Selected article for: "crystal structure and high resolution"
Author: Yu, Fei; Song, He; Wu, Yanling; Young Chang, So; Wang, Lili; Li, Wei; Hong, Binbin; Xia, Shuai; Wang, Chunyu; Khurana, Surender; Feng, Yang; Wang, Yanping; Sun, Zhiwu; He, Biao; Hou, Dongni; Manischewitz, Jody; King, Lisa R.; Song, Yuanlin; Min, Ji-Young; Golding, Hana; Ji, Xinhua; Lu, Lu; Jiang, Shibo; Dimitrov, Dimiter S.; Ying, Tianlei
Title: A potent germline-like human monoclonal antibody targets a pH-sensitive epitope on H7N9 influenza hemagglutinin
  • Cord-id: 0bqpzwuq
  • Document date: 2017_10_1
    • ID: 0bqpzwuq
    Snippet: The H7N9 influenza virus causes high-mortality disease in humans but no effective therapeutics are available. Here we report a human monoclonal antibody, m826, that binds to H7 hemagglutinin (HA) and protects against H7N9 infection. m826 binds to H7N9 HA with subnanomolar affinity at acidic pH and 10-fold lower affinity at neutral pH. The high-resolution (1.9 Ã…) crystal structure of m826 complexed with H7N9 HA indicates that m826 binds an epitope that may be fully exposed upon pH-induced confor
    Document: The H7N9 influenza virus causes high-mortality disease in humans but no effective therapeutics are available. Here we report a human monoclonal antibody, m826, that binds to H7 hemagglutinin (HA) and protects against H7N9 infection. m826 binds to H7N9 HA with subnanomolar affinity at acidic pH and 10-fold lower affinity at neutral pH. The high-resolution (1.9 Ã…) crystal structure of m826 complexed with H7N9 HA indicates that m826 binds an epitope that may be fully exposed upon pH-induced conformational changes in HA. m826 fully protects mice against lethal challenge with H7N9 virus through mechanisms likely involving antibody-dependent cell-mediated cytotoxicity (ADCC). Interestingly, immunogenetic analysis indicates that m826 is a germline antibody and m826-like sequences can be identified in H7N9-infected patients, healthy adults and newborn babies. These m826 properties offer a template for H7N9 vaccine immunogens, a promising candidate therapeutic, and a tool for exploring mechanisms of virus infection inhibition by antibodies.

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