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JCI Insight
. 2021 Aug 26;152403.
doi: 10.1172/jci.insight.152403. Online ahead of print.
Human antibody recognition of H7N9 influenza virus hemagglutinin following natural infection
Iuliia M Gilchuk 1 , Sandhya Bangaru 2 , Nurgun Kose 1 , Robin G Bombardi 1 , Andrew Trivette 1 , Sheng Li 3 , Hannah L Turner 4 , Robert H Carnahan 5 , Andrew B Ward 4 , James E Crowe Jr 1
Affiliations
- PMID: 34437301
- DOI: 10.1172/jci.insight.152403
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.
Keywords: Immunoglobulins; Infectious disease; Influenza.