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Human antibody 3E1 targets the HA stem region of H1N1 and H5N6 influenza A viruses

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  • Wenshuai Wang

    (National Center for Protein Science Shanghai, State Key Laboratory of Molecular Biology, Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences and University of Chinese Academy of Sciences, Chinese Academy of Sciences)

  • Xiaoyu Sun

    (CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, University of Chinese Academy of Sciences)

  • Yanbing Li

    (State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences)

  • Jinpeng Su

    (State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences)

  • Zhiyang Ling

    (State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences)

  • Tianlong Zhang

    (National Center for Protein Science Shanghai, State Key Laboratory of Molecular Biology, Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences and University of Chinese Academy of Sciences, Chinese Academy of Sciences)

  • Fang Wang

    (National Center for Protein Science Shanghai, State Key Laboratory of Molecular Biology, Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences and University of Chinese Academy of Sciences, Chinese Academy of Sciences)

  • Hong Zhang

    (CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, University of Chinese Academy of Sciences)

  • Hualan Chen

    (State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences)

  • Jianping Ding

    (National Center for Protein Science Shanghai, State Key Laboratory of Molecular Biology, Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences and University of Chinese Academy of Sciences, Chinese Academy of Sciences
    Shanghai Science Research Center, Chinese Academy of Sciences)

  • Bing Sun

    (CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, University of Chinese Academy of Sciences
    State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences)

Abstract

As influenza A viruses remain a major threat to human health worldwide, the discovery of broadly neutralizing monoclonal antibodies that recognize conserved epitopes would facilitate the development of antibody-based therapeutic strategies. Here we report that a VH4-4-encoded human mAb named 3E1 could neutralize H1 and H5 subtype viruses in vitro and protect mice against the H1N1 and H5N6 viruses by inhibiting the low pH-induced conformational rearrangement of haemagglutinin (HA), hence blocking membrane fusion. The crystal structures of 3E1 Fab in complex with HA of two H1N1 strains reveal that 3E1, with both heavy and light chains, binds to a conserved epitope of the HA stem region, comprising parts of the fusion peptide, the F subdomain and the outermost β-strand preceding helix A. Altogether, these data suggest the potential of 3E1 as a therapeutic drug against H1 and H5 subtype viruses.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13577
    DOI: 10.1038/ncomms13577
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    Cited by:

    1. 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.
    2. Yulu Chen & Fei Wang & Liwei Yin & Haihai Jiang & Xishan Lu & Yuhai Bi & Wei Zhang & Yi Shi & Roberto Burioni & Zhou Tong & Hao Song & Jianxun Qi & George F. Gao, 2022. "Structural basis for a human broadly neutralizing influenza A hemagglutinin stem-specific antibody including H17/18 subtypes," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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