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JCI insightAug 2021 DOI:
10.1172/jci.insight.152403

Human antibody recognition of H7N9 influenza virus hemagglutinin following natural infection

Gilchuk, Iuliia M; Bangaru, Sandhya; Kose, Nurgun; Bombardi, Robin G; Trivette, Andrew; Li, Sheng; Turner, Hannah L; Carnahan, Robert H; Ward, Andrew B; Crowe, James E
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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.
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