CN115806597A - 一种鉴定或鉴别新冠突变型抗原的抗体、试剂及方法 - Google Patents
一种鉴定或鉴别新冠突变型抗原的抗体、试剂及方法 Download PDFInfo
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Abstract
本发明提供了一种鉴定或鉴别新冠突变型抗原的抗体、试剂及方法。利用本发明抗体、试剂或方法能够快速、准确地鉴定或鉴别新冠突变型抗原，且检测效率高、成本低。
Description
技术领域
本发明属于蛋白检测领域。更具体地，涉及一种鉴定或鉴别新冠突变型抗原的抗体、试剂及方法。
背景技术
新型冠状病毒(SARS-CoV-2)属于冠状病毒科，为不分节段的单股正链RNA病毒。它编码4种结构蛋白(S、E、M和N蛋白)，其中，N蛋白是病毒粒子的核心成分，其蛋白全长419个氨基酸，大小为43-50kDa。N蛋白有三个相对保守的结构域，其中一域可与病毒基因组RNA相互缠绕形成病毒核衣壳，在病毒RNA的合成过程中发挥着重要的作用，与病毒基因组复制和调节细胞信号通路有关。N蛋白是一个磷酸化蛋白，磷酸化能够调节N蛋白的构象，增强与病毒蛋白的构象，增强与病毒RNA的亲和力。在核衣壳包装过程中，N蛋白可与M蛋白相互作用，促进核衣壳包装成病毒粒子。
N抗原检测呈阳性可作为新冠早期感染的直接证据。然而，新冠病毒N蛋白上出现的各种突变意味着抗原逃逸检测抗体对的几率上升，导致试剂盒面临无法检出突变株病毒的风险。因此，开发一种能够结合突变型N蛋白的单克隆抗体以及鉴别新冠突变株的试剂盒具有重要意义。
发明内容
本发明的目的是提供一种鉴定或鉴别新冠突变型抗原的抗体、试剂及方法。
在一些实施方案中，本发明可以包括下述一项或多项：
一种多肽，其中，所述多肽包含SEQ ID NO:9所示的新冠突变型抗原的N蛋白第58-69位氨基酸片段；或所述多肽包含SEQ ID NO:8所示的新冠突变型抗原的N蛋白第44-84位氨基酸片段；或所述SEQ ID NO:7所示的新冠突变型抗原的N蛋白第44-180位氨基酸片段。
本发明还提供了包含所述多肽的免疫原、及相关的杂交瘤细胞。
本发明的另一目的是提供了一种抗体，其中，所述抗体结合SEQ ID NO:7、或SEQID NO:8，或SEQ ID NO:9所示的任意氨基酸片段。
本发明还提供了一种抗体组合，所述抗体组合包括抗体1和抗体2，所述抗体1为新冠突变型抗原的N蛋白抗体，所述抗体2结合新冠病毒N蛋白第1-43、85-95、44-180或248-364位氨基酸片段。
抗体1结合44-180aa(SEQ ID NO:7)、44-84aa(SEQ ID NO:8)或58-69aa(SEQ IDNO:9)。
抗体2结合1-43aa(SEQ ID NO:2)、85-95aa(SEQ ID NO:10)、44-180aa(SEQ IDNO:3)或248-364aa(SEQ ID NO:5)。
进一步可选地，所述抗体组合还包括抗体3，所述抗体3结合第1-43、85-95、44-180或248-364位氨基酸片段。
可选地，当抗体2结合新冠病毒N蛋白第44-180位氨基酸片段时，抗体3也可以是结合新冠病毒N蛋白第44-180位氨基酸片段的抗体；
可选地，当抗体2位结合其它片段的抗体时，所述抗体3与抗体2的结合片段不同。
本发明还提供了一种鉴别新冠突变型抗原的检测试剂，其中，所述试剂包括上述抗体或上述所述的抗体组合。
本发明还提供了一种鉴定或鉴别新冠突变型抗原的免疫层析试剂。
