CN115677851A - 一种免疫阻断抗体或其抗原结合片段及其应用 - Google Patents
一种免疫阻断抗体或其抗原结合片段及其应用 Download PDFInfo
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- CN115677851A CN115677851A CN202110861239.8A CN202110861239A CN115677851A CN 115677851 A CN115677851 A CN 115677851A CN 202110861239 A CN202110861239 A CN 202110861239A CN 115677851 A CN115677851 A CN 115677851A
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Images
Abstract
本发明涉及一种免疫阻断抗体或其抗原结合片段及其应用。本发明提供的抗体的稳定性好，对内源性干扰有显著的阻断效果，能够显著降低甚至消除内源性干扰，进而提高免疫检测的准确度，方便高效，该抗体或其抗原结合片段、及其相关的核酸、载体或细胞能够广泛应用于作为或制备免疫阻断剂，以及制备免疫检测试剂或试剂盒。
Description
技术领域
本发明属于抗体技术领域。更具体地，涉及一种免疫阻断抗体或其抗原结合片段及其应用。
背景技术
基于抗原抗体反应的免疫检测方法应用广泛，根据抗体标记物分为不同的检测方法，如：酶联免疫、放射免疫、化学发光等。在临床应用中，免疫检测结果的准确性往往在不同程度上受病人血清中干扰物的影响，从而导致错误的检测结果。血清中的干扰物可分为内源性干扰和外源性干扰，外源性干扰包括溶血、样本染菌、血液凝固不彻底、样本的稳定性与保存条件等；内源性干扰包括类风湿因子(RF)、嗜异性抗体(HA)、自身抗体、补体、黄疸、高脂等；其中，RF、HA是重要的干扰因素。研究证实，约3％-15％健康人群的体内含有内源性干扰因素，10％以上(30％-40％)的病人体内存在HA干扰，10％-40％的人群中存在HAMA干扰。在内源性干扰中，以RF、HA最为常见。因此，研究、发展降低甚至消除RF干扰、HA干扰的有效手段，是保证医学免疫检验结果可靠性、保障医患利益的重要课题。
针对消除免疫诊断中的RF干扰、HA干扰，最简单、最有效的方法就是在检测系统中添加阻断剂，直接阻断干扰物质与检测系统中抗体或抗原的结合。阻断剂是一种生物制剂，加入免疫检验体系中，可与内源性抗体反应，从而有效防止非分析物介导的抗体桥连。阻断剂可分为被动阻断剂和主动阻断剂。
被动阻断剂是使用非特异性物质(如小鼠IgG，小鼠血清，非特异性单克隆抗体，聚集的IgG等)来阻断人异源抗体的结合，如商品化试剂中MAK33、MAB33等。这类试剂用途有限，只能阻断一种人抗特定动物抗体的活性试剂(如人类抗鼠抗体)，阻断效果依赖于人异源抗体的亲和力，人异源抗体的亲和力通常在105-106的K值范围内。因此，被动阻断剂在使用过程中，往往通过高浓度添加来降低干扰。此外，嗜性干扰涉及许多成分，阻断不同种类的异嗜性抗体时需要使用不同的被动阻断剂。
目前，用于诊断的免疫检测原料还是以鼠McAb为主，所以大多数阻断剂还是鼠抗体，主动阻断剂为鼠抗人免疫球蛋白抗体，被动阻断剂为针对其他蛋白的鼠抗体。市场上的阻断剂产品虽然较多，但是均存在一定的性能缺陷，加之阻断剂本身用量非常大，而主流的阻断剂进口居多、价格偏高，所以市场亟需性能更优、成本更低的阻断剂。
发明内容
