Human antibody recognition of H7N9 influenza virus HA following natural infection

Abstract

Avian H7N9 influenza viruses cause sporadic outbreaks of human infections and threaten to cause a major pandemic. The breadth of B cell responses to natural infection and the dominant antigenic sites recognized during first exposure to H7 HA following infection are incompletely understood. Here, we studied the B cell response to H7 HA of two individuals who had recovered from natural H7N9 virus infection. We used competition-binding, hydrogen-deuterium mass spectrometry, and single-particle negative stain electron microscopy to identify the patterns of molecular recognition of the antibody responses to H7 hemagglutinin. We found that circulating H7-reactive B cells recognized a diverse antigenic landscape on the HA molecule, including HA head domain epitopes in antigenic Sites A, B, and the trimer interface-II region and epitopes in the stem region. Most H7 antibodies exhibited little heterosubtypic breadth, but many recognized a wide diversity of unrelated H7 strains. We tested the antibodies for functional activity and identified clones with diverse patterns of inhibition, including neutralizing, hemagglutination or egress inhibiting, or HA trimer-disrupting activities. Thus, the human B cell response to primary H7 natural infection is diverse, highly functional, and broad for recognition of diverse H7 strains.

Epitopes in the HA and NA of H5 and H7 avian influenza viruses that are important for antigenic drift

“…Computational analysis of Eurasian H7s antigenic epitopes revealed higher substitution rates in epitopes A and B, whereas substitutions in North American H7s were higher in epitopes B and C (Liu et al 2015 ). Following natural infection of humans with H7N9 AIV, isolated mAbs predominantly bound antigenic site A or trimer interface site II, although mAbs that had haemagglutination inhibition (HI) activity predominately bound to antigenic sites A and B (Gilchuk et al 2021 ). Characterization of a panel of murine mAbs raised against H7N9 AIV demonstrated that all mAbs with neutralizing activity primarily targeted antigenic site A and to a lesser extent, to antigenic sites A and D (Ito et al 2019 ).…”