新型冠状病毒Omicron XBB.1.5中和抗体检测方法的建立  

Establishment of neutralizing antibody detection method for SARS⁃CoV⁃2 Omicron XBB.1.5

作　　者：代航 毛群颖[1] 胡春霞 刘建阳 张佳璐 李玉薇 刘明琛 李娜[4] 贺倩 王泽鋆 梁争论[1] 李长贵[1] 徐苗[1] DAI Hang;MAO Qunying;HU Chunxia;LIU Jianyang;ZHANG Jialu;LI Yuwei;LIU Mingchen;LI Na;HE Qian;WANG Zejun;LIANG Zhenglun;LI Changgui;XU Miao(National Institutes for Food and Drug Control,Beijing 102629,China;不详)

机构地区：[1]中国食品药品检定研究院,北京102629 [2]武汉生物制品研究所有限责任公司,湖北武汉430060 [3]北京华夏清医治疗科技有限公司,北京100084 [4]北京民海生物科技有限公司,北京102609

出　　处：《中国生物制品学杂志》2024年第10期1225-1229,1238,共6页Chinese Journal of Biologicals

基　　金：广州国家实验室项目:BA.5大流行后人群免疫水平监测和疫苗免疫策略研究(SRPG23-005)。

摘　　要：目的依据全球最新的分析方法质量源于设计(Analysis Quality by Design,AQbD)和全生命周期理念,建立适用于新型冠状病毒Omicrion XBB.1.5变异株的临床中和抗体和流行病学调查用中和抗体检测方法。方法在已建立的新型冠状病毒原型株中和抗体(CPE法)检测方法的基础上,针对XBB.1.5变异株变更对中和抗体检测方法可能引入的影响因素进行风险评估,对主要风险因素进行条件优化,获得适应XBB.1.5变异株的检测方法,经方法验证明确该方法各项性能指标,并证明方法可满足分析目标概要(Analysis Target Profile,ATP)。结果由XBB.1.5变异株变更引入的主要风险因素为检测细胞、培养基种类和结果判定时间;通过对实验条件优化,最终确定将Vero-E6细胞(DMEM培养基)作为XBB.1.5变异株的最佳培养条件,第5天作为最佳观察时间;经验证得到方法相对准确度和中间精密度的平均相对偏倚为-9.2%~2.9%、几何变异系数(geometric coefficient of variation,GCV)为33.2%~47.1%,满足方法预设ATP,方法误判率低于1.6%。结论依据AQbD和全生命周期的研究理念建立了针对新型冠状病毒XBB.1.5变异株的中和抗体检测方法,经验证该方法满足预设ATP,可用于临床中和抗体和流行病学调查用中和抗体检测。Objective According to the latest global Analysis Quality by Design(AQbD)and whole life cycle concept,a neutralizing antibody detection method for clinical and epidemiological investigations of the SARS-CoV-2 Omicron XBB.1.5.Methods Based on the established neutralizing antibody detection method(CPE method)of SARS-CoV-2 prototype strain,a risk assessment was conducted for the potential impact factors introduced by changes in the XBB.1.5 on the neutralizing antibody detection method.The main risk factors were conditionally optimized to obtain the detection method adapted to the XBB.1.5.The method was validated for the various performance indicators and demonstrated to meet the pre-set Analysis Target Profile(ATP)by method validation.Results The main risk factors introduced by the XBB.1.5 change were the cells,culture media,and the time for result determination.Through optimization of the experimental conditions,the best detection conditions for XBB.1.5 were ultimately determined to be observation on the 5th day,using Vero-E6 cells in DMEM culture medium.It was verified that the method had a relative accuracy and intermediate precision of average relative bias of-9.2%to 2.9%,and a GCV of 33.2%to 47.1%,which met the requirements of ATP.Meanwhile the misjudgment rate of the method was less than 1.6%.Conclusion Based on the AQbD and whole life cycle research concept,a neutralizing antibody detection method for the SARS-CoV-2 XBB.1.5 variant has been established,which was verified to meet the original ATP,and can be used for neutralizing antibody detection in clinical and epidemiological investigations.

关 键 词：新型冠状病毒 Omicron变异株 中和抗体 分析方法质量源于设计 全生命周期 

分 类 号：R392-33[医药卫生—免疫学]