本发明要解决的技术问题是克服现有免疫阻断剂成本高、性能不好的缺陷和不足，提供一种免疫阻断抗体或其抗原结合片段及其应用，所述免疫阻断抗体的稳定性好，成本低，将所述抗体加入免疫检测系统中能够降低甚至消除内源性干扰，且其阻断效果显著好于市场阻断剂原料，该抗体可作为或制备免疫阻断剂，以及制备免疫检测试剂或试剂盒。
本发明的目的是提供一种抗体或其抗原结合片段，所述抗体含有以下CDRs：
氨基酸序列如SEQ ID NO.1所示的HCDR1，氨基酸序列如SEQ ID NO.2所示的HCDR2，氨基酸序列如SEQ ID NO.3所示的HCDR3；氨基酸序列如SEQ ID NO.4所示的LCDR1，氨基酸序列如SEQ ID NO.5所示的LCDR2，氨基酸序列如SEQ ID NO.6所示的LCDR3。
本发明的另一目的是提供所述抗体或其抗原结合片段相关的核酸、载体或细胞。
本发明还提供了所述抗体或其抗原结合片段，及其相关的核酸、载体或细胞在免疫检测中的应用。
本发明还提供了所述抗体或其抗原结合片段，及其相关的核酸、载体或细胞在作为/制备免疫阻断剂中的应用。
本发明还提供了一种免疫阻断剂，含有所述抗体或其抗原结合片段、所述载体、所述核酸或所述细胞。
本发明还提供了一种免疫诊断试剂/试剂盒，其包含所述免疫阻断剂。
本发明还提供了一种降低/消除内源性干扰的方法，在免疫检测系统中添加所述免疫阻断剂。
附图说明
图1是6F13RMb1抗体的还原性SDS-PAGE结果。
具体实施方式
以下结合具体实施例来进一步说明本发明，但实施例并不对本发明做任何形式的限定。除非特别说明，本发明采用的试剂、方法和设备为本技术领域常规试剂、方法和设备。
除非特别说明，以下实施例所用试剂和材料均为市购。
本发明涉及一种抗体或其抗原结合片段，所述抗体含有以下CDRs：
氨基酸序列如SEQ ID NO.1所示的HCDR1，氨基酸序列如SEQ ID NO.2所示的HCDR2，氨基酸序列如SEQ ID NO.3所示的HCDR3；氨基酸序列如SEQ ID NO.4所示的LCDR1，氨基酸序列如SEQ ID NO.5所示的LCDR2，氨基酸序列如SEQ ID NO.6所示的LCDR3。
所述抗体或其抗原结合片段对假阳样本和RF样本有显著的阻断效果，且其阻断效果甚至好于市场阻断剂原料，能够降低甚至消除内源性干扰。
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。术语“抗原结合片段”是包含抗体CDR的一部分或全部的物质，其缺乏至少一些存在于全长链中的氨基酸但仍能够特异性结合至抗原。此类片段具生物活性，因为其结合至抗原，且可与其他抗原结合分子(包括完整抗体)竞争结合至给定表位。此类片段选自Fab(由完整的轻链和Fd构成)，Fv(由VH和VL构成)，ScFv(单链抗体，VH和VL之间由一连接肽连接而成)或单域抗体(仅由VH组成)。此类片段可通过重组核酸技术产生，或可通过抗原结合分子(包括完整抗体)的酶裂解或化学裂解产生。在本发明具体实施方式中，所述抗体的抗原结合片段能够显著阻断假阳样本和RF样本，降低甚至消除内源性干扰。
在本发明中，术语“互补性决定区”、“CDR”或“CDRs”是指免疫球蛋白的重链和轻链的高度可变区，指包含一种或多种或者甚至全部的对抗体或其抗原结合片段与其识别的抗原或表位的结合亲和力起作用的主要氨基酸残基的区域。在本发明具体实施方式中，CDRs是指所述抗体的重链和轻链的高度可变区。