本发明还提供了一种鉴定或鉴别新冠突变型抗原的方法。
利用本发明抗体、试剂或方法能够快速、准确地鉴定或鉴别新冠突变型抗原，且检测效率高、成本低，检测特异性和灵敏度高、与新冠突变型抗原反应活性好。
具体实施方式
本发明涉及一种多肽，其中，所述多肽包含SEQ ID NO:9所示的新冠突变型抗原的N蛋白第58-69位氨基酸片段。
在一些实施方式中，本发明涉及一种多肽，其中，所述多肽包含SEQ ID NO:8所示的新冠突变型抗原的N蛋白第44-84位氨基酸片段。
在一些实施方式中，本发明涉及一种多肽，其中，所述多肽包含SEQ ID NO:7所示的新冠突变型抗原的N蛋白第44-180位氨基酸片段。
在一些实施方式中，本发明还提供一种免疫原，其中，所述免疫原包含如上所述的多肽。
在一些实施方式中，本发明还提供一种杂交瘤细胞，其中，所述杂交瘤细胞由如上所述的免疫原免疫得到的B淋巴细胞与骨髓瘤细胞融合得到。
在一些实施方式中，本发明还提供了一种抗体，其中，所述抗体结合SEQ ID NO:7所示的氨基酸片段；在一些实施方式中，所述抗体结合SEQ ID NO:8所示的氨基酸片段；在一些实施方式中，所述抗体结合SEQ ID NO:9所示的氨基酸片段。在一些实施方式中，所述抗体不结合新冠病毒N蛋白第63位未突变的抗原
在本发明中，术语“抗体”在最广义上使用，其可以包括全长单克隆抗体，双特异性或多特异性抗体，以及嵌合抗体，只要它们展示所需的生物学活性。
在一些实施方式中，本发明还提供了一种抗体组合，所述抗体组合包括抗体1和抗体2，所述抗体1为如上所述的抗体，所述抗体2结合新冠病毒N蛋白第1-43、85-95、44-180或248-364位氨基酸片段；在一些实施方式中，所述抗体2结合新冠病毒N蛋白第85-95位氨基酸片段。
在一些实施方式中，所述抗体组合用于鉴定新冠突变型抗原，所述突变型抗原包含新冠病毒N蛋白第63位突变为非天冬氨酸的其它氨基酸。新冠突变株以B.1.617.2为例，其N蛋白携带D63G+R203M+D377Y位点突变；其它例如Delta-plus的N蛋白携带D63G+R203M+G215C+D377Y位点突变。本发明鉴别的“突变型抗原”包括N蛋白携带D63位点突变的谱系和/或亚型。
在一些实施方式中，抗体结合新冠病毒N蛋白对应的氨基酸片段是指抗体能够结合所述氨基酸片段，但该氨基酸片段不一定是最小结合片段。
在一些实施方式中，当待测样品中含所述突变型抗原(即N蛋白携带D63G位点突变)时，抗体1和抗体2能以双抗体夹心的方式检测所述突变型抗原；在一些实施方式中，当待测样品中不含所述突变型抗原(即N蛋白63位点为天冬氨酸)时，抗体1不与之发生结合。
在一些实施方式中，所述抗体组合可以进一步包含抗体3，所述抗体3结合新冠病毒N蛋白第1-43、85-95、44-180或248-364位氨基酸片段；在一些实施方式中，当抗体2结合新冠病毒N蛋白第44-180位氨基酸片段时，抗体3也可以是结合新冠病毒N蛋白第44-180位氨基酸片段的抗体；在一些实施方式中，当抗体2位结合其它片段的抗体时，所述抗体3与抗体2的结合片段不同。
在一些实施方式中，当待测样品中含所述突变型抗原(即N蛋白携带D63G位点突变)时，抗体1和抗体2、抗体2和抗体3均能以双抗体夹心的方式检测所述突变型抗原；在一些实施方式中，当待测样品中不含所述突变型抗原(即N蛋白D63位点为天冬氨酸)时，抗体1不与之发生结合、但抗体2和抗体3仍能以双抗体夹心的方式检测样品中的抗原；鉴于此，完成对突变型抗原的N蛋白是否携带D63位点突变的鉴别。
