2. Academic Validation
  3. 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

  • Cell Host Microbe. 2017 Oct 11;22(4):471-483.e5. doi: 10.1016/j.chom.2017.08.011.
Fei Yu 1,  He Song 2,  Yanling Wu 3,  So Young Chang 4,  Lili Wang 3,  Wei Li 5,  Binbin Hong 3,  Shuai Xia 3,  Chunyu Wang 3,  Surender Khurana 6,  Yang Feng 5,  Yanping Wang 5,  Zhiwu Sun 3,  Biao He 3,  Dongni Hou 7,  Jody Manischewitz 6,  Lisa R King 6,  Yuanlin Song 7,  Ji-Young Min 4,  Hana Golding 6,  Xinhua Ji 2,  Lu Lu 3,  Shibo Jiang 3,  Dimiter S Dimitrov 5,  