The H7N9 influenza virus causes high-mortality disease in humans but no effective therapeutics are available. Here we report a novel human monoclonal antibody, m826, which bound to H7 hemagglutinin (HA) with subnanomolar affinity at pH 5.0 and 10-fold lower affinity at neutral pH. The high-resolution (1.9 Å) crystal structure of m826 complexed with H7N9 HA indicated that m826 binds to a novel unique epitope which could explain its pH sensitivity. Furthermore, m826 fully protected mice against lethal challenge of H7N9 virus, indicating that m826 is highly effective in vivo likely due to its ability to induce potent ADCC. Interestingly, immunogenetic analysis indicated that m826 is a germline antibody and m826-like sequences can be identified in H7N9-infected patients, healthy adults and newborn babies. The unique m826 properties offer a template for H7N9 vaccine immunogens, a promising candidate therapeutic, and a new tool for exploring mechanisms of virus infection inhibition by antibodies.
Yu, Fei and Song, He and Wu, Yanling and Chang, So Young and Wang, Lili and Xia, Shuai and Hong, Binbin and Li, Wei and Wang, Chunyu and Khurana, Surender and Feng, Yang and Wang, Yanping and Sun, Zhiwu and He, Biao and Manischewitz, Jody and King, Lisa R. and Min, Ji-Young and Golding, Hana and Ji, Xinhua and Lu, Lu and Jiang, Shibo and Dimitrov, Dimiter S. and Ying, Tianlei, A Potent Germline-Like Human Monoclonal Antibody Targeting a Novel pH-Sensitive Epitope on H7N9 Influenza Hemagglutinin (2018). Available at SSRN: https://ssrn.com/abstract=3155911 or http://dx.doi.org/10.2139/ssrn.3155911
This version of the paper has not been formally peer reviewed.