在一些实施方式中，本发明还提供了一种鉴别新冠突变型抗原的检测试剂，其中，所述试剂包括如上所述的抗体或如上所述的抗体组合。本发明所述试剂应做广义理解，其主要指承载免疫检测相关试剂的工具；在一些实施方式中，还可以进一步包括一些配套试剂，其可以是例如工作液，但不限于此。
在一些实施方式中，本发明还提供了一种鉴别新冠突变型抗原的免疫层析试纸，其中，所述免疫层析试纸包括底板、样品垫、结合垫、硝酸纤维素膜和吸水垫，所述硝酸纤维素膜上可选地设置有质控线、检测线1和检测线2，所述结合垫上设置有抗体2，所述检测线1上包被抗体1、所述检测线2上包被抗体3。
在一些实施方式中，可以使用任何适当的体外测定，基于细胞的测定，体内测定，动物模型等检测本发明抗体的效果如结合活性和/交叉反应性。在一些实施方式中，所述测定可以包括例如ELISA，FACS结合测定，Biacore，竞争性结合测定等。在一些实施方式中，例如在ELISA中表征本发明的抗体与抗原(抗原肽)结合的反应性，例如通过过氧化物酶标记的ELISA法读取405nm处的反应值≧0.5确定为有较好反应性，可用于免疫测定。
在一些实施方式中，其中所述抗体任选地用可检测的标记物标记。在一些实施方式中，可检测的标记例如胶体金、放射性标记、发光物质、有色物质、酶，例如荧光标记、发色团标记、电子致密标记，例如放射性同位素、荧光团、罗丹明及其衍生物、荧光素酶、荧光素、辣根过氧化物酶、碱性磷酸酶、β-半乳糖苷酶、葡糖淀粉酶、溶菌酶、糖类氧化酶、葡萄糖氧化酶、半乳糖氧化酶，和葡萄糖-6-磷酸脱氢酶，生物素/抗生物素蛋白，自旋标记。
在一些实施方式中，其中所述抗体任选地结合至固相和/或结合配偶体。在一些实施方式中，固相可以是例如磁性颗粒，胶乳粒子，微量滴定板，硝酸纤维素膜，玻璃纤维素膜，尼龙膜或微流控芯片；结合配偶体可以是例如生物素/抗生物素蛋白，生物素/链霉抗生物素蛋白。
在一些实施方式中，本发明还提供了一种免疫层析试纸，所述免疫层析试纸包括底板、样品垫、结合垫、硝酸纤维素膜和吸水垫，所述硝酸纤维素膜上可选地设置有质控线、检测线1和检测线2，所述样品垫上设置有生物素化的抗体1，所述结合垫上设置有抗体2，所述检测线1上包被亲和素，所述检测线2上包被抗体3。
在一些实施方式中，本发明还提供了一种鉴别新冠突变型抗原的方法，其中，所述方法包括使用如上所述的检测试剂或如上所述的免疫层析试纸，与待测样品接触。在一些实施方式中，当检测线1和检测线2同时显色，则判定为样品中包含新冠病毒N蛋白第63位突变的抗原；当检测线2显色，检测线1不显色时，则判定为样品中包含新冠病毒N蛋白第63位未突变的抗原。
在一些实施方式中，待测样品选自离体的唾液、血液、血浆、血清、咽拭子，鼻拭子、尿液等。
下面将结合实施例对本发明的实施方案进行详细描述。
实施例1新冠N蛋白单克隆抗体的制备
1、免疫动物
取8～12周龄与骨髓瘤细胞同种系的BALB/c小鼠，以含蛋白质100μg/只的2019-nCoV N蛋白突变抗原(SEQ ID NO:1，以下命名为Gx-nCoVN)与等量福氏完全佐剂充分混匀，注入小鼠腹腔内，每隔2周100μg/只的Gx-nCoVN与等量福氏不完全佐剂充分混匀，多次注入小鼠腹腔内加强免疫。经检测小鼠血清(间接ELISA法)，滴度在1∶2000以上者可用于融合，融合前3天经小鼠腹腔内再次加强免疫，剂量为50μg/只。
2、饲养细胞的制备
