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

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, Haruko Takeyama, Ganjana Lertmemongkolchai, Tomohiro Kurosaki, Manabu Ato, Garnett Kelsoe, Yoshimasa Takahashi

研究成果: Article

6 引用 (Scopus)

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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.

元の言語English
記事番号3883
ジャーナルNature communications
10
発行部数1
DOI
出版物ステータスPublished - 2019 12 1

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Adachi, Y., Tonouchi, K., Nithichanon, A., Kuraoka, M., Watanabe, A., Shinnakasu, R., Asanuma, H., Ainai, A., Ohmi, Y., Yamamoto, T., Ishii, K. J., Hasegawa, H., Takeyama, H., Lertmemongkolchai, G., Kurosaki, T., Ato, M., Kelsoe, G., & Takahashi, Y. (2019). Exposure of an occluded hemagglutinin epitope drives selection of a class of cross-protective influenza antibodies. Nature communications, 10(1), [3883]. https://doi.org/10.1038/s41467-019-11821-6