在本发明中，重链互补决定区用HCDR表示，其包括HCDR1、HCDR2和HCDR3；轻链互补决定区用LCDR表示，其包括LCDR1、LCDR2和LCDR3。本领域常用的CDR标示方法包括：Kabat编号方案、Chothia和Lesk编号方案以及1997年Lefranc等人为免疫球蛋白超家族的所有蛋白质序列引入的新的标准化编号系统。Kabat等人是第一个为免疫球蛋白可变区提出标准化编号方案的人。在过去的几十年中，序列的积累导致了KABATMAN数据库的创建，Kabat编号方案通常被认为是编号抗体残基广泛采用的标准。本发明采用Kabat注释标准标示CDR区，但其他方法标示的CDR区也属于本发明的保护范围。
在本发明中，“框架区”或“FR”区包括重链框架区和轻链框架区，是指抗体重链可变区和轻链可变区中除CDR之外的区域；其中，重链框架区可以被进一步细分成被CDR分隔开的毗邻区域，包含HFR1、HFR2、HFR3和HFR4框架区；轻链框架区可以被进一步细分成被CDR分隔开的毗邻区域，包含HFR1、HFR2、HFR3和HFR4框架区。
在本发明中，重链可变区由以下编号的CDR与FR按如下组合排列连接获得：HFR1-HCDR1-HFR2-HCDR2-HFR3-HCDR3-HFR4；轻链可变区由以下编号的CDR与FR按如下组合排列连接获得：LFR1-LCDR1-LFR2-LCDR2-LFR3-LCDR3-LFR4。
在一些实施方式中，所述抗体还含有重链框架区和轻链框架区的至少之一；所述重链框架区包含氨基酸序列依次如SEQ ID NO:11～14所示的HFR1、HFR2、HFR3和HFR4框架区，所述轻链框架区包含氨基酸序列依次如SEQ ID NO:15～18所示的LFR1、LFR2、LFR3和LFR4框架区。
在一些实施方式中，所述抗体还含有重链可变区和轻链可变区的至少之一；所述抗体的重链可变区的氨基酸序列如SEQ ID NO:7所示，所述抗体的轻链可变区的氨基酸序列如SEQ ID NO:8所示。
在一些实施方式中，所述抗体还含有重链恒定区和轻链恒定区；所述重链恒定区为IgG1、IgG2、IgG3、IgG4、IgA、IgD、IgE或IgM中的任一种或几种，所述轻链恒定区为κ链或λ链。
在一些实施方式中，所述重链恒定区和轻链恒定区的种属来源为牛、马、乳牛、猪、绵羊、山羊、大鼠、小鼠、狗、猫、兔、骆驼、驴、鹿、貂、鸡、鸭、鹅、火鸡、斗鸡或人。
在一些实施方式中，所述抗体的重链的氨基酸序列如SEQ ID NO:9所示，所述抗体的轻链的氨基酸序列如SEQ ID NO:10所示。
在一些实施方式中，所述抗原结合片段选自Fab，Fab'，F(ab')2，scFv，Fv，Fd，单链抗体，双价抗体或结构域抗体。
本发明还涉及核酸，所述核酸编码所述抗体或其抗原结合片段。
核酸通常是RNA或DNA，核酸分子可以是单链或双链的。当将核酸与另一个核酸序列置于功能关系中时，核酸是“有效连接的”。例如，如果启动子或增强子影响编码序列的转录，那么启动子或增强子有效地连接至所述编码序列。当其连入载体时采用DNA核酸。
本发明还涉及载体，所述载体含有所述核酸。
本发明还涉及细胞，所述细胞含有所述核酸或所述载体。
所述抗体或其抗原结合片段、所述核酸、所述载体或所述细胞在免疫检测中的应用，及其在作为/制备免疫阻断剂中的应用，都应在本发明的保护范围之内。
本发明还涉及一种免疫阻断剂，含有所述抗体或其抗原结合片段、所述核酸、所述载体或所述细胞。
本发明还涉及一种免疫诊断试剂/试剂盒，其包含所述免疫阻断剂。
在一些实施方式中，所述试剂盒为免疫层析检测试剂盒、酶免检测试剂盒、化学发光试剂盒或免疫比浊检测试剂盒。
