A Prevalent Focused Human Antibody Response to the Influenza Virus Hemagglutinin Head Interface
Kevin R. McCarthy, Jiwon Lee, Akiko Watanabe, Masayuki Kuraoka, Lindsey R. Robinson‐McCarthy, George Georgiou, Garnett Kelsoe, Stephen C. Harrison
Abstract
The rapid appearance of mutations in circulating human influenza viruses and selection for escape from herd immunity require prediction of likely variants for an annual updating of influenza vaccines. The identification of human antibodies that recognize conserved surfaces on the influenza virus hemagglutinin (HA) has prompted efforts to design immunogens that might selectively elicit such antibodies. The recent discovery of a widely prevalent antibody response to the conserved interface between two HA "heads" (the globular, receptor-binding domains at the apex of the spike-like trimer) has added a new target for these efforts. We report structures of eight such antibodies, bound with HA heads, and compare them with each other and with three others previously described. Although genetically diverse, they all converge on a common binding site. The analysis here can guide immunogen design for preclinical trials.