Windsor William Jonathan, Roell Yannik, Tucker Heidi, Cheng Chi-An, Suliman Sara, Peek Laura J, Pestano Gary A, Lee William T, Zeichhardt Heinz, Lamb Molly M, Kammel Martin, Wang Hui, Kedl Ross, Rester Cody, Morrison Thomas E, Davenport Bennet J, Carson Kyle, Yates Jennifer, Howard Kelly, Kulas Karen, Walt David R, Dafni Aner, Taylor Daniel, Chu May
Colorado School of Public Health, Center for Global Health, Aurora, CO, United States.
Division of Infectious Diseases, New York State Department of Health, Wadsworth Center, Albany, NY, United States.
Front Microbiol. 2022 May 30;13:893801. doi: 10.3389/fmicb.2022.893801. eCollection 2022.
There is an urgent need for harmonization between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serology platforms and assays prior to defining appropriate correlates of protection and as well inform the development of new rapid diagnostic tests that can be used for serosurveillance as new variants of concern (VOC) emerge. We compared multiple SARS-CoV-2 serology reference materials to the WHO International Standard (WHO IS) to determine their utility as secondary standards, using an international network of laboratories with high-throughput quantitative serology assays. This enabled the comparison of quantitative results between multiple serology platforms.
Between April and December 2020, 13 well-characterized and validated SARS-CoV-2 serology reference materials were recruited from six different providers to qualify as secondary standards to the WHO IS. All the samples were tested in parallel with the National Institute for Biological Standards and Control (NIBSC) 20/136 and parallel-line assays were used to calculate the relevant potency and binding antibody units.
All the samples saw varying levels of concordance between diagnostic methods at specific antigen-antibody combinations. Seven of the 12 candidate materials had high concordance for the spike-immunoglobulin G (IgG) analyte [percent coefficient of variation (%CV) between 5 and 44%].
Despite some concordance between laboratories, qualification of secondary materials to the WHO IS using arbitrary international units or binding antibody units per milliliter (BAU/ml) does not provide any benefit to the reference materials overall, due to the lack of consistent agreeable international unit (IU) or BAU/ml conversions between laboratories. Secondary standards should be qualified to well-characterized reference materials, such as the WHO IS, using serology assays that are similar to the ones used for the original characterization of the WHO IS.
在确定合适的保护相关指标之前，以及随着新的关注变异株（VOC）出现为血清学监测开发可使用的新型快速诊断测试提供信息方面，迫切需要使严重急性呼吸综合征冠状病毒2（SARS-CoV-2）血清学平台和检测方法协调一致。我们使用具有高通量定量血清学检测的国际实验室网络，将多种SARS-CoV-2血清学参考物质与世界卫生组织国际标准（WHO IS）进行比较，以确定它们作为二级标准的效用。这使得能够比较多个血清学平台之间的定量结果。
2020年4月至12月期间，从六个不同供应商处收集了13种特征明确且经过验证的SARS-CoV-2血清学参考物质，以使其有资格作为WHO IS的二级标准。所有样本均与国家生物标准与控制研究所（NIBSC）20/136并行检测，并使用平行线检测法计算相关效价和结合抗体单位。
在特定抗原-抗体组合下，所有样本在诊断方法之间的一致性水平各不相同。12种候选物质中有7种在刺突免疫球蛋白G（IgG）分析物上具有高度一致性[变异系数百分比（%CV）在5%至44%之间]。
尽管实验室之间存在一定的一致性，但由于实验室之间缺乏一致认可的国际单位（IU）或每毫升结合抗体单位（BAU/ml）转换，使用任意国际单位或每毫升BAU对WHO IS的二级物质进行鉴定并不能给参考物质整体带来任何益处。二级标准应使用与用于WHO IS原始鉴定的检测方法相似的血清学检测方法，根据特征明确的参考物质（如WHO IS）进行鉴定。
