新冠病毒奥密克戎株感染前后血浆中的抗体变化与分布  

Changes and distribution of antibodies in plasma before and after infection of SARS-CoV-2 Omicron strain

作　　者：周志军 岳胜兰 彭焱 刘俊 邬云芬 邓琨 张云 李娟 陈克金 李策生 曾双迎 胡勇 张金 ZHOU Zhijun;YUE Shenglan;PENG Yan;LIU Jun;WU Yunfen;DENG Kun;ZHANG Yun;LI Juan;CHEN Kejin;LI Cesheng;ZENG Shuangying;HU Yong;ZHANG Jin(Sinopharm Wuhan Plasma-derived Biotherapies Co.,Ltd..,Wuhan 430207,China)

机构地区：[1]国药集团武汉血液制品有限公司,湖北武汉430207

出　　处：《中国输血杂志》2023年第7期578-583,共6页Chinese Journal of Blood Transfusion

基　　金：国家科技部重点专项(2020YFC0841800)。

摘　　要：目的通过ELISA和假病毒中和实验检测奥密克戎株感染前后代表性混合血浆的SARS-CoV-2-IgG水平及针对不同病毒株的中和抗体,了解抗体变化规律及中和抗体分布,确定能用于新冠特免(静脉注射COVID-19人免疫球蛋白)制备的血浆最佳采集时间段。方法建立SARS-CoV-2-IgG的ELISA定量检测方法并进行线性范围、准确度和精密度验证;检测25名献浆者奥密克戎感染后20~40 d的单人份康复期血浆SARS-CoV-2-IgG效价,按照效价结果制备了2组混合血浆小样WP1(1000~2000 EIU/mL)和WP2(2000~4000 EIU/mL),并检测其不同病毒株(原型株、BA.1、BA.2、BA.4/5、BF.7、BQ.1.1)假病毒中和效价,确定不同病毒株中和抗体的反应性分布。检测公司下属14个浆站采集的奥密克戎株感染前后的代表性混浆的SARS-CoV-2-IgG效价,包括2022年12月—2023年5月不同浆站不同时间段采集的奥密克戎康复者血浆(OP)和2022年3—12月采集的奥密克戎感染前的正常合并血浆(VN),根据结果分析献浆者感染奥密克戎株前后SARS-CoV-2-IgG差异及随时间变化规律。结果以内控参考品B2为标准品(效价100 EIU/mL),SARS-CoV-2-IgG的线性范围在6.25~200 EIU/mL,批内准确度在81.793%~106.985%之间,批内精密度在1.100%~13.000%之间,批内总误差在2.988%~22.679%;批间准确度在90.788%~96.893%之间,批间精密度在4.870%~6.272%之间,批间总误差在9.192%~15.399%。假病毒中和抗体的结果显示,WP系列混浆中和抗体效价排序为原型株>BA.2>BA.4/5>BF.7≈BQ.1.1>BA.1,WP1和WP2两者各项检测结果的相关性高(Pearson r=0.9311,P=0.0023),说明奥密克戎感染后康复期血浆中不同病毒株中和抗体效价分布基本稳定。与奥密克戎大规模感染前康复期血浆G128相比,血浆中奥密克戎株的抗体效价明显提高,其中BA.2抗体与原型株抗体的比例由感染前的26.9%上升到感染后的82.6%~87.5%。奥密克戎感染前VN系列检测结果<100 EIU/mL,奥密克戎感染后Objective To determine the best collection time period of plasma which can be used for human COVID-19 immunoglobulin for intravenous injection through SARS-CoV-2-IgG change and neutralizing antibody distribution against different virus strain in representative mixed plasma before and after Omicron strain infection by ELISA and pseudovirus neutralization test.Methods An ELISA method for quantitative detection of SARS-CoV-2-IgG was established and its linear range,accuracy and precision was verified.SARS-CoV-2-IgG potency was detected in 25 convalescent plasma which were collected 20-40 days after confirmed Omicron infection,two groups of mixed plasma samples WP1 and WP2 were prepared according to the SARS-CoV-2-IgG results,and pseudovirus neutralization experiments with different virus strain(prototype strain,BA.1,BA.2,BA.4/5,BF.7,BQ.1.1)were carried out to determine the distribution of neutralizing antibodies against different virus strain.SARS-CoV-2-IgG potency of representative mixed plasma collected from 14 plasma stations subordinate to the company before and after Omicron strain infection was detected,including Omicron convalescent plasma(OP)collected from different plasma stations from December 2022 to May 2023 and normal pool plasma(VN)feed in March 2023 which collected from March 2022 to December 2022.According to the results,the difference and the change rule with time of SARS-CoV-2-IgG before and after Omicron strain infection were analyzed.Results The linearity of SARS-CoV-2-IgG ranged from 6.25 to 200 EIU/mL,the accuracy in-batch ranged from 81.793%to 106.985%,the precision in-batch ranged from 1.100%to 13.000%,and the total error in-batch ranged from 2.988%to 22.679%.The accuracy between batches ranged from 90.788%to 96.893%,the precision between batches ranged from 4.870%to 6.272%,and the total error between batches ranged from 9.192%to 15.399%.The results of pseudovirus neutralizing antibody showed that the potency of different virus strain neutralizing antibodies were in the order of prototype str

关 键 词：新型冠状病毒奥密克戎株 SARS-CoV-2-IgG效价 中和抗体效价 抗体变化和分布 

分 类 号：R457.11[医药卫生—治疗学] R511[医药卫生—临床医学]