细胞在制备免疫原和/或抗原中的应用,作为抗原在制备针对新型冠状病毒的抗体中的应用,在制备新型冠状病毒的检测试剂或试剂盒中的应用和/或在制备预防和/或治疗新型冠状病毒引起的疾病的药物中的应用。
在本发明的一些具体实施方案中,所述免疫原或抗原包括新型冠状病毒或新型冠状病毒刺突蛋白S。
本发明还提供了针对新型冠状病毒的抗体,以所述的蛋白截短体、所述的核苷酸、所述的重组载体或表达盒或所述的宿主细胞作为抗原。
本发明还提供了新型冠状病毒的诊断试剂或试剂盒,包括所述的抗体以及可接受的辅料和/或载体。
本发明还提供了新型冠状病毒引起的疾病的诊断方法,以所述新型冠状病毒的诊断试剂或试剂盒检测新型冠状病毒的表达,根据表达量判断是否患有疾病。
本发明还提供了预防和/或治疗新型冠状病毒引起的疾病的药物,包括所述的抗体以及可接受的辅料。
新型冠状病毒引起的疾病的预防和/或治疗方法,给予所述的药物。
本发明提供的抗原片段T是来自新型冠状病毒(SARS-CoV-2)刺突蛋白S的RBD-SD1区域序列的截短体。本发明提供的抗原片段T具有作为S蛋白相似的抗原潜力,免疫产生的中和抗体能够有效抑制病毒的感染。与完整的S蛋白抗原相比,该抗原片段(蛋白截短体)不具有S蛋白的生物学功能(不具有S1亚基与S2亚基的功能,在病毒进入过程中只发挥辅助功能),该片段用于病毒载体疫苗的构建时具有更好的安全性,也更方便用于多价疫苗制备。抗原片段T能够诱导较强的体液免疫反应,具有良好的免疫原性,可应用于新型冠状病毒疫苗的开发及中和抗体的制备。
附图说明
为了更清楚地说明本发明实施例或现有技术中的技术方案,下面将对实施例或现有技术描述中所需要使用的附图作简单地介绍。
图1示重组蛋白T Western blot法鉴定;
图2示重组蛋白T的表达及纯化后SDS-PAGE电泳分析;
图3示重组蛋白T免疫小鼠血清的ELISA结果;
图4示为T蛋白免疫血清对假病毒感染靶细胞的中和活性分析。
具体实施方式
本发明公开了基于新型冠状病毒RBD-SD1蛋白的截短体及其应用,本领域技术人员可以借鉴本文内容,适当改进工艺参数实现。特别需要指出的是,所有类似的替换和改动对本领域技术人员来说是显而易见的,它们都被视为包括在本发明。本发明的方法及应用已经通过较佳实施例进行了描述,相关人员明显能在不脱离本发明内容、精神和范围内对本文所述的方法和应用进行改动或适当变更与组合,来实现和应用本发明技术。
本发明提供的一种蛋白的截短体,该蛋白的截短体为如下(1)或(2)所示:
(1)SEQ ID No.1所示的蛋白;
(2)将SEQ ID No.1所示的氨基酸序列经过一个或几个氨基酸残基的取代和/或缺失和/或添加且功能相同的蛋白质;
所述的蛋白截短体的编码基因为如下1)-3)任一所示:
1)SEQ ID No.2所示的DNA分子;
2)在严格条件下与1)限定的DNA分子杂交且编码权利要求1中(1)或(2)所述的蛋白截短体的DNA分子;
3)与1)或2)限定的DNA分子具有90%以上的同一性且编码权利要求1中(1)或(2)所述的蛋白的截短体的DNA分子。
含有上述编码基因的重组载体、表达盒、转基因细胞系或重组菌也属于本发明的保护范围。
所述重组载体是将SEQ ID No.2所示的DNA分子、插入表达载体合适的限制性酶切位点之间,使其核苷酸序列可操作的与表达调控序列相连接,作为本发明的一个最优选的实施方案,优选为将SEQ ID No.2所示的DNA分子插入到质粒pPIC9K的SnaBI与NotI位点间。
上述蛋白截短体、上述基因或上述重组载体在制备免疫原和/或抗原中的应用也属于本发明的保护范围;
所述免疫原或抗原是针对新型冠状病毒或新型冠状病毒刺突蛋白S的。
上述到蛋白截短体、上述基因或上述重组载体作为抗原在制备针对新型冠状病毒的抗体中的应用也属于本发明的保护范围。
上述的蛋白截短体、上述基因或上述重组载体在制备预防和/或治疗新型冠状病毒引起的疾病的产品中的应用也属于本发明的保护范围;
所述新型冠状病毒(SARS-CoV-2)具体为引起新型冠状病毒肺炎(COVID-19)的病原体。
S蛋白的生物学功能主要是通过其受体结合域(Receptor-binding domain,RBD)结合宿主ACE2受体,从而使得新型冠状病毒进入宿主细胞。暴露于S蛋白表面的受体结合域(RBD)及亚域(Subdomains 1,SD1)称为RBD-SD1(aa319-591)在S蛋白功能的发挥中具有关键作用,且RBD-SD1区域含有丰富S蛋白抗原表位。本发明提供的抗原片段T是来自新型冠状病毒(SARS-CoV-2)刺突蛋白S的RBD-SD1区域序列的截短体。本发明提供的抗原片段T具有作为S蛋白相似的抗原潜力,免疫产生的中和抗体能够有效抑制病毒的感染。与完整的S蛋白抗原相比,该抗原片段不具有S蛋白的生物学功能(不具有S1亚基与S2亚基的功能,在病毒进入过程中只发挥辅助功能),该片段用于病毒载体疫苗的构建时具有更好的安全性,也更方便用于多价疫苗制备。抗原片段T能够诱导较强的体液免疫反应,具有良好的免疫原性,可应用于新型冠状病毒疫苗的开发及中和抗体的制备。
