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

Publication ,  Journal Article
Adachi, Y; Tonouchi, K; Nithichanon, A; Kuraoka, M; Watanabe, A; Shinnakasu, R; Asanuma, H; Ainai, A; Ohmi, Y; Yamamoto, T; Ishii, KJ; Ato, M ...
Published in: Nat Commun
August 28, 2019

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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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

August 28, 2019

Volume

10

Issue

1

Start / End Page

3883

Location

England

Related Subject Headings

  • Virus Replication
  • Mice, SCID
  • Mice, Knockout
  • Mice, Inbred NOD
  • Mice, Inbred BALB C
  • Influenza A virus
  • Immunization
  • Humans
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Germinal Center
 

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Adachi, Y., Tonouchi, K., Nithichanon, A., Kuraoka, M., Watanabe, A., Shinnakasu, R., … Takahashi, Y. (2019). Exposure of an occluded hemagglutinin epitope drives selection of a class of cross-protective influenza antibodies. Nat Commun, 10(1), 3883. https://doi.org/10.1038/s41467-019-11821-6
Adachi, Yu, Keisuke Tonouchi, Arnone Nithichanon, Masayuki Kuraoka, Akiko Watanabe, Ryo Shinnakasu, Hideki Asanuma, et al. “Exposure of an occluded hemagglutinin epitope drives selection of a class of cross-protective influenza antibodies.Nat Commun 10, no. 1 (August 28, 2019): 3883. https://doi.org/10.1038/s41467-019-11821-6.
Adachi Y, Tonouchi K, Nithichanon A, Kuraoka M, Watanabe A, Shinnakasu R, et al. Exposure of an occluded hemagglutinin epitope drives selection of a class of cross-protective influenza antibodies. Nat Commun. 2019 Aug 28;10(1):3883.
Adachi, Yu, et al. “Exposure of an occluded hemagglutinin epitope drives selection of a class of cross-protective influenza antibodies.Nat Commun, vol. 10, no. 1, Aug. 2019, p. 3883. Pubmed, doi:10.1038/s41467-019-11821-6.
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. Exposure of an occluded hemagglutinin epitope drives selection of a class of cross-protective influenza antibodies. Nat Commun. 2019 Aug 28;10(1):3883.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

August 28, 2019

Volume

10

Issue

1

Start / End Page

3883

Location

England

Related Subject Headings

  • Virus Replication
  • Mice, SCID
  • Mice, Knockout
  • Mice, Inbred NOD
  • Mice, Inbred BALB C
  • Influenza A virus
  • Immunization
  • Humans
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Germinal Center