Human-IgG-Neutralizing Monoclonal Antibodies Block the SARS-CoV-2 Infection

• Published in: Cell reports (Cambridge) Vol. 32; no. 3; p. 107918
• Main Authors: Wan, Jinkai, Xing, Shenghui, Ding, Longfei, Wang, Yongheng, Gu, Chenjian, Wu, Yanling, Rong, Bowen, Li, Cheng, Wang, Siqing, Chen, Kun, He, Chenxi, Zhu, Dandan, Yuan, Songhua, Qiu, Chengli, Zhao, Chen, Nie, Lei, Gao, Zhangzhao, Jiao, Jingyu, Zhang, Xiaoyan, Wang, Xiangxi, Ying, Tianlei, Wang, Haibin, Xie, Youhua, Lu, Yanan, Xu, Jianqing, Lan, Fei
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.07.2020; The Author(s)
• Subjects: Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - therapeutic use; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; B-Lymphocytes - immunology; Betacoronavirus - immunology; coronavirus; Coronavirus Infections - therapy; COVID-19; cross-neutralizing antibody; epitope; Epitope Mapping; Epitopes - immunology; human antibodies; Humans; Immunologic Memory - immunology; infection; Neutralization Tests; neutralizing antibodies; Pandemics; Pneumonia, Viral - therapy; Protein Domains - immunology; RBD; Receptors, Virus - immunology; SARS-CoV-2; Spike Glycoprotein, Coronavirus - immunology; spike protein; COVID-19; SARS-CoV-2; infection; human antibodies; RBD; spike protein; neutralizing antibodies; coronavirus; epitope; cross-neutralizing antibody
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2020.107918

Coronavirus disease 2019 (COVID-19) has become a worldwide threat to humans, and neutralizing antibodies have therapeutic potential. We have purified more than 1,000 memory B cells specific to SARS-CoV-2 S1 or its RBD (receptor binding domain) and obtain 729 paired heavy- and light-chain fragments. Among these, 178 antibodies test positive for antigen binding, and the majority of the top 17 binders with EC50 below 1 nM are RBD binders. Furthermore, we identify 11 neutralizing antibodies, eight of which show IC50 within 10 nM, and the best one, 414-1, with IC50 of 1.75 nM. Through epitope mapping, we find three main epitopes in RBD recognized by these antibodies, and epitope-B antibody 553-15 could substantially enhance the neutralizing abilities of most of the other antibodies. We also find that 515-5 could cross neutralize the SARS-CoV pseudovirus. Altogether, our study provides 11 potent human neutralizing antibodies for COVID-19 as therapeutic candidates. [Display omitted] •11 neutralizing antibodies against SARS-CoV-2 target three main epitopes on RBD•Epitope-A antibody 414-1 shows neutralizing IC50 at 1.75 nM•Epitope-B antibody 553-15 can enhance the neutralizing abilities of other antibodies•One neutralizing antibody, 515-5, can cross neutralize SARS-CoV pseudovirus Wan et al. identify 11 potent neutralizing antibodies against COVID-19 from 11 convalescent patients. These human neutralizing antibodies target three separate epitopes on the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, and epitope-B antibody (553-15) can enhance the neutralizing abilities of most other antibodies.