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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.

Duke Scholars

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
 

Citation

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MLA
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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

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