以BALB/c鼠腹腔巨噬细胞作饲养细胞。在融合前1天，BALB/c鼠拉颈处死，75％酒精全身浸泡，超净台内，无菌操作下用剪刀剪开腹部皮肤，暴露腹膜，用注射器腹腔注入RPMI 1640基础培养液5mL，反复冲洗，回收冲洗液，1000rpm，离心5分钟，留沉淀，用RPMI1640筛选培养液(含HAT的RPMI 1640完全培养液中)重悬，调整细胞浓度1×105个/mL，加入96孔板，150μL/孔，37℃，5％CO2培养过夜。
3、免疫脾细胞的制备
小鼠末次免疫后三天，在无菌条件下取出脾脏，置于平皿中，RPMI 1640基础培养液冲洗一次，放于小烧杯的尼龙网上磨碎过滤，制成细胞悬液。离心，弃上清，RPMI 1640基础培养液重悬，如此重复三次，计数。
4、细胞融合
(1)取40mL HAT培养液，15mL DMEM无血清培养液和1mL50％PEG(M12000)分别置于37℃水浴中预温；
(2)分别取小鼠骨髓瘤细胞Sp2/0(菲鹏生物股份有限公司保存)(2～5×107)、上述免疫脾细胞(108)悬液加入50mL离心管中混匀，并加DMEM无血清培养液至40mL。离心10分钟，倒尽上清液，混匀；
(3)将离心管置于37℃预温的水中，取0.7mL预温的50％PEG溶液，静置90秒钟。立即滴加37℃15mL预温的无血清培养液；
(4)补加DMEM无血清培养液至40mL，离心10分钟，倒尽上清液。加40mL含15％～20％胎牛血清的HAT培养液。用吸管混匀，滴加到已含有饲养细胞的4块96孔细胞培养板的小孔中，每孔2滴，置37℃、7％CO2的培养箱中培养。
5、杂交瘤细胞的选择培养
免疫小鼠脾细胞与小鼠骨髓瘤细胞，经PEG处理后，形成多种细胞成分的混合体，其中包括未融合的骨髓瘤细胞和免疫脾细胞；骨髓瘤细胞的共核体和免疫脾细胞的共核体，以及骨髓瘤细胞和免疫脾细胞的异核体。仅后者才能形成杂交瘤细胞。为此，在这多种细胞混合体中必须除去未融合的细胞和同种融合的共核体，并选择出真正的杂交细胞。因此，在细胞融合后第1，3，5，7天用前述的HAT培养液换液培养。
6、特异性抗体的检测及杂交瘤细胞克隆化
吸取每个培养孔的上清液，用间接ELISA法检测出培养液中含特异性识别Gx-nCoVN的抗体的培养孔。采用间接ELISA法鉴定细胞培养上清的交叉反应性，用Gx-nCoVN包被96孔板，封闭，加入杂交瘤细胞培养液上清孵育，加二抗，测405nm反应值，挑选反应值(0.5以上)比较高的细胞株制备抗体进行下一轮筛选实验。筛选得到以下有较好反应性的抗体。
实施例2 14Q11、19L1抗体的检测特异性
将2019-nCoV野生型N蛋白重组抗原以及携带以下位点的突变型N蛋白全长抗原分别包被微孔，以PBS+20％NBS为稀释液，稀释单抗为一抗浓度到1ug/ml，以羊抗鼠IgG-HRP为二抗，鉴定抗体的反应情况，反应情况如下：
表1
以上结果表明14Q11以及19L1两株抗体对野生型抗原反应性较弱，但是对N蛋白携带D63G位点突变的突变型抗原反应性较强，说明此两株抗体特异性识别携带该位点突变的突变型抗原。
实施例3抗体结合片段的鉴定
采用不同片段的Gx-nCoVN抗原分别包被微孔，以PBS+20％NBS为稀释液，稀释单抗为一抗浓度到1ug/ml，以羊抗鼠IgG-HRP为二抗，依据单抗对不同抗原的反应情况来确定单抗片段，具体数据如下：
表2
| 抗体编号 | 14Q11 | 19L1 |
| 1-43aa(SEQ ID NO:2) | 0.0093 | 0.0084 |
| 44-180aa(SEQ ID NO:7) | 2.2235 | 2.2646 |
| 181-247aa(SEQ ID NO:4) | 0.0114 | 0.0129 |
