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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • August 28, 2019

Published In

Volume / Issue

  • 10 / 1

Start / End Page

  • 3883 -

PubMed ID

  • 31462639

Pubmed Central ID

  • 31462639

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-019-11821-6

Language

  • eng

Conference Location

  • England