Influenza A virus hemagglutinin head trimer interface epitope (HA head trimer interface)

The Influenza A virus hemagglutinin (HA) head trimer interface epitope is a highly conserved site located within the globular head domain of the HA protein, which is typically occluded in the native, pre-fusion trimeric conformation. Unlike the immunodominant head regions that undergo rapid antigenic drift, the residues at the trimer interface are relatively stable across diverse influenza strains, making them an attractive target for broadly neutralizing antibodies (bnAbs). These antibodies, such as FluA-20, function by recognizing the epitope when the HA head domains transiently 'breathe' or dissociate, subsequently preventing the structural rearrangements necessary for viral-host membrane fusion. By targeting this hidden site, therapeutics can achieve cross-reactivity against multiple subtypes of Influenza A, including both Group 1 and Group 2 viruses. This epitope represents a significant shift in vaccine and monoclonal antibody design, moving away from the highly variable receptor-binding site toward more conserved, functionally critical structural regions of the virus.

Other names

HA head interfaceHemagglutinin trimer interface epitopeOccluded HA head epitopeInfluenza A HA head interfaceHA1-HA1 interface

Antibodies targeting this epitope bind to the normally occluded interface between the globular head domains of the hemagglutinin trimer, leading to trimer dissociation or preventing the conformational changes required for viral membrane fusion and entry into the host cell.