Human IgG neutralizing monoclonal antibodies block SARS-CoV-2 infection

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

Summary COVID-19 has become a worldwide threat to humans, and neutralizing antibodies have therapeutic potential. We have purified more than one thousand memory B cells specific to SARS-CoV-2 S1 or 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, 8 of which show an IC50 within 10 nM, and the best one, 414-1, with IC50 of 1.75 nM. Through epitope mapping, we find 3 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.