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

doi:10.1038/s41467-019-11821-6

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

School of Advanced Science and Engineering

Research output: Contribution to journal › Article

6 Citations (Scopus)

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.

Original language	English
Article number	3883
Journal	Nature communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-11821-6
Publication status	Published - 2019 Dec 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

Exposure of an occluded hemagglutinin epitope drives selection of a class of cross-protective influenza antibodies. / Adachi, Yu; Tonouchi, Keisuke; Nithichanon, Arnone; Kuraoka, Masayuki; Watanabe, Akiko; Shinnakasu, Ryo; Asanuma, Hideki; Ainai, Akira; Ohmi, Yusuke; Yamamoto, Takuya; Ishii, Ken J.; Hasegawa, Hideki; Takeyama, Haruko; Lertmemongkolchai, Ganjana; Kurosaki, Tomohiro; Ato, Manabu; Kelsoe, Garnett; Takahashi, Yoshimasa.

In: Nature communications, Vol. 10, No. 1, 3883, 01.12.2019.

Research output: Contribution to journal › Article

Adachi, Y, Tonouchi, K, Nithichanon, A, Kuraoka, M, Watanabe, A, Shinnakasu, R, Asanuma, H, Ainai, A, Ohmi, Y, Yamamoto, T, Ishii, KJ, 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, vol. 10, no. 1, 3883. https://doi.org/10.1038/s41467-019-11821-6

Adachi, Yu ; Tonouchi, Keisuke ; Nithichanon, Arnone ; Kuraoka, Masayuki ; Watanabe, Akiko ; Shinnakasu, Ryo ; Asanuma, Hideki ; Ainai, Akira ; Ohmi, Yusuke ; Yamamoto, Takuya ; Ishii, Ken J. ; Hasegawa, Hideki ; Takeyama, Haruko ; Lertmemongkolchai, Ganjana ; Kurosaki, Tomohiro ; Ato, Manabu ; Kelsoe, Garnett ; Takahashi, Yoshimasa. / Exposure of an occluded hemagglutinin epitope drives selection of a class of cross-protective influenza antibodies. In: Nature communications. 2019 ; Vol. 10, No. 1.

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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.",

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AU - Takeyama, Haruko

AU - Lertmemongkolchai, Ganjana

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