| 248-364aa(SEQ ID NO:5) | 0.0098 | 0.0104 |
| 365-419aa(SEQ ID NO:6) | 0.0095 | 0.0121 |
| 44-84aa(SEQ ID NO:8) | 2.231 | 2.052 |
| 58-69aa(SEQ ID NO:9) | 2.155 | 2.112 |
以上结果表明，14Q11、19L1两株抗体识别结合突变抗原的44-180aa或44-84aa或58-69aa。
实施例4抗体配对以鉴定突变型抗原
以2019-nCoV野生型N蛋白重组抗原作为免疫原筛选得到结合不同片段的N抗体，参见实施例3鉴定抗体结合片段，得到如下抗体：例如3B8及6D9结合1-43aa，7R1及5S7结合85-95aa，6I3及5C3结合44-180aa，1B5及2F4结合248-364aa；以上抗体均可购自菲鹏生物。
1、新冠N抗体标记：取5ml浓度为4/万的胶体金，加入30-40ul 0.2M K2CO3，搅拌5min，加入新冠N标记抗体(所加抗体体积＝50μg/抗体浓度)，搅拌5min，再加入50ul 10％BSA封闭终止标记；离心10000rpm，7min，去上清，沉淀用金子复溶液复溶，最后用金子复溶液定容到0.5ml(即1/10胶体金溶液体积)。
2、配制金子工作液：用金子复溶液将新冠N标记抗体浓缩金以20％的稀释比例配制成金子工作液，铺于玻璃纤维上。
3、制备干燥好的金子：将铺好的金子放入冻干机冻干(1-2h)或者放37℃干燥房干燥过夜。
4、新冠N抗体包被：将硝酸纤维素膜与PVC底板组装好备用；将结合野生型N蛋白重组抗原的抗体例如3B8、7R1、6I3，或者1B5稀释至1.0-1.5mg/ml，用喷金画膜仪在NC膜上均匀地划T1线；再将筛选得到的特异性结合突变型抗原的14Q11，或者19L1抗体稀释至1.0-1.5mg/ml，用喷金画膜仪在NC膜上均匀地划T2线；放37℃恒温箱60min。
5、制备金标条：用切条机将金标条按需要的宽度切条，组装后加样进行检测。
6、检测
(1)质控品：携带以下位点的突变型N蛋白全长抗原，使用PBS稀释到不同浓度进行抗体配对试验；
(2)检测方法：根据色卡比对，肉眼判读显色读值。
7、结果：
表3-1以7R1为标记抗体检测携带D63G+R203M+D377Y的抗原
表3-2以7R1为标记抗体检测携带D63G+R203M+G215C+D377Y的抗原
表3-3以5S7为标记抗体检测携带D63G，R203K,G204R(即Gx-nCoVN抗原)
表3-4以3B8为标记抗体检测携带D63G，R203K,G204R(即Gx-nCoVN抗原)
表3-5以6I3为标记抗体检测携带D63G，R203K,G204R(即Gx-nCoVN抗原)
表3-6以2F4为标记抗体检测携带D63G，R203K,G204R(即Gx-nCoVN抗原)
表3-1、3-2、3-3、3-4、3-5、3-6中，字母C后的数字代表显色，数字越大，显色越弱(活性越低)。
当待测样品中含N蛋白携带D63G位点突变的突变型抗原时，T1线、T2线均显色；以下试验当待测样品中不含该类型突变抗原时的情况。
表4-1以7R1为标记抗体检测携带D377Y的抗原
表4-2以7R1为标记抗体检测携带R203K+G204R+G212V的抗原
表4-3以7R1为标记抗体检测野生型抗原(N hCoV-19/Wuhan/WIV04/2019)