在一些实施方式中，所述试剂盒可以包括测试条或测试卡，来自于所述受试者的所述液体样品放置到所述测试条上，或者ELISA测定板，所述ELISA测定板具有其中可放置来自于单个受试者的液体样品的孔。在一些实施方案中，所述试剂盒可以包括配置用于流式细胞仪、生物分析仪、生物传感器中的测试装置。
在一些实施方式中，所述试剂盒中包含的所述免疫阻断剂可为液体溶液形式、附着于固体支持物上的形式、或为干燥粉剂。当免疫阻断剂为一种液体溶液时，该液体溶液可以是水溶液。当免疫阻断剂是附着于固体支持物上的形式时，优选的固体支持物可以是层析介质如薄膜、测试条、塑料珠或平板、或显微镜栽玻片。当免疫阻断剂为一种干燥粉剂时，通过加入适当溶剂可重构粉剂。
本发明还涉及一种降低/消除内源性干扰的方法，在免疫检测系统中添加所述免疫阻断剂。
在本发明具体实施方式中，所述内源性干扰为类风湿因子干扰或嗜异性抗体干扰。
本发明具有以下有益效果：
本发明提供了一种免疫阻断抗体或其抗原结合片段及其应用，与市场阻断剂原料相比，该抗体稳定性好、成本低，对内源性干扰有显著的阻断效果，能够降低甚至消除内源性干扰，进而提高免疫检测的准确度，方便高效；因此，所述抗体或其抗原结合片段、及其相关的核酸、载体或细胞能够广泛应用于免疫检测领域中，作为或制备免疫阻断剂，以及制备免疫检测试剂或试剂盒。
下面将结合实施例对本发明的实施方案进行详细描述。
以下实施例中，rTaq DNA聚合酶购自Takara公司。pMD-18T载体购自Takara公司。限制性内切酶购自Takara公司。MagExtractor-RNA提取试剂盒购自TOYOBO公司。BD SMARTTMRACE cDNAAmplification Kit试剂盒购自Takara公司。质粒提取试剂盒购自天根公司。引物合成和基因测序由Invitrogen公司完成。
实施例1免疫阻断抗体(6F13RMb1抗体)的制备
1、表达质粒构建
(1)6F13RMb1抗体基因制备
从分泌6F13RMb1抗体的杂交瘤细胞株中提取mRNA，通过RT-PCR方法获得DNA产物，该产物用rTaq DNA聚合酶进行加A反应后插入到pMD-18T载体中，转化到DH5α感受态细胞中，长出菌落后分别取重链(Heavy Chain)及轻链(Light Chain)基因克隆各4个克隆送基因测序公司进行测序。
(2)6F13RMb1抗体可变区基因的序列分析
将上述测序得到的基因序列放在IMGT抗体数据库中进行分析，并利用VNTI11.5软件进行分析确定重链和轻链引物对扩增出的基因都是正确的；其中，Light Chain扩增出的基因片段中，轻链可变区(variable region of light chain，VL)基因序列为321bp，属于VkII基因家族，其前方有57bp的前导肽序列；Heavy Chain引物对扩增出的基因片段中，重链可变区(variable region of heavy chain，VH)基因序列为369bp，属于VH1基因家族，其前方有57bp的前导肽序列。
(3)重组抗体表达质粒的构建
pcDNATM 3.4
vector为构建的重组抗体真核表达载体，该表达载体已经引入HindIII、BamHI、EcoRI等多克隆酶切位点，并命名为pcDNA3.4A表达载体，后续简称3.4A表达载体；根据上述pMD-18T载体中抗体可变区基因测序结果，设计6F13RMb1抗体的VL和VH基因特异性引物，两端分别带有HindIII、EcoRI酶切位点和保护碱基，通过PCR扩增方法扩出0.71KB的Light Chain基因片段和1.41kb的Heavy Chain基因片段。
