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

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.