下述实施例中所使用的实验方法如无特殊说明,均为常规方法。
下述实施例中所用的材料、试剂等,如无特殊说明,均可从商业途径得到。
6周龄Balb/C雌性小鼠购自北京维通利华实验动物技术有限公司,许可证号:SCXK-(京)2019-0010。
山羊抗小鼠IgGH&L(HRP)购自Abcam中国(货号:ab205719)。
RBD-SD1蛋白购自南京金斯瑞生物科技有限公司货号:P9FC001。
Huh7细胞由军事兽医研究所保存。
假病毒构建过程中使用的含新型冠状病毒S基因质粒pcDNA3.1(+)-S购自基因通用生物有限公司;pNL4.3-Luc.R-E-质粒使用文献“王茂鹏,李昌,杜寿文,朱羿龙,朱娜,孙丹丹,金宁一.HIV-1B亚型假病毒的制备与鉴定[J].军事医学,2014,38(01):31-34.”中质粒改造,可从军事兽医研究所获得。
下面结合实施例,进一步阐述本发明:
实施例1重组质粒的获得
所述重组载体是将SEQ ID No.1所示的DNA分子、插入pPIC9K SnaBI与NotI位点,委托上海捷瑞生物工程有限公司合成,得到重组质粒。
重组质粒pPIC9K-T测序,结果正确。
实施例2重组蛋白T的表达及纯化
酵母菌的转化与筛选:表达载体pPIC9K-T构建好之后,大量提取质粒DNA,用BglII线性化后,取5μg线性化质粒,通过电击法转化毕赤酵母GS115感受态(P.pastoris GS115菌株购自Invitrogen公司),电击转化后的感受态细胞涂布于MD固体平板,30℃恒温培养箱倒置培养2-3天,至转化子长出。将转化子挑取于YPD+G418(700μg/mL)培养基上,在30℃下培养1-2d后,挑选较大的白色单菌落,接种至3mLBMGY培养基的培养管中,30℃,220rpm摇床培养48h,将摇床培养48h的菌液3000×g离心15min,去上清,培养管中再加入1mL含有0.5%甲醇的BMMY培养基,在30℃、220rpm诱导培养,诱导培养48h后,3000×g离心5min,取上清用于SDS-PAGE检测,从中筛选出有特异表达条带的转化子,保存菌种。
15L发酵罐高密度培养:发酵罐参数设置为pH5.0,温度30℃,转速1000rpm,通风比为2:1。培养约16h后,待葡萄糖耗尽,溶氧迅速上升,开始流加碳源(400mL25%葡萄糖)约8h左右待菌体湿重达到160g/L时,开始进行混饲培养(100mL的25%甘油+12.5mL甲醇),混饲4h后,开始流加甲醇,进入诱导表达阶段。开始诱导后,每隔12h取发酵样品跑SDS-PAGE电泳,随着诱导时间的延长,目的条带蛋白量增加,当蛋白量不再增加时,停止发酵,将发酵液离心(8000rpm,20min,4℃),收集上清液,用于后续纯化。Western blot法鉴定目的蛋白(抗体购自购自南京金斯瑞生物科技有限公司,货号:A02038)。结果如图1所示。
重组蛋白T:重组蛋白RBD-SD1的纯化过程如下:将发酵液4℃,12000×g离心15min,收集上清,用终浓度50%的硫酸铵进行分级沉淀,获得粗纯化的目的蛋白,经12000rpm离心20分钟,沉淀下来的蛋白再以10mM的甘氨酸-氢氧化钠缓冲液(pH10.5)溶解,经过SDS-PAGE电泳,目标蛋白即可明显富集,采用AKTA SERVICE纯化仪进行纯化,以上样品经阴离子柱(Hi Trap Q Sepharose XL 5mL)进行离子交换层析,洗脱液为1M的氯化钠的pH10.5的甘氨酸-氢氧化钠缓冲液,收集各峰组分,产物进行SDS-PAGE分析,确定收集的目标峰,即为纯化的重组蛋白RBD蛋白,结果如图2所示。
实施例3抗原免疫活性测定
(一)免疫方法
分组:
动物选取6周龄Balb/C雌性小鼠,分为PBS组,RBD-SD1蛋白+MF59佐剂组、T蛋白+MF59佐剂组,每组10只小鼠。
免疫方式:
PBS组,RBD-SD1蛋白+MF59佐剂组、T蛋白+MF59佐剂组,采取腿部肌肉注射,3周免疫一次(分别在第0天、第21天和42天免疫),10μg蛋白/只(蛋白浓度50μg/mL),PBS组免疫体积为200μL/只,共免疫3次,首次免疫采用MF59佐剂,以1:1混合。
采血方式及时间:
尾静脉采血,采血时间为免疫前采血1次,每次免疫后第7天采血1次。
(二)血清中抗体滴度测定
1、所采各组小鼠的血液置于室温凝固收缩2小时后,6000rpm离心8分钟,收集上清,即为血清。
