Antibodies to a Conserved Influenza Head Interface Epitope Protect by an IgG Subtype-Dependent Mechanism

Summary Vaccines to generate durable humoral immunityagainst antigenically evolving pathogens such as the influenza virus must elicit antibodies that recognize conserved epitopes. Analysis of single memory B cellsfrom immunized human donors has led us to characterize a previously unrecognized epitopeof influenza hemagglutinin(HA) that is immunogenicin humans and conserved among influenza subtypes. Structures show that an unrelated antibody from a participant in an experimental infection protocol recognized the epitopeas well. IgGs specific for this antigenic determinant do not block viral infection in vitro , but passive administration to mice affords robust IgG subtype-dependent protection against influenza infection. The epitope, occluded in the pre-fusion form of HA, is at the contact surface between HA head domains; reversible molecular "breathing" of the HA trimer can expose the interface to antibody and B cells. Antigens that present this broadly immunogenicHA epitopemay be good candidates for inclusion in " universal" flu vaccines.