| Specificity: FluA-20 activity is directed against a novel epitope at the trimer interface of the hemagglutinin (HA) head domain of most influenza A viruses. Furthermore this antibody binds to HA trimers from a wide array of strains (H1, H2, H3, H4, H5, H6, 2/3 of H7 strains tested, H8, H9, H10, H11, H12, H14, H15) but not H16. Structural studies of FluA-20 with the HA head domain revealed a novel epitope that is mostly buried in the peripheral interface of the native HA trimer on the non-receptor-binding site side of the 220-loop, adjacent to the 90-loop1. Many FluA-20 to HA contacts are centered on Arg229, and alanine mutation of Arg229 abolishes binding. Other mutations, at residues Arg220, Val223 or Pro96, also substantially decrease binding. These results are similar in H1, H3, and H5 strains. The key residues recognized by FluA-20, Pro96, Arg220, Pro221, Val223, and Arg229, are highly conserved across diverse subtypes. Antigen Distribution: HA is on the viral surface. Background: Hemagglutinin (HA) is a glycoprotein on the Influenza A (IAV) viral surface1. HA consists of two domains: an antigenically variable head and a more conserved stem. There are 18 HA subtypes. Neutralizing antibodies targeting the head domain are typically restricted to within subtype, while antibodies targeting the stem offer broader protection. In contrast, FluA-20 is a human antibody that recognizes the HA head domain of nearly all subtypes of IAV with high affinity1. |
