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Human antibody recognition of H7N9 influenza virus HA following natural infection
Iuliia M. Gilchuk, … , Andrew B. Ward, James E. Crowe Jr.
Iuliia M. Gilchuk, … , Andrew B. Ward, James E. Crowe Jr.
Published August 26, 2021
Citation Information: JCI Insight. 2021;6(19):e152403. https://doi.org/10.1172/jci.insight.152403.
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Research Article Infectious disease

Human antibody recognition of H7N9 influenza virus HA following natural infection

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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 2 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 HA. 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 and B and in 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.

Authors

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

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Figure 1

Natural H7N9 influenza virus infection elicits HA-specific antibodies with broad reactivity within the H7 subtype, mainly targeting the head domain.

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Natural H7N9 influenza virus infection elicits HA-specific antibodies wi...
Cross-reactivity of antibodies to recombinant HA proteins from group 1 and 2 virus HA antigens as measured by ELISA. HAs were clustered by amino acid relatedness in the sequence phylogeny. (A) Dose-dependent HA antigen binding curves of serum samples from donors with naturally occurring laboratory-confirmed H7N9 infection (donors 957 and 958) or serum from control (an individual without exposure history to H7N9). Data are shown as mean ± SD of assay triplicates. (B) Heatmaps for cross-reactivity of polyclonal antibodies in convalescent serum samples from 2 H7N9 infection survivors or in negative control serum. Data represent the area under the curve for the binding assay. (C) Heatmaps for cross-reactivity of mAbs from the 2 survivors, isolated based on reactivity with the recombinant SH13 H7 HA antigen. Representative EC50 values (ng/mL) from 2 independent experiments are plotted. Three control mAbs are indicated by gray color. See also Supplemental Figure 1 and Supplemental Tables 1 and 2. ND, not determined.

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