Heavy Chain和Light Chain基因片段分别采用HindIII/EcoRI双酶切，3.4A载体采用HindIII/EcoRI双酶切，将片段和载体纯化回收后Heavy Chain基因和Light Chain基因分别连接3.4A表达载体中，分别得到Heavy Chain和Light Chain的重组表达质粒。
2、稳定细胞株筛选
(1)重组抗体表达质粒瞬时转染CHO细胞，确定表达质粒是否表达鼠抗
质粒用超纯水稀释至40μg/100μL，调节CHO细胞1.43×107cells/mL于离心管中，100μL质粒与700μL细胞混合，转入电转杯，电转，第3、5、7天取样计数，第7天收样检测。
包被液(主要成分为NaHCO3)稀释羊抗鼠IgG至1μg/mL，每孔100μL，4℃过夜；次日，洗涤液(主要成分为Na2HPO4+NaCl)清洗2次，拍干；加入封闭液(20％BSA+80％PBS)，每孔120μL，37℃，1h，拍干；加入稀释后的细胞上清，100μL/孔，37℃，30min(部分上清1h)；洗涤液清洗5次，拍干；加入羊抗鼠IgG-HRP，每孔100μL，37℃，30min；洗涤液清洗5次，拍干；加入50μL/孔显色液A液(主要成分为柠檬酸、醋酸钠、乙酰苯胺和过氧化脲)，加入50μL/孔显色液B液(主要成分为柠檬酸、EDTA·2Na、TMB和浓HCl)，10min；加入终止液(主要成分为EDTA·2Na和浓H2SO4)，50μL/孔；酶标仪上450nm(参考630nm)处读OD值。
结果显示，细胞上清稀释1000倍后反应OD仍大于1.0，未加细胞上清孔反应OD小于0.1，表明质粒瞬转后产生的抗体为鼠IgG抗体。
(2)重组抗体表达质粒线性化
准备下述试剂：Buffer 50μL、DNA 100μg/管、PvuⅠ酶10μL、无菌水补至500μL，37℃水浴酶切过夜；先用等体积酚/氯仿/异戊醇(下层)25:24:1，再用氯仿(水相)依次进行抽提；0.1倍体积(水相)3M醋酸钠和2倍体积乙醇冰上沉淀，70％乙醇漂洗沉淀，去除有机溶剂，待乙醇挥发完全用适量的灭菌水进行复融，最后进行浓度的测定。
(3)重组抗体表达质粒稳定转染，加压筛选稳定细胞株
质粒用超纯水稀释至40μg/100μL，调节CHO细胞1.43×107cells/mL于离心管中，100μL质粒与700μL细胞混合，转入电转杯，电转，次日计数；25μmol/L MSX 96孔加压培养约25天。
显微镜下观察标记长有细胞的克隆孔，并记录汇合度；取培养上清，送样检测；挑选抗体浓度、相对浓度高的细胞株转24孔，3天左右转6孔；3天后保种批培，调整细胞密度0.5×106cells/mL，2.2mL进行批培养，细胞密度0.3×106cells/mL，2mL进行保种；7天6孔批培上清送样检测，挑选抗体浓度及细胞直径较小的细胞株转TPP保种传代。
3、6F13RMb1抗体制备
(1)细胞扩培
细胞复苏之后先在125mL规格的摇瓶中培养，接种体积为30mL，培养基为100％Dynamis培养基，放置于转速120r/min，温度为37℃，二氧化碳为8％的摇床中。培养72h，以50万cells/mL接种密度接种扩培，扩培体积根据生产需求进行计算，培养基为100％Dynamis培养基。之后每72h扩培一次。当细胞量满足生产需求时，严格控制接种密度为50万cells/mL左右进行生产。
(2)摇瓶生产及纯化
摇瓶参数：转速120r/min，温度为37℃，二氧化碳为8％。流加补料：在摇瓶中培养至72h时开始每天补料，HyCloneTM Cell BoostTM Feed 7a每天流加初始培养体积的3％，Feed 7b每天流加量为初始培养体积的千分之一，一直补到第12天(第12天补料)。葡萄糖在第六天补加3g/L。第13天收样。用proteinA亲和层析柱进行亲和纯化，即得到6F13RMb1抗体。取6.6μg 6F13RMb1抗体进行还原性SDS-PAGE。
