Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.
Immunity. 2021 Sep 14;54(9):2159-2166.e6. doi: 10.1016/j.immuni.2021.08.013. Epub 2021 Aug 17.
The emergence of SARS-CoV-2 antigenic variants with increased transmissibility is a public health threat. Some variants show substantial resistance to neutralization by SARS-CoV-2 infection- or vaccination-induced antibodies. Here, we analyzed receptor binding domain-binding monoclonal antibodies derived from SARS-CoV-2 mRNA vaccine-elicited germinal center B cells for neutralizing activity against the WA1/2020 D614G SARS-CoV-2 strain and variants of concern. Of five monoclonal antibodies that potently neutralized the WA1/2020 D614G strain, all retained neutralizing capacity against the B.1.617.2 variant, four also neutralized the B.1.1.7 variant, and only one, 2C08, also neutralized the B.1.351 and B.1.1.28 variants. 2C08 reduced lung viral load and morbidity in hamsters challenged with the WA1/2020 D614G, B.1.351, or B.1.617.2 strains. Clonal analysis identified 2C08-like public clonotypes among B cells responding to SARS-CoV-2 infection or vaccination in 41 out of 181 individuals. Thus, 2C08-like antibodies can be induced by SARS-CoV-2 vaccines and mitigate resistance by circulating variants of concern.
SARS-CoV-2 抗原变体的出现增加了其传染性，这对公共卫生构成了威胁。一些变体对 SARS-CoV-2 感染或疫苗接种诱导的抗体的中和作用表现出显著的抵抗力。在这里，我们分析了来自 SARS-CoV-2 mRNA 疫苗诱导的生发中心 B 细胞的受体结合域结合的单克隆抗体对 WA1/2020 D614G SARS-CoV-2 株和关注变体的中和活性。在能有效中和 WA1/2020 D614G 株的五种单克隆抗体中，所有抗体都保留了对 B.1.617.2 变体的中和能力，四种抗体也中和了 B.1.1.7 变体，只有一种抗体 2C08 也中和了 B.1.351 和 B.1.1.28 变体。2C08 降低了感染 WA1/2020 D614G、B.1.351 或 B.1.617.2 株的仓鼠的肺部病毒载量和发病率。克隆分析在 181 个人中的 41 个人中发现了与 SARS-CoV-2 感染或接种疫苗后反应的 B 细胞中存在 2C08 样公共克隆型。因此，2C08 样抗体可由 SARS-CoV-2 疫苗诱导，并减轻循环关注变体的耐药性。
