Schmitz Aaron J, Turner Jackson S, Liu Zhuoming, Aziati Ishmael D, Chen Rita E, Joshi Astha, Bricker Traci L, Darling Tamarand L, Adelsberg Daniel C, Alsoussi Wafaa B, Case James Brett, Lei Tingting, Thapa Mahima, Amanat Fatima, O'Halloran Jane A, Shi Pei-Yong, Presti Rachel M, Krammer Florian, Bajic Goran, Whelan Sean P J, Diamond Michael S, Boon Adrianus C M, Ellebedy Ali H
Department of Pathology and Immunology, Washington University School of Medicine; St. Louis, USA.
Molecular Microbiology, Washington University School of Medicine; St. Louis, USA.
bioRxiv. 2021 Mar 24:2021.03.24.436864. doi: 10.1101/2021.03.24.436864.
The emergence of antigenically distinct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with increased transmissibility is a public health threat. Some of these variants show substantial resistance to neutralization by SARS-CoV-2 infection- or vaccination-induced antibodies, which principally target the receptor binding domain (RBD) on the virus spike glycoprotein. Here, we describe 2C08, a SARS-CoV-2 mRNA vaccine-induced germinal center B cell-derived human monoclonal antibody that binds to the receptor binding motif within the RBD. 2C08 broadly neutralizes SARS-CoV-2 variants with remarkable potency and reduces lung inflammation, viral load, and morbidity in hamsters challenged with either an ancestral SARS-CoV-2 strain or a recent variant of concern. Clonal analysis identified 2C08-like public clonotypes among B cell clones responding to SARS-CoV-2 infection or vaccination in at least 20 out of 78 individuals. Thus, 2C08-like antibodies can be readily induced by SARS-CoV-2 vaccines and mitigate resistance by circulating variants of concern.
Protection against SARS-CoV-2 variants by a potently neutralizing vaccine-induced human monoclonal antibody.
具有更高传播性的抗原性不同的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）变体的出现是一种公共卫生威胁。其中一些变体对SARS-CoV-2感染或疫苗诱导的抗体的中和作用表现出显著抗性，这些抗体主要靶向病毒刺突糖蛋白上的受体结合域（RBD）。在此，我们描述了2C08，一种源自SARS-CoV-2 mRNA疫苗诱导的生发中心B细胞的人单克隆抗体，它与RBD内的受体结合基序结合。2C08以显著效力广泛中和SARS-CoV-2变体，并减轻用原始SARS-CoV-2毒株或最近关注的变体攻击的仓鼠的肺部炎症、病毒载量和发病率。克隆分析在78名个体中至少20人的对SARS-CoV-2感染或疫苗接种有反应的B细胞克隆中鉴定出2C08样公共克隆型。因此，SARS-CoV-2疫苗可轻易诱导出2C08样抗体，并减轻相关循环变体的抗性。
一种强效中和的疫苗诱导人单克隆抗体对SARS-CoV-2变体的保护作用。