6F13RMb1抗体的还原性SDS-PAGE结果如图1所示，结果显示两条带，1条Mr为50KD(重链)，另一条Mr为28KD(轻链)。
6F13RMb1抗体的HCDR1的氨基酸序列如SEQ ID NO.1所示，HCDR2的氨基酸序列如SEQ ID NO.2所示，HCDR3的氨基酸序列如SEQ ID NO.3所示；LCDR1的氨基酸序列如SEQ IDNO.4所示，LCDR2的氨基酸序列如SEQ ID NO.5所示，LCDR3的氨基酸序列如SEQ ID NO.6所示；
重链框架区包含氨基酸序列依次如SEQ ID NO:11～14所示的HFR1、HFR2、HFR3和HFR4框架区，轻链框架区包含氨基酸序列依次如SEQ ID NO:15～18所示的LFR1、LFR2、LFR3和LFR4框架区；
重链可变区的氨基酸序列如SEQ ID NO:7所示，轻链可变区的氨基酸序列如SEQID NO:8所示；
重链的氨基酸序列如SEQ ID NO:9所示，轻链的氨基酸序列如SEQ ID NO:10所示。
实施例2免疫阻断抗体的阻断性能测定
1、在CTNI荧光平台验证阻断性能
在CTNI荧光平台配对检测中，实验组用实施例1制备得到的6F13RMb1抗体和市场阻断剂原料分别处理样品垫，空白对照组样品垫不作处理；分别检测样本(L1-L11)。
6F13RMb1抗体在CTNI荧光平台的阻断效果如表1所示，结果显示，实验组对假阳样本有显著的消除作用，且6F13RMb1抗体对假阳样本的阻断效果显著优于市场阻断剂原料。
表1
表1中，T/C值说明：
待测样本加入到检测试剂卡的加样口中，在侧向毛细管作用下，待检样本先经过结合垫，与结合垫上的荧光基团标记抗体发生特异的免疫结合，各自结合形成抗原-抗体荧光复合物，从而被固定在T线中。C线上包被有与游离的荧光基团标记抗体发生反应的物质，当游离的荧光基团标记抗体经过C线时，能够与C线上的物质发生特异的免疫结合，从而被固定在C线中。荧光免疫分析仪检测出的两条带的荧光强度以峰面积体现，并通过仪器自身的计算软件计算T/C值。仪器读值T/C表示T峰面积与C峰面积比值，在质控样本和阳性样本下，T/C越高代表活性越高；在假阳样本下T/C越低，代表阻断效果越好；当T/C值＜0.1时，即判断为阴性样本。
2、在CA242化学发光平台验证阻断性能
在CA242化学发光平台配对检测中，实验组分别将浓度为100μg/mL、30μg/mL、10μg/mL和5μg/mL的实施例1制备得到的6F13RMb1抗体和市场阻断剂原料分别加入到包被体系中，空白对照组包被体系中不加，分别检测RF样本1和RF样本2。
6F13RMb1抗体在CA242化学发光平台的阻断效果如表2所示，结果显示，实验组对RF样本有显著的消除作用，且6F13RMb1抗体在极低剂量情况下(5μg/mL)即可对RF样本有显著好于市场阻断剂原料的阻断效果。
表2
表2中的数值为化学发光免疫分析仪读取的OD值，OD值越低，代表检测信号越弱，说明阻断效果越好。
实施例3免疫阻断抗体的稳定性考核
将实施例1制备得到的6F13RMb1抗体置于4℃(冰箱)、-80℃(冰箱)、37℃(恒温箱)放置21天，取7天、14天、21天样品进行状态观察，并对21天样品进行活性检测(利用酶免检测OD结果考核样品的活性)。
6F13RMb1抗体的稳定性测试结果如表3所示，结果显示，三种考核条件下抗体放置21天均未见明显蛋白状态变化，活性也未随考核温度的升高呈下降趋势，说明本发明制备得到的免疫阻断抗体的稳定高。