表4-1、4-2、4-3中，字母B代表不显色(未检出)，字母C后的数字代表显色，数字越大，显色越弱(活性越低)。
利用SEQ ID NO:8或SEQ ID NO:9作为免疫原中的抗原性部分，免疫获得的抗体，均能结合SEQ ID NO:8或SEQ ID NO:9，这些抗体同样能用于鉴定携带D63G突变的抗原。
上述实施例为本发明较佳的实施方式，但本发明的实施方式并不受上述实施例的限制，其他的任何未背离本发明的精神实质与原理下所作的改变、修饰、替代、组合、简化，均应为等效的置换方式，都包含在本发明的保护范围之内。
序列表如下：
SEQ ID NO:1
MSDNGPQNQRNAPRITFGGPSDSTGSNQNGERSGARSKQRRPQGLPNNTASWFTALTQHGKEGLKFPRGQGVPINTNSSPDDQIGYYRRATRRIRGGDGKMKDLSPRWYFYYLGTGPEAGLPYGANKDGIIWVATEGALNTPKDHIGTRNPANNAAIVLQLPQGTTLPKGFYAEGSRGGSQASSRSSSRSRNSSRNSTPGSSKRTSPARMAGNGGDAALALLLLDRLNQLESKMSGKGQQQQGQTVTKKSAAEASKKPRQKRTATKAYNVTQAFGRRGPEQTQGNFGDQELIRQGTDYKHWPQIAQFAPSASAFFGMSRIGMEVTPSGTWLTYTGAIKLDDKDPNFKDQVILLNKHIDAYKTFPPTEPKKDKKKKADETQALPQRQKKQQTVTLLPAADLDDFSKQLQQSMSSADSTQA
SEQ ID NO:2
MSDNGPQNQRNAPRITFGGPSDSTGSNQNGERSGARSKQRRPQ
SEQ ID NO:3
GLPNNTASWFTALTQHGKEDLKFPRGQGVPINTNSSPDDQIGYYRRATRRIRGGDGKMKDLSPRWYFYYLGTGPEAGLPYGANKDGIIWVATEGALNTPKDHIGTRNPANNAAIVLQLPQGTTLPKGFYAEGSRGGS
SEQ ID NO:4
QASSRSSSRSRNSSRNSTPGSSKRTSPARMAGNGGDAALALLLLDRLNQLESKMSGKGQQQQGQTVT
SEQ ID NO:5
KKSAAEASKKPRQKRTATKAYNVTQAFGRRGPEQTQGNFGDQELIRQGTDYKHWPQIAQFAPSASAFFGMSRIGMEVTPSGTWLTYTGAIKLDDKDPNFKDQVILLNKHIDAYKTFP
SEQ ID NO:6
PTEPKKDKKKKADETQALPQRQKKQQTVTLLPAADLDDFSKQLQQSMSSADSTQA
SEQ ID NO:7
GLPNNTASWFTALTQHGKEGLKFPRGQGVPINTNSSPDDQIGYYRRATRRIRGGDGKMKDLSPRWYFYYLGTGPEAGLPYGANKDGIIWVATEGALNTPKDHIGTRNPANNAAIVLQLPQGTTLPKGFYAEGSRGGS
SEQ ID NO:8
GLPNNTASWFTALTQHGKEGLKFPRGQGVPINTNSSPDDQI
SEQ ID NO:9
QHGKEGLKFPRG
SEQ ID NO:10
GYYRRATRRIR
SEQUENCE LISTING
<110> 广东菲鹏生物有限公司
菲鹏生物股份有限公司
<120> 一种鉴定或鉴别新冠突变型抗原的抗体、试剂及方法