2、重组蛋白T(步骤二制备)铺板(Nunc酶标板),0.5μg/孔,4℃过夜,用PBST(含体积百分含量0.5%吐温-20)溶液洗板4次,每次5分钟;将板用5g/100ml的脱脂牛奶的PBST(含体积百分含量0.5%吐温-20)溶液37℃封闭2小时,PBST(含体积百分含量0.5%吐温-20)溶液洗板4次,每次5分钟;加入步骤1得到的免疫血清,37℃孵育1小时,PBST(含体积百分含量0.5%吐温-20)溶液洗板4次,每次5分钟;加入HRP标记的Goat anti-mouse IgG抗体,37℃孵育1小时,PBST(含体积百分含量0.5%吐温-20)溶液洗板4次,每次5分钟;100μL/孔加入TMB显色液,室温避光反应15分钟,加入2M硫酸终止反应,OD450读数(仪器为TECAN多功能酶标仪)。
PBS组,T蛋白组血清中抗体滴度结果如图3所示。图3表明,抗原T诱导的抗体反应水平均与抗原RBD-SD1诱导的抗体反应水平相当。
(三)假病毒感染中和实验
采用经典的假病毒的感染中和实验方法(Arnab Basu,et al.JOURNALOFVIROLOGY,Apr.2011,p.3106-3119;L.Du,et.Res.Commun.(2010),doi:10.1016/j.bbrc.2010.05.161)验证抗原片段T诱导产生有效中和抗体的能力,为抗原片段T应用于疫苗或中和抗体的开发提供依据。
具体步骤如下:
1、假病毒包装:
293T细胞以5x105Cell/孔接种至6孔板,37℃,5%CO2细胞培养箱内培养过夜。转染前更换Opti-MEM(Gibco)培养基1mL/孔;3μg pNL4.3-Luc.R-E-质粒与3μg pCDNA3.1(+)-S质粒共转染293T细胞,转染试剂Lipofectamine3000(购自Invitrogen公司)。转染48小时后,离心取上清分装冻存于-80℃冰箱,即为假病毒溶液。
2、假病毒感染中和实验:
于实验前一天,按1x104Cell/孔将Huh7细胞铺于96孔板,待到次日生长至80%融合度。将10μL步骤(二)制备的PBS组,RBD-SD1组、重组蛋白T组免疫血清与100μL步骤1制备的假病毒溶液混合于1mLDMEM培养基中,37℃孵育2小时得到混合液。取200μL/孔混合液替换96孔板细胞培养基,每组血清设置4个复孔,将96孔板置于37℃,5%CO2,培养箱中培养2h,更换新鲜的含10%FBS的DMEM培养基,继续培养48小时后,按照One-LumiTM萤火虫荧光素酶报告基因检测试剂盒说明,使用TECAN多功能酶标仪测定各孔发光值并计算假病毒感染抑制率,结果如图4所示。
图4表明:抗原截短体T能够诱导较强的体液免疫反应,具有良好的免疫原性,可应用于新型冠状病毒疫苗的开发及中和抗体的制备。
以上所述仅是本发明的优选实施方式,应当指出,对于本技术领域的普通技术人员来说,在不脱离本发明原理的前提下,还可以做出若干改进和润饰,这些改进和润饰也应视为本发明的保护范围。
序列表
<110> 军事科学院军事医学研究院军事兽医研究所
<120> 基于新型冠状病毒RBD-SD1蛋白的截短体及其应用
<160> 2
<170> SIPOSequenceListing 1.0
<210> 1
<211> 219
<212> PRT
<213> 人工序列(Artificial Sequence)
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Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val
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Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala
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Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp
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Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser
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Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala
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Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro
