Diverse immunoglobulin gene usage and convergent epitope targeting in neutralizing antibody responses to SARS-CoV-2

Zhou, Xiaojuan; Ma, Fengge; Xie, Jun; Yuan, Meng; Li, Yunqiao; Shaabani, Namir; Zhao, Fangzhu; Huang, Deli; Wu, Nicholas C.; Lee, Chang-Chun D.; Liu, Hejun; Li, Jiali; Chen, Zhonghui; Hong, Yazhen; Liu, Wen-Hsien; Xiao, Nengming; Burton, Dennis R.; Tu, Haijian; Li, Hang; Chen, Xin; Teijaro, John R.; Wilson, Ian A.; Xiao, Changchun; Huang, Zhe

It is unclear whether individuals with enormous diversity in B cell receptor repertoires are consistently able to mount effective antibody responses against SARS-CoV-2. We analyzed antibody responses in a cohort of 55 convalescent patients and isolated 54 potent neutralizing monoclonal antibodies (mAbs). While most of the mAbs target the angiotensin-converting enzyme 2 (ACE2) binding surface on the receptor binding domain (RBD) of SARS-CoV-2 spike protein, mAb 47D1 binds only to one side of the receptor binding surface on the RBD. Neutralization by 47D1 is achieved independent of interfering RBD-ACE2 binding. A crystal structure of the mAb-RBD complex shows that the IF motif at the tip of 47D1 CDR H2 interacts with a hydrophobic pocket in the RBD. Diverse immunoglobulin gene usage and convergent epitope targeting characterize neutralizing antibody responses to SARS-CoV-2, suggesting that vaccines that effectively present the receptor binding site on the RBD will likely elicit neutralizing antibody responses in a large fraction of the population.