[PDF][PDF] A site of vulnerability on the influenza virus hemagglutinin head domain trimer interface

S Bangaru, S Lang, M Schotsaert, HA Vanderven… - Cell, 2019 - cell.com
S Bangaru, S Lang, M Schotsaert, HA Vanderven, X Zhu, N Kose, R Bombardi, JA Finn
Cell, 2019cell.com
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 …
Summary
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.
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