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A cross-reactive human monoclonal antibody targets the conserved H7 antigenic site a from fifth wave H7N9-infected humans

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  • A cross-reactive human monoclonal antibody targets the conserved H7 antigenic site a from fifth wave H7N9-infected humans

    Antiviral Res. 2019 Jul 9:104556. doi: 10.1016/j.antiviral.2019.104556. [Epub ahead of print]
    A cross-reactive human monoclonal antibody targets the conserved H7 antigenic site a from fifth wave H7N9-infected humans.

    Li M1, Chen L1, Wang Q1, Hao M2, Zhang X1, Liu L3, Yu X3, Yang C1, Xu J4, Chen J5, Gong R6.
    Author information

    Abstract

    Subtype H7 avian influenza viruses have been found to be associated with human infection and represent a risk for global public health. In 2013, the emergence of H7N9 virus in human beings and persistent human infection in China raised the most serious pandemic threat. Here we identified a human monoclonal antibody, P52E03, targeting the hemagglutinin (HA) of subtype H7 influenza viruses (H7 antigen), from a convalescent patient infected with H7N9 in 2017. P52E03 showed in vitro hemagglutination inhibiting (HI) and neutralizing activity against subtype H7 viruses belonging to both North American and Eurasian lineages. Moreover, it could prophylactically protect mice against weight loss and death caused by challenge with lethal H7N9 viruses in vivo and, therefore, is a candidate for development of antiviral agent against H7N9 infection. By generating escape mutant variants, we found that a single G151E substitution in the viral H7 antigenic site A could abort the neutralizing activity. Computational structural prediction of the P52E03/H7 complex revealed that residues including G151 in and around the conserved antigenic A region are important for antigen recognition by the H7 cross-reactive antibody. Finally, we found that the P52E03 germline precursor (gHgL) antibody recognizes HA with measurable affinity, suggesting that its epitope is vulnerable to the human immune system and might elicit neutralizing antibodies (nAbs) in vivo after vaccination.
    Copyright 2019. Published by Elsevier B.V.


    KEYWORDS:

    Antibody; Epitope; H7N9; Hemagglutination inhibiting; Influenza virus; Neutralizing

    PMID: 31299269 DOI: 10.1016/j.antiviral.2019.104556
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