表3
| 样品浓度(ng/mL) | 125 | 31.25 | 0 |
| 4℃，21天样品 | 2.251 | 1.969 | 0.037 |
| -80℃，21天样品 | 2.234 | 1.919 | 0.032 |
| 37℃，21天样品 | 2.341 | 1.981 | 0.049 |
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。
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Claims (13)
1.一种抗体或其抗原结合片段，其特征在于，所述抗体含有以下CDRs：
氨基酸序列如SEQ ID NO.1所示的HCDR1，氨基酸序列如SEQ ID NO.2所示的HCDR2，氨基酸序列如SEQ ID NO.3所示的HCDR3；氨基酸序列如SEQ ID NO.4所示的LCDR1，氨基酸序列如SEQ ID NO.5所示的LCDR2，氨基酸序列如SEQ ID NO.6所示的LCDR3。
2.根据权利要求1所述抗体或其抗原结合片段，其特征在于，所述抗体还含有重链框架区和轻链框架区的至少之一；所述重链框架区包含氨基酸序列依次如SEQ ID NO:11～14所示的HFR1、HFR2、HFR3和HFR4框架区，所述轻链框架区包含氨基酸序列依次如SEQ ID NO:15～18所示的LFR1、LFR2、LFR3和LFR4框架区。
3.根据权利要求1所述抗体或其抗原结合片段，其特征在于，所述抗体还含有重链可变区和轻链可变区的至少之一；所述抗体的重链可变区的氨基酸序列如SEQ ID NO:7所示，所述抗体的轻链可变区的氨基酸序列如SEQ ID NO:8所示。
4.根据权利要求1所述抗体或其抗原结合片段，其特征在于，所述抗体还含有重链恒定区和轻链恒定区；所述重链恒定区为IgG1、IgG2、IgG3、IgG4、IgA、IgD、IgE或IgM中的任一种或几种，所述轻链恒定区为κ链或λ链；
可选地，所述重链恒定区和轻链恒定区的种属来源为牛、马、乳牛、猪、绵羊、山羊、大鼠、小鼠、狗、猫、兔、骆驼、驴、鹿、貂、鸡、鸭、鹅、火鸡、斗鸡或人。
5.根据权利要求1所述抗体或其抗原结合片段，其特征在于，所述抗体的重链的氨基酸序列如SEQ ID NO:9所示，所述抗体的轻链的氨基酸序列如SEQ ID NO:10所示。
6.根据权利要求1所述抗体或其抗原结合片段，其特征在于，所述抗原结合片段选自Fab，Fab'，F(ab')2，scFv，Fv，Fd，单链抗体，双价抗体或结构域抗体。
7.核酸，其特征在于，所述核酸编码权利要求1～6任一所述抗体或其抗原结合片段。
8.载体，其特征在于，所述载体含有权利要求7所述核酸。
9.细胞，其特征在于，所述细胞含有权利要求7所述核酸或权利要求8所述载体。
10.权利要求1～6任一所述抗体或其抗原结合片段、权利要求7所述核酸、权利要求8所述载体或权利要求9所述细胞在免疫检测中或作为/制备免疫阻断剂中的应用。
11.一种免疫阻断剂，其特征在于，含有权利要求1～6任一所述抗体或其抗原结合片段、权利要求7所述核酸、权利要求8所述载体或权利要求9所述细胞。
12.一种免疫检测试剂/试剂盒，其特征在于，含有权利要求9所述免疫阻断剂。
13.一种降低/消除内源性干扰的方法，其特征在于，在免疫检测系统中添加权利要求10所述免疫阻断剂。
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