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Cell Host&Microbe: Both Neutralizing and Non-Neutralizing Human H7N9 Influenza Vaccine-Induced Monoclonal Antibodies Confer Protection

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  • Cell Host&Microbe: Both Neutralizing and Non-Neutralizing Human H7N9 Influenza Vaccine-Induced Monoclonal Antibodies Confer Protection

    • Both Neutralizing and Non-Neutralizing Human H7N9 Influenza Vaccine-Induced Monoclonal Antibodies Confer Protection

      Carole J. Henry Dunand10
      , Paul E. Leon10
      , Min Huang
      , Angela Choi
      , Veronika Chromikova
      , Irvin Y. Ho
      , Gene S. Tan
      , John Cruz
      , Ariana Hirsh
      , Nai-Ying Zheng
      , Caitlin E. Mullarkey
      , Francis A. Ennis
      , Masanori Terajima
      , John J. Treanor
      , David J. Topham
      , Kanta Subbarao
      , Peter Palese
      , Florian Krammer
      , Patrick C. Wilson
    • ?Generation and characterization of human monoclonal antibodies after H7N9 vaccination
    • ?Neutralizing and non-neutralizing protective antibodies are induced by H7N9 vaccine
    • ?Neutralizing antibodies target known and novel epitopes on the hemagglutinin protein
    • ?Non-neutralizing antibodies mediate protection through Fc-FcγR interactions


    Summary

    Pathogenic H7N9 avian influenza viruses continue to represent a public health concern, and several candidate vaccines are currently being developed. It is vital to assess if protective antibodies are induced following vaccination and to characterize the diversity of epitopes targeted. Here we characterized the binding and functional properties of twelve H7-reactive human antibodies induced by a candidate A/Anhui/1/2013 (H7N9) vaccine. Both neutralizing and non-neutralizing antibodies protected mice in vivo during passive transfer challenge experiments. Mapping the H7 hemagglutinin antigenic sites by generating escape mutant variants against the neutralizing antibodies identified unique epitopes on the head and stalk domains. Further, the broadly cross-reactive non-neutralizing antibodies generated in this study were protective through Fc-mediated effector cell recruitment. These findings reveal important properties of vaccine-induced antibodies and provide a better understanding of the human monoclonal antibody response to influenza in the context of vaccines.



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