Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies

作者：Yunlong Cao, Jing Wang, Fanchong Jian, Tianhe Xiao, Weiliang Song, Ayijiang Yisimayi, Weijin Huang, Qianqian Li, Peng Wang, Ran An, Jing Wang, Yao Wang, Yao Wang, Niu Xiao, Sijie Yang, Hui Liang, Haiyan Sun, Tao Li, Yuanling Yu, Qianqian Cui, Shuo Liu, Xiaodong Yang, Shuo Du, Zhiying Zhang, Fei Shao, Fei Shao, Ronghua Jin, Xiangxi Wang, Junyu Xiao, Youchun Wang, Youchun Wang, Xiaoliang Sunney Xie · 发表于：Nature · 年份：2021 · DOI：10.1038/s41586-021-04385-3 · 被引用次数：2139 · 研究领域：SARS-CoV-2 and COVID-19 Research、Bacillus and Francisella bacterial research、COVID-19 Clinical Research Studies

Abstract The SARS-CoV-2 B.1.1.529 (Omicron) variant contains 15 mutations of the receptor-binding domain (RBD). How Omicron evades RBD-targeted neutralizing antibodies requires immediate investigation. Here we use high-throughput yeast display screening 1,2 to determine the profiles of RBD escaping mutations for 247 human anti-RBD neutralizing antibodies and show that the neutralizing antibodies can be classified by unsupervised clustering into six epitope groups (A–F)—a grouping that is highly concordant with knowledge-based structural classifications 3–5 . Various single mutations of Omicron can impair neutralizing antibodies of different epitope groups. Specifically, neutralizing antibodies in groups A–D, the epitopes of which overlap with the ACE2-binding motif, are largely escaped by K417N, G446S, E484A and Q493R. Antibodies in group E (for example, S309) 6 and group F (for example, CR3022) 7 , which often exhibit broad sarbecovirus neutralizing activity, are less affected by Omicron, but a subset of neutralizing antibodies are still escaped by G339D, N440K and S371L. Furthermore, Omicron pseudovirus neutralization showed that neutralizing antibodies that sustained single mutations could also be escaped, owing to multiple synergetic mutations on their epitopes. In total, over 85% of the tested neutralizing antibodies were escaped by Omicron. With regard to neutralizing-antibody-based drugs, the neutralization potency of LY-CoV016, LY-CoV555, REGN10933, REGN10987, AZD1061...