Antibodies utilizing VL6-57 light chains target a convergent cryptic epitope on SARS-CoV-2 spike protein and potentially drive the genesis of Omicron variants
Continued evolution of SARS-CoV-2 generates variants to challenge antibody immunity established by infection and vaccination. A connection between population immunity and genesis of virus variants has long been suggested but its molecular basis remains poorly understood. Here, we identify a class of SARS-CoV-2 neutralizing public antibodies defined by their shared usage of VL6-57 light chains. Although heavy chains of diverse genotypes are utilized, convergent HCDR3 rearrangements have been observed among these public antibodies to cooperate with germline VL6-57 LCDRs to target a convergent epitope defined by RBD residues S371-S373-S375. Antibody repertoire analysis identifies that this class of VL6-57 antibodies is present in SARS-CoV-2-naive individuals and is clonally expanded in most COVID-19 patients. We confirm that Omicron-specific substitutions at S371, S373 and S375 mediate escape of antibodies of the VL6-57 class. These findings support that this class of public antibodies constitutes a potential immune pressure promoting the introduction of S371L/F-S373P-S375F in Omicron variants. The results provide further molecular evidence to support that antigenic evolution of SARS-CoV-2 is driven by antibody mediated population immunity.
Authors
- Ruitian Hou
- Xiaoli Xiong (ORCID: https://orcid.org/0000-0002-4632-9122)
- Xianying Chen (ORCID: https://orcid.org/0000-0002-1214-3143)
- Ping He (ORCID: https://orcid.org/0000-0002-4087-2247)
- Jun He (ORCID: https://orcid.org/0000-0003-0270-9729)
- Jincun Zhao (ORCID: https://orcid.org/0000-0003-2515-5589)
- Yichen Yao (ORCID: https://orcid.org/0009-0000-1378-7170)
- Xijie Gao (ORCID: https://orcid.org/0000-0002-0602-4690)
- Huan Liang (ORCID: https://orcid.org/0000-0002-8918-4904)
- Banghui Liu (ORCID: https://orcid.org/0000-0001-6487-803X)
- Qiuluan Chen
- Qihong Yan (ORCID: https://orcid.org/0000-0003-1645-8764)
- Ling Chen (ORCID: https://orcid.org/0000-0003-1485-1626)
- Jingjing Wang (ORCID: https://orcid.org/0000-0001-5315-5469)
- Yanjun Zhang (ORCID: https://orcid.org/0000-0002-9702-1128)
- Xiaohan Huang (ORCID: https://orcid.org/0000-0001-7370-9289)
- Zimu Li (ORCID: https://orcid.org/0000-0002-2305-7275)
- Yong Ma
- Xuefeng Niu
- Huiran Zheng
- Yudi Zhang (ORCID: https://orcid.org/0000-0003-2597-3389)
Institutions
- Guangzhou Institutes of Biomedicine and Health (CN)
- ShanghaiTech University (CN)
- First Affiliated Hospital of Guangzhou Medical University (CN)
- Guangzhou Regenerative Medicine and Health Guangdong Laboratory (CN)
- Guangzhou Chemistry (China) (CN)
- State Key Laboratory of Respiratory Disease (CN)
- Guangzhou Eighth People's Hospital (CN)
- University of Chinese Academy of Sciences (CN)
- Guangzhou Medical University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-08-31
- DOI
- https://doi.org/10.1038/s41467-024-51770-3
- Citations
- 9
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 3.50