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Gly Tyr Tyr Arg Arg Ala Thr Arg Arg Ile Arg
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Claims (12)
1.一种多肽，其特征在于，所述多肽包含SEQ ID NO:9所示的新冠突变型抗原的N蛋白第58-69位氨基酸片段。
2.一种多肽，其特征在于，所述多肽包含SEQ ID NO:8所示的新冠突变型抗原的N蛋白第44-84位氨基酸片段。
3.一种多肽，其特征在于，所述多肽包含SEQ ID NO:7所示的新冠突变型抗原的N蛋白第44-180位氨基酸片段。
4.一种免疫原，其特征在于，所述免疫原包含权利要求1-3任一项所述的多肽。
5.一种杂交瘤细胞，其特征在于，所述杂交瘤细胞由权利要求4所述的免疫原免疫得到的B淋巴细胞与骨髓瘤细胞融合得到。
6.一种抗体，其特征在于，所述抗体结合权利要求1-3任一项所述的多肽；
可选地，所述抗体不结合新冠病毒N蛋白第63位未突变的抗原。
7.一种抗体组合，其特征在于，所述抗体组合包含抗体1和抗体2，所述抗体1为权利要求6所述的抗体，所述抗体2结合新冠病毒N蛋白第1-43、85-95、44-180或248-364位氨基酸片段；
优选地，所述抗体2结合新冠病毒N蛋白第85-95位氨基酸片段；
可选地，所述抗体组合用于鉴定新冠突变型抗原，所述突变型抗原包含新冠病毒N蛋白第63位突变为非天冬氨酸的其它氨基酸。
8.权利要求7所述的抗体组合，其特征在于，所述抗体组合可以进一步包含抗体3，所述抗体3结合新冠病毒N蛋白第1-43、85-95、44-180或248-364位氨基酸片段；
可选地，当抗体2结合新冠病毒N蛋白第44-180位氨基酸片段时，抗体3也可以是结合新冠病毒N蛋白第44-180位氨基酸片段的抗体；
可选地，当抗体2为结合1-43、85-95或248-364位氨基酸片段的抗体时，所述抗体3与抗体2的结合片段不同。
9.一种鉴定新冠突变型抗原的检测试剂，其特征在于，所述试剂包含权利要求6所述的抗体或权利要求7或8所述的抗体组合。
10.一种鉴别新冠突变型抗原的免疫层析试纸，其特征在于，所述免疫层析试纸包括底板、样品垫、结合垫、硝酸纤维素膜和吸水垫，所述硝酸纤维素膜上设置有检测线1和检测线2，所述结合垫上设置有抗体2，所述检测线1上包被抗体1、所述检测线2上包被抗体3，其中抗体1，抗体2和抗体3独立地如权利要求7或8所定义，可选地，所述硝酸纤维素膜上还设置有质控线。
11.一种鉴别新冠突变型抗原的免疫层析试纸，其特征在于，所述免疫层析试纸包括底板、样品垫、结合垫、硝酸纤维素膜和吸水垫，所述硝酸纤维素膜上设置检测线1和检测线2，所述样品垫上设置有生物素化的抗体1，所述结合垫上设置有抗体2，所述检测线1上包被亲和素，所述检测线2上包被抗体3，其中抗体1，抗体2和抗体3独立地如权利要求7或8所定义，可选地，所述硝酸纤维素膜上还设置有质控线。
12.一种鉴别新冠突变型抗原的方法，其特征在于，所述方法包括使权利要求9所述的检测试剂或权利要求10或11所述的免疫层析试纸，与待测样品接触，
可选地，当检测线1和检测线2同时显色，则判定为样品中包含新冠病毒N蛋白第63位突变的抗原；当检测线2显色，检测线1不显色时，则判定为样品中包含新冠病毒N蛋白第63位未突变的抗原。
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