Germline IGHV3-53-encoded RBD-targeting neutralizing antibodies are commonly present in the antibody repertoires of COVID-19 patients. Issue 1 (1st January 2021)

• Record Type: Journal Article
• Authors: Yan, Qihong; He, Ping; Huang, Xiaohan; Luo, Kun; Zhang, Yudi; Yi, Haisu; Wang, Qian; Li, Feng; Hou, Ruitian; Fan, Xiaodi; Li, Pingchao; Liu, Xinglong; Liang, Huan; Deng, Yijun; Chen, Zhaoming; Chen, Yunfei; Mo, Xiaoneng; Feng, Liqiang; Xiong, Xiaoli; Li, Song; Han, Jian; Qu, Linbing; Niu, Xuefeng; Chen, Ling
• Is Part Of: Emerging microbes & infections. Volume 10:Issue 1(2021)
• Page Start: 1097
• Page End: 1111
• Publication Date: 2021-01-01
• Subjects: SARS-CoV-2 -- IGHV3-53 -- shared clonotype -- receptor-binding domain -- antibody repertoire sequencing; Medical microbiology -- Periodicals; Communicable diseases -- Periodicals; Infection -- Periodicals; 616.9041
• DOI: 10.1080/22221751.2021.1925594
• Languages: English
• ISSNs: 2222-1751

Abstract

ABSTRACT: Monoclonal antibodies (mAbs) encoded by IGHV3-53 (VH3-53) targeting the spike receptor-binding domain (RBD) have been isolated from different COVID-19 patients. However, the existence and prevalence of shared VH3-53-encoded antibodies in the antibody repertoires is not clear. Using antibody repertoire sequencing, we found that the usage of VH3-53 increased after SARS-CoV-2 infection. A highly shared VH3-53-J6 clonotype was identified in 9 out of 13 COVID-19 patients. This clonotype was derived from convergent gene rearrangements with few somatic hypermutations and was evolutionary conserved. We synthesized 34 repertoire-deduced novel VH3-53-J6 heavy chains and paired with a common IGKV1-9 light chain to produce recombinant mAbs. Most of these recombinant mAbs (23/34) possess RBD binding and virus-neutralizing activities, and recognize ACE2 binding site via the same molecular interface. Our computational analysis, validated by laboratory experiments, revealed that VH3-53 antibodies targeting RBD are commonly present in COVID-19 patients' antibody repertoires, indicating many people have germline-like precursor sequences to rapidly generate SARS-CoV-2 neutralizing antibodies. Moreover, antigen-specific mAbs can be digitally obtained through antibody repertoire sequencing and computational analysis.