Diverse immunoglobulin gene usage and convergent epitope targeting in neutralizing antibody responses to SARS-CoV-2
Xiaojuan Zhou, Fengge Ma, Jun Xie, Meng Yuan, Yunqiao Li, Namir Shaabani, Fangzhu Zhao, Deli Huang, Nicholas C. Wu, Chang‐Chun D. Lee, Hejun Liu, Jiali Li, Zhonghui Chen, Yazhen Hong, Wen‐Hsien Liu, Nengming Xiao, Dennis R. Burton, Haijian Tu, Hang Li, Xin Chen, John R. Teijaro, Ian A. Wilson, Changchun Xiao, Zhe Huang
Abstract
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.