5 years ago

A Potent Germline-like Human Monoclonal Antibody Targets a pH-Sensitive Epitope on H7N9 Influenza Hemagglutinin

A Potent Germline-like Human Monoclonal Antibody Targets a pH-Sensitive Epitope on H7N9 Influenza Hemagglutinin
Tianlei Ying, Lisa R. King, Shuai Xia, Shibo Jiang, Fei Yu, Xinhua Ji, Hana Golding, Yanping Wang, Lili Wang, So Young Chang, Wei Li, Surender Khurana, Yanling Wu, Yang Feng, Dimiter S. Dimitrov, Ji-Young Min, Jody Manischewitz, He Song, Biao He, Chunyu Wang, Dongni Hou, Binbin Hong, Zhiwu Sun, Lu Lu, Yuanlin Song


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 Å) 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. 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.

Publisher URL: http://www.cell.com/cell-host-microbe/fulltext/S1931-3128(17)30344-X

DOI: 10.1016/j.chom.2017.08.011

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