ABSTRACT Novel animal influenza viruses emerge, initiate pandemics and become endemic seasonal variants that have evolved to escape from prevalent herd immunity. These processes often outpace vaccine-elicited protection. Focusing immune responses on conserved epitopes may impart durable immunity. We describe a focused, protective antibody response, abundant in memory and serum repertoires, to a conserved region at the influenza hemagglutinin head interface. Structures of eleven examples, eight reported here, from seven human donors demonstrate the convergence of responses on a single epitope. The eleven are genetically diverse, with one class having a common, IGκV1-39, light chain. All of the antibodies bind HAs from multiple serotypes. The lack of apparent genetic restriction and potential for elicitation by more than one serotype may explain their abundance. We define the head interface as a major target of broadly protective antibodies with the potential to influence the outcomes of influenza infection.

A prevalent focused human antibody response to the influenza hemagglutinin head interface