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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

Author

Listed:
  • Qihong Yan

    (the First Affiliated Hospital of Guangzhou Medical University)

  • Xijie Gao

    (The Fifth Affiliated Hospital of Guangzhou Medical University)

  • Banghui Liu

    (Chinese Academy of Sciences)

  • Ruitian Hou

    (Guangzhou Medical University)

  • Ping He

    (Guangzhou National Laboratory)

  • Yong Ma

    (Chinese Academy of Sciences)

  • Yudi Zhang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Yanjun Zhang

    (the First Affiliated Hospital of Guangzhou Medical University)

  • Zimu Li

    (Chinese Academy of Sciences)

  • Qiuluan Chen

    (Bioland Laboratory (Guangzhou Regenerative Medicine and Health - Guangdong Laboratory))

  • Jingjing Wang

    (Chinese Academy of Sciences)

  • Xiaohan Huang

    (the First Affiliated Hospital of Guangzhou Medical University)

  • Huan Liang

    (the First Affiliated Hospital of Guangzhou Medical University)

  • Huiran Zheng

    (the First Affiliated Hospital of Guangzhou Medical University)

  • Yichen Yao

    (ShanghaiTech University)

  • Xianying Chen

    (the First Affiliated Hospital of Guangzhou Medical University)

  • Xuefeng Niu

    (the First Affiliated Hospital of Guangzhou Medical University)

  • Jun He

    (Chinese Academy of Sciences)

  • Ling Chen

    (the First Affiliated Hospital of Guangzhou Medical University
    Chinese Academy of Sciences
    Guangzhou National Laboratory)

  • Jincun Zhao

    (the First Affiliated Hospital of Guangzhou Medical University
    Guangzhou National Laboratory
    ShanghaiTech University)

  • Xiaoli Xiong

    (Chinese Academy of Sciences)

Abstract

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.

Suggested Citation

  • Qihong Yan & Xijie Gao & Banghui Liu & Ruitian Hou & Ping He & Yong Ma & Yudi Zhang & Yanjun Zhang & Zimu Li & Qiuluan Chen & Jingjing Wang & Xiaohan Huang & Huan Liang & Huiran Zheng & Yichen Yao & X, 2024. "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," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51770-3
    DOI: 10.1038/s41467-024-51770-3
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