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A multifunctional human monoclonal neutralizing antibody that targets a unique conserved epitope on influenza HA

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  • A multifunctional human monoclonal neutralizing antibody that targets a unique conserved epitope on influenza HA

    Nat Commun. 2018 Jul 10;9(1):2669. doi: 10.1038/s41467-018-04704-9.
    A multifunctional human monoclonal neutralizing antibody that targets a unique conserved epitope on influenza HA.

    Bangaru S1, Zhang H2,3, Gilchuk IM4, Voss TG4,5, Irving RP4, Gilchuk P4, Matta P4, Zhu X2, Lang S2, Nieusma T2, Richt JA6, Albrecht RA7, Vanderven HA8, Bombardi R4, Kent SJ8, Ward AB2, Wilson IA9,10, Crowe JE Jr11,12,13.
    Author information

    Abstract

    The high rate of antigenic drift in seasonal influenza viruses necessitates frequent changes in vaccine composition. Recent seasonal H3 vaccines do not protect against swine-origin H3N2 variant (H3N2v) strains that recently have caused severe human infections. Here, we report a human VH1-69 gene-encoded monoclonal antibody (mAb) designated H3v-47 that exhibits potent cross-reactive neutralization activity against human and swine H3N2 viruses that circulated since 1989. The crystal structure and electron microscopy reconstruction of H3v-47 Fab with the H3N2v hemagglutinin (HA) identify a unique epitope spanning the vestigial esterase and receptor-binding subdomains that is distinct from that of any known neutralizing antibody for influenza A H3 viruses. MAb H3v-47 functions largely by blocking viral egress from infected cells. Interestingly, H3v-47 also engages Fcγ receptor and mediates antibody dependent cellular cytotoxicity (ADCC). This newly identified conserved epitope can be used in design of novel immunogens for development of broadly protective H3 vaccines.


    PMID: 29991715 PMCID: PMC6039445 DOI: 10.1038/s41467-018-04704-9
    Free PMC Article
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