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

Yu AdachiKeisuke TonouchiArnone NithichanonMasayuki KuraokaAkiko WatanabeRyo ShinnakasuHideki AsanumaAkira AinaiYusuke OhmiTakuya YamamotoKen J IshiiHideki HasegawaHaruko TakeyamaGanjana LertmemongkolchaiTomohiro KurosakiManabu AtoGarnett KelsoeYoshimasa Takahashi
Published in: Nature communications (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.
Keyphrases
  • monoclonal antibody
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  • high throughput
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  • machine learning
  • high resolution
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