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Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro
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Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr
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attacaaact tgtgcccttt tggtgaagtt tttaacgcca ccagatttgc atctgtttat 60
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gcatcatttt ccacttttaa gtgttatgga gtgtctccta ctaaattaaa tgatctctgc 180
tttactaatg tctatgcaga ttcatttgta attagaggtg atgaagtcag acaaatcgct 240
ccagggcaaa ctggaaagat tgctgattat aattataaat taccagatga ttttacaggc 300
tgcgttatag cttggaattc taacaatctt gattctaagg ttggtggtaa ttataattac 360
ctgtatagat tgtttaggaa gtctaatctc aaaccttttg agagagatat ttcaactgaa 420
atctatcagg ccggtagcac accttgtaat ggtgttgaag gttttaattg ttactttcct 480
ttacaatcat atggtttcca acccactaat ggtgttggtt accaaccata cagagtagta 540
gtactttctt ttgaacttct acatgcacca gcaactgttt gtggacctaa aaagtctact 600
aatttggtta aaaacaaatg tgtcaatttc aacttcaatg gtttaacagg cacaggt 657
Claims (10)
1.蛋白截短体,其特征在于,其具有如下所示的序列:
(I)、具有如SEQ ID No.1所示的氨基酸序列;和/或
(II)、如(I)所述氨基酸序列经取代、缺失或添加一个或多个氨基酸获得的氨基酸序列,且与(I)所述氨基酸序列功能相同的氨基酸序列;和/或
(III)、与(I)或(II)所述氨基酸序列具有80%以上同一性的氨基酸序列。
2.编码如权利要求1所述的蛋白截短体的核苷酸。
3.如权利要求2所述的核苷酸,其特征在于,所述核苷酸具有如下所示的序列:
(1)、具有如SEQ ID No.2所示的核苷酸序列;或
(2)、具有如SEQ ID No.2所示的核苷酸序列的互补序列;或
(3)、如(1)或(2)所示的核苷酸序列经取代、缺失或添加一个或多个碱基获得的核苷酸序列,且与(1)或(2)所示的核苷酸序列功能相同或相似的核苷酸序列;
(4)、与(1)、(2)或(3)所示的核苷酸序列至少有80%同一性的核苷酸序列。
4.重组载体或表达盒,包括如权利要求2或3所述的核苷酸。
5.转化或转染如权利要求4所述的重组载体或表达盒的宿主细胞。
6.如权利要求1所述的蛋白截短体、如权利要求2或3所述的核苷酸、如权利要求4所述的重组载体或表达盒或如权利要求5所述的宿主细胞在制备免疫原和/或抗原中的应用和/或作为抗原在制备针对新型冠状病毒的抗体中的应用。
7.如权利要求1所述的蛋白截短体、如权利要求2或3所述的核苷酸、如权利要求4所述的重组载体或表达盒或如权利要求5所述的宿主细胞在制备新型冠状病毒的检测试剂或试剂盒中的应用和/或在制备预防和/或治疗新型冠状病毒引起的疾病的药物中的应用。
8.针对新型冠状病毒的抗体,其特征在于,以如权利要求1所述的蛋白截短体、如权利要求2或3所述的核苷酸、如权利要求4所述的重组载体或表达盒或如权利要求5所述的宿主细胞作为抗原表达,制备抗体。
9.新型冠状病毒的诊断试剂或试剂盒,其特征在于,包括如权利要求8所述的抗体以及可接受的辅料和/或载体。
10.预防和/或治疗新型冠状病毒引起的疾病的药物,其特征在于,包括如权利要求8所述的抗体以及可接受的辅料。
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