A Site of Vulnerability on the Influenza Virus Hemagglutinin Head Domain Trimer Interface

Sandhya Bangaru, Shanshan Lang, Michael Schotsaert, Hillary A. Vanderven, Xueyong Zhu, Nurgun Kose, Robin Bombardi, Jessica A. Finn, Stephen J. Kent, Pavlo Gilchuk, Iuliia Gilchuk, Hannah L. Turner, Adolfo García-Sastre, Sheng Li, Andrew B. Ward, Ian A. Wilson, James E. Crowe

Research output: Contribution to journalArticlepeer-review

128 Scopus citations


Here, we describe the discovery of a naturally occurring human antibody (Ab), FluA-20, that recognizes a new site of vulnerability on the hemagglutinin (HA) head domain and reacts with most influenza A viruses. Structural characterization of FluA-20 with H1 and H3 head domains revealed a novel epitope in the HA trimer interface, suggesting previously unrecognized dynamic features of the trimeric HA protein. The critical HA residues recognized by FluA-20 remain conserved across most subtypes of influenza A viruses, which explains the Ab's extraordinary breadth. The Ab rapidly disrupted the integrity of HA protein trimers, inhibited cell-to-cell spread of virus in culture, and protected mice against challenge with viruses of H1N1, H3N2, H5N1, or H7N9 subtypes when used as prophylaxis or therapy. The FluA-20 Ab has uncovered an exceedingly conserved protective determinant in the influenza HA head domain trimer interface that is an unexpected new target for anti-influenza therapeutics and vaccines. Antibodies targeting a novel site in the head domain of hemagglutinin afford broad protection against influenza.

Original languageEnglish
Pages (from-to)1136-1152.e18
Issue number5
StatePublished - 16 May 2019


  • B-lymphocytes
  • antibodies
  • antibodies
  • antibody-dependent cell cytotoxicity
  • antigen-antibody reactions
  • hemagglutinin glycoproteins
  • influenza A virus
  • influenza virus
  • monoclonal
  • viral


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