Identification of Antibodies Targeting the H3N2 Hemagglutinin Receptor Binding Site following Vaccination of Humans

Seth J. Zost, Juhye Lee, Megan E. Gumina, Kaela Parkhouse, Carole Henry, Nicholas C. Wu, Chang Chun D. Lee, Ian A. Wilson, Patrick C. Wilson, Jesse D. Bloom, Scott E. Hensley

Research output: Contribution to journalArticlepeer-review

Abstract

Antibodies targeting the receptor binding site (RBS) of the influenza virus hemagglutinin (HA) protein are usually not broadly reactive because their footprints are typically large and extend to nearby variable HA residues. Here, we identify several human H3N2 HA RBS-targeting monoclonal antibodies (mAbs) that are sensitive to substitutions in conventional antigenic sites and are therefore not broadly reactive. However, we also identify an H3N2 HA RBS-targeting mAb that is exceptionally broadly reactive despite being sensitive to substitutions in residues outside of the RBS. We show that similar antibodies are present at measurable levels in the sera of some individuals but that they are inefficiently elicited by conventional vaccines. Our data indicate that HA RBS-targeting antibodies can be effective against variable viral strains even when they are somewhat sensitive to substitutions in HA residues adjacent to the RBS.

Original languageEnglish (US)
Pages (from-to)4460-4470.e8
JournalCell Reports
Volume29
Issue number13
DOIs
StatePublished - Dec 24 2019
Externally publishedYes

Keywords

  • antibodies
  • hemagglutinin
  • influenza
  • vaccine

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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