Abstract
Abstract H7N9 avian influenza virus causes severe infections in humans after cross-species transmission from bird reservoirs. Previous studies revealed that infection with H7N9 elicits a heterosubtypic polyclonal antibody (Ab) response between H7 and H3 or H1 hemagglutinins (HAs) in humans. However, relatively little is known about the functional activity, targeted epitopes, and breadth of reactivity of human monoclonal Abs (mAbs) against H7N9. In this study, we isolated 18 H7-reactive mAbs from survivors of natural H7N9 infection. The majority (14 of 18) of H7-reactive mAbs within the panel possessed neutralizing activity, mediated by inhibition of attachment or egress of the virus. Binding analysis of the isolated mAbs against fourteen influenza virus HAs representing group 1 and 2 revealed cross-reactivity for diverse strains within the H7 subtype and an extended response to H15 HA. Seven identified cross-reactive mAbs targeted the HA head domain, including neutralizing and non-neutralizing mAbs. Two neutralizing mAbs that are specific to the HA stem region revealed heterosubtypic reactivity against H7, H15 and H3 HAs. Further analysis identified the epitopes for heterosubtypic mAbs. This study provides insights into the basis for heterosubtypic antibody responses against H7N9 in human infection survivors and may inform efforts to incorporate novel epitope targets in broadly protective influenza vaccines.
Published Version
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