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

Yunlong Cao (), Jing Wang, Fanchong Jian, Tianhe Xiao, Weiliang Song, Ayijiang Yisimayi, Weijin Huang, Qianqian Li, Peng Wang, Ran An, Jing Wang, Yao Wang, Xiao Niu, Sijie Yang, Hui Liang, Haiyan Sun, Tao Li, Yuanling Yu, Qianqian Cui, Shuo Liu, Xiaodong Yang, Shuo Du, Zhiying Zhang, Xiaohua Hao, Fei Shao, Ronghua Jin, Xiangxi Wang (), Junyu Xiao (), Youchun Wang () and Xiaoliang Sunney Xie ()
Additional contact information
Yunlong Cao: Peking University
Jing Wang: Peking University
Fanchong Jian: Peking University
Tianhe Xiao: Peking University
Weiliang Song: Peking University
Ayijiang Yisimayi: Peking University
Weijin Huang: National Institutes for Food and Drug Control (NIFDC)
Qianqian Li: National Institutes for Food and Drug Control (NIFDC)
Peng Wang: Peking University
Ran An: Peking University
Jing Wang: Peking University
Yao Wang: Peking University
Xiao Niu: Peking University
Sijie Yang: Peking University
Hui Liang: Peking University
Haiyan Sun: Peking University
Tao Li: National Institutes for Food and Drug Control (NIFDC)
Yuanling Yu: National Institutes for Food and Drug Control (NIFDC)
Qianqian Cui: National Institutes for Food and Drug Control (NIFDC)
Shuo Liu: National Institutes for Food and Drug Control (NIFDC)
Xiaodong Yang: Capital Medical University
Shuo Du: Peking University
Zhiying Zhang: Peking University
Xiaohua Hao: Capital Medical University
Fei Shao: Peking University
Ronghua Jin: Capital Medical University
Xiangxi Wang: Chinese Academy of Sciences
Junyu Xiao: Peking University
Youchun Wang: National Institutes for Food and Drug Control (NIFDC)
Xiaoliang Sunney Xie: Peking University

Nature, 2022, vol. 602, issue 7898, 657-663

Abstract: 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 screening1,2 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 classifications3–5. 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, AZD8895 and BRII-196 was greatly undermined by Omicron, whereas VIR-7831 and DXP-604 still functioned at a reduced efficacy. Together, our data suggest that infection with Omicron would result in considerable humoral immune evasion, and that neutralizing antibodies targeting the sarbecovirus conserved region will remain most effective. Our results inform the development of antibody-based drugs and vaccines against Omicron and future variants.

Date: 2022
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DOI: 10.1038/s41586-021-04385-3

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