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Unique binding pattern for a lineage of human antibodies with broad reactivity against influenza A virus

Author

Listed:
  • Xiaoyu Sun

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

  • Caixuan Liu

    (Chinese Academy of Sciences)

  • Xiao Lu

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

  • Zhiyang Ling

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

  • Chunyan Yi

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

  • Zhen Zhang

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

  • Zi Li

    (Chinese Center for Disease Control and Prevention)

  • Mingliang Jin

    (Chinese Academy of Sciences)

  • Wenshuai Wang

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

  • Shubing Tang

    (Fudan University)

  • Fangfang Wang

    (The National Facility for Protein Science in Shanghai (NFPS))

  • Fang Wang

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

  • Sonam Wangmo

    (Chinese Academy of Sciences; University of Chinese Academy of Sciences
    ShanghaiTech University)

  • Shuangfeng Chen

    (Chinese Academy of Sciences; University of Chinese Academy of Sciences
    ShanghaiTech University)

  • Li Li

    (ShanghaiTech University)

  • Liyan Ma

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

  • Yaguang Zhang

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

  • Zhuo Yang

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

  • Xiaoping Dong

    (Chinese Center for Disease Control and Prevention)

  • Zhikang Qian

    (University of the Chinese Academy of Sciences)

  • Jianping Ding

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

  • Dayan Wang

    (Chinese Center for Disease Control and Prevention)

  • Yao Cong

    (Chinese Academy of Sciences)

  • Bing Sun

    (Chinese Academy of Sciences; University of Chinese Academy of Sciences
    ShanghaiTech University)

Abstract

Most structurally characterized broadly neutralizing antibodies (bnAbs) against influenza A viruses (IAVs) target the conserved conformational epitopes of hemagglutinin (HA). Here, we report a lineage of naturally occurring human antibodies sharing the same germline gene, VH3-48/VK1-12. These antibodies broadly neutralize the major circulating strains of IAV in vitro and in vivo mainly by binding a contiguous epitope of H3N2 HA, but a conformational epitope of H1N1 HA, respectively. Our structural and functional studies of antibody 28-12 revealed that the continuous amino acids in helix A, particularly N49HA2 of H3 HA, are critical to determine the binding feature with 28-12. In contrast, the conformational epitope feature is dependent on the discontinuous segments involving helix A, the fusion peptide, and several HA1 residues within H1N1 HA. We report that this antibody was initially selected by H3 (group 2) viruses and evolved via somatic hypermutation to enhance the reactivity to H3 and acquire cross-neutralization to H1 (group 1) virus. These findings enrich our understanding of different antigenic determinants of heterosubtypic influenza viruses for the recognition of bnAbs and provide a reference for the design of influenza vaccines and more effective antiviral drugs.

Suggested Citation

  • Xiaoyu Sun & Caixuan Liu & Xiao Lu & Zhiyang Ling & Chunyan Yi & Zhen Zhang & Zi Li & Mingliang Jin & Wenshuai Wang & Shubing Tang & Fangfang Wang & Fang Wang & Sonam Wangmo & Shuangfeng Chen & Li Li , 2022. "Unique binding pattern for a lineage of human antibodies with broad reactivity against influenza A virus," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29950-w
    DOI: 10.1038/s41467-022-29950-w
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    References listed on IDEAS

    as
    1. Wenshuai Wang & Xiaoyu Sun & Yanbing Li & Jinpeng Su & Zhiyang Ling & Tianlong Zhang & Fang Wang & Hong Zhang & Hualan Chen & Jianping Ding & Bing Sun, 2016. "Human antibody 3E1 targets the HA stem region of H1N1 and H5N6 influenza A viruses," Nature Communications, Nature, vol. 7(1), pages 1-12, December.
    2. Ying Fu & Zhen Zhang & Jared Sheehan & Yuval Avnir & Callie Ridenour & Thomas Sachnik & Jiusong Sun & M. Jaber Hossain & Li-Mei Chen & Quan Zhu & Ruben O. Donis & Wayne A. Marasco, 2016. "A broadly neutralizing anti-influenza antibody reveals ongoing capacity of haemagglutinin-specific memory B cells to evolve," Nature Communications, Nature, vol. 7(1), pages 1-13, November.
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