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Exposure of an occluded hemagglutinin epitope drives selection of a class of cross-protective influenza antibodies

Author

Listed:
  • Yu Adachi

    (National Institute of Infectious Diseases)

  • Keisuke Tonouchi

    (National Institute of Infectious Diseases
    Waseda University)

  • Arnone Nithichanon

    (National Institute of Infectious Diseases
    Khon Kaen University)

  • Masayuki Kuraoka

    (Duke University)

  • Akiko Watanabe

    (Duke University)

  • Ryo Shinnakasu

    (Osaka University)

  • Hideki Asanuma

    (National Institute of Infectious Diseases
    National Institute of Infectious Diseases)

  • Akira Ainai

    (National Institute of Infectious Diseases)

  • Yusuke Ohmi

    (Chubu University College of Life and Health Sciences)

  • Takuya Yamamoto

    (National Institutes of Biomedical Innovation, Health and Nutrition)

  • Ken J. Ishii

    (National Institutes of Biomedical Innovation, Health and Nutrition
    The Institute of Medical Science, The University of Tokyo)

  • Hideki Hasegawa

    (National Institute of Infectious Diseases
    National Institute of Infectious Diseases)

  • Haruko Takeyama

    (Waseda University)

  • Ganjana Lertmemongkolchai

    (Khon Kaen University)

  • Tomohiro Kurosaki

    (Osaka University
    RIKEN Center for Integrative Medical Sciences)

  • Manabu Ato

    (National Institute of Infectious Diseases)

  • Garnett Kelsoe

    (Duke University
    Human Vaccine Institute, Duke University)

  • Yoshimasa Takahashi

    (National Institute of Infectious Diseases)

Abstract

Germinal center (GC) B cells at viral replication sites acquire specificity to poorly immunogenic but conserved influenza hemagglutinin (HA) epitopes. Here, high-throughput epitope mapping of local GC B cells is used to identify conserved HA epitope selecting cross-reactive antibodies that mediate heterosubtypic protection. A distinct feature of this epitope is an occlusion in the naive trimeric HA structure that is exposed in the post-fusion HA structure to occur under low pH conditions during viral replication. Importantly, systemic immunization by the post-fusion HA antigen results in GC B cells targeting the occluded epitope, and induces a class of protective antibodies that have cross-group specificity and afford protection independent of virus neutralization activity. Furthermore, this class of broadly protective antibodies develops at late time points and persists. Our results identify a class of cross-protective antibodies that are selected at the viral replication site, and provide insights into vaccine strategies using the occluded epitope.

Suggested Citation

  • Yu Adachi & Keisuke Tonouchi & Arnone Nithichanon & Masayuki Kuraoka & Akiko Watanabe & Ryo Shinnakasu & Hideki Asanuma & Akira Ainai & Yusuke Ohmi & Takuya Yamamoto & Ken J. Ishii & Hideki Hasegawa &, 2019. "Exposure of an occluded hemagglutinin epitope drives selection of a class of cross-protective influenza antibodies," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11821-6
    DOI: 10.1038/s41467-019-11821-6
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