Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
J Med Virol. 2023 Jan;95(1):e28207. doi: 10.1002/jmv.28207. Epub 2022 Oct 19.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) have prolonged coronavirus disease 2019 (COVID-19) pandemic by escaping pre-existing immunity acquired by natural infection or vaccination. Elucidation of VOCs' mutation trends and evasion of neutralization is required to update current control measures. Mutations and the prevalence of VOCs were analyzed in the global immunization coverage rate context. Lentivirus-based pseudovirus neutralization analysis platforms for SARS-CoV-2 prototype strain (PS) and VOCs, containing Alpha, Beta, Gamma, Delta, and Omicron, were constructed based on the spike protein of each variant and HEK 293T cell line expressing the human angiotensin-converting enzyme 2 (hACE2) receptor on the surface, and an enhanced green fluorescent protein reporter. Serum samples from 65 convalescent individuals and 20 WIBP-CorV vaccine recipients and four therapeutic monoclonal antibodies (mAbs) namely imdevimab, casirivimab, bamlanivimab, and etesevimab were used to evaluate the neutralization potency against the variants. Pseudovirus-based neutralization assay platforms for PS and VOCs were established, and multiplicity of infection (MOI) was the key factor influencing the assay result. Compared to PS, VOCs may enhance the infectivity of hACE2-293T cells. Except for Alpha, other VOCs escaped neutralization to varying degrees. Attributed to favorable and emerging mutations, the current pandemic Omicron variant of all VOCs demonstrated the most significant neutralization-escaping ability to the sera and mAbs. Compared with the PS pseudovirus, Omicron had 15.7- and 3.71-fold decreases in the NT50 value (the highest serum dilution corresponding to a neutralization rate of 50%); and correspondingly, 90% and 43% of immunization or convalescent serum samples lost their neutralizing activity against the Omicron variant, respectively. Therefore, SARS-CoV-2 has evolved persistently with a strong ability to escape neutralization and prevailing against the established immune barrier. Our findings provide important clues to controlling the COVID-19 pandemic caused by new variants.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）的关切变异株（VOCs）通过逃避自然感染或接种疫苗获得的现有免疫力，延长了 2019 年冠状病毒病（COVID-19）大流行。阐明 VOCs 的突变趋势和中和逃逸对于更新当前的控制措施是必要的。在全球免疫覆盖率的背景下分析了 VOCs 的突变和流行情况。基于每个变体的刺突蛋白和在表面表达人血管紧张素转换酶 2（hACE2）受体的 HEK 293T 细胞系，构建了针对 SARS-CoV-2 原型株（PS）和包含 Alpha、Beta、Gamma、Delta 和 Omicron 的 VOCs 的基于慢病毒的假病毒中和分析平台，并使用增强型绿色荧光蛋白报告基因。使用来自 65 名恢复期个体和 20 名 WIBP-CorV 疫苗接种者以及四种治疗性单克隆抗体（mAbs）即 imdevimab、casirivimab、bamlanivimab 和 etesevimab 的血清样本评估对变体的中和效力。建立了针对 PS 和 VOCs 的假病毒中和分析平台，感染复数（MOI）是影响分析结果的关键因素。与 PS 相比，VOCs 可能会增强 hACE2-293T 细胞的感染力。除了 Alpha 之外，其他 VOCs 都不同程度地逃避了中和。由于有利和新兴的突变，当前流行的所有 VOCs 的 Omicron 变体对血清和 mAbs 表现出最强的中和逃逸能力。与 PS 假病毒相比，Omicron 的 NT50 值降低了 15.7 倍和 3.71 倍（对应于中和率为 50%的最高血清稀释度）；相应地，90%和 43%的免疫或恢复期血清样本失去了对 Omicron 变体的中和活性。因此，SARS-CoV-2 持续进化，具有很强的中和逃逸能力，并战胜了现有的免疫屏障。我们的发现为控制由新变体引起的 COVID-19 大流行提供了重要线索。
