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A potent broad-spectrum protective human monoclonal antibody crosslinking two haemagglutinin monomers of influenza A virus

Author

Listed:
  • Ying Wu

    (CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
    Center for Influenza Research and Early-warning, Chinese Academy of Sciences)

  • MyungSam Cho

    (Biotechnology Research Institute, Celltrion, Inc.)

  • David Shore

    (Centers for Disease Control and Prevention)

  • Manki Song

    (International Vaccine Institute)

  • JungAh Choi

    (International Vaccine Institute)

  • Tao Jiang

    (State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology)

  • Yong-Qiang Deng

    (State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology)

  • Melissa Bourgeois

    (Centers for Disease Control and Prevention)

  • Lynn Almli

    (Centers for Disease Control and Prevention)

  • Hua Yang

    (Centers for Disease Control and Prevention)

  • Li-Mei Chen

    (Centers for Disease Control and Prevention)

  • Yi Shi

    (CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
    Center for Influenza Research and Early-warning, Chinese Academy of Sciences
    Research Network of Immunity and Health, Beijing Institutes of Life Science, Chinese Academy of Sciences)

  • Jianxu Qi

    (CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
    Center for Influenza Research and Early-warning, Chinese Academy of Sciences)

  • An Li

    (CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
    College of Veterinary Medicine, Guangxi University)

  • Kye Sook Yi

    (Biotechnology Research Institute, Celltrion, Inc.)

  • MinSeok Chang

    (Biotechnology Research Institute, Celltrion, Inc.)

  • Jin Soo Bae

    (Biotechnology Research Institute, Celltrion, Inc.)

  • HyunJoo Lee

    (Biotechnology Research Institute, Celltrion, Inc.)

  • JiYoung Shin

    (Biotechnology Research Institute, Celltrion, Inc.)

  • James Stevens

    (Centers for Disease Control and Prevention)

  • SeoungSuh Hong

    (Biotechnology Research Institute, Celltrion, Inc.)

  • Cheng-Feng Qin

    (State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology)

  • George F. Gao

    (CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
    Center for Influenza Research and Early-warning, Chinese Academy of Sciences
    Research Network of Immunity and Health, Beijing Institutes of Life Science, Chinese Academy of Sciences
    Office of Director-General, Chinese Center for Disease Control and Prevention (China CDC))

  • Shin Jae Chang

    (Biotechnology Research Institute, Celltrion, Inc.)

  • Ruben O. Donis

    (Centers for Disease Control and Prevention)

Abstract

Effective annual influenza vaccination requires frequent changes in vaccine composition due to both antigenic shift for different subtype hemagglutinins (HAs) and antigenic drift in a particular HA. Here we present a broadly neutralizing human monoclonal antibody with an unusual binding modality. The antibody, designated CT149, was isolated from convalescent patients infected with pandemic H1N1 in 2009. CT149 is found to neutralize all tested group 2 and some group 1 influenza A viruses by inhibiting low pH-induced, HA-mediated membrane fusion. It promotes killing of infected cells by Fc-mediated antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. X-ray crystallographic data reveal that CT149 binds primarily to the fusion domain in HA2, and the light chain is also largely involved in binding. The epitope recognized by this antibody comprises amino-acid residues from two adjacent protomers of HA. This binding characteristic of CT149 will provide more information to support the design of more potent influenza vaccines.

Suggested Citation

  • Ying Wu & MyungSam Cho & David Shore & Manki Song & JungAh Choi & Tao Jiang & Yong-Qiang Deng & Melissa Bourgeois & Lynn Almli & Hua Yang & Li-Mei Chen & Yi Shi & Jianxu Qi & An Li & Kye Sook Yi & Min, 2015. "A potent broad-spectrum protective human monoclonal antibody crosslinking two haemagglutinin monomers of influenza A virus," Nature Communications, Nature, vol. 6(1), pages 1-11, November.
  • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8708
    DOI: 10.1038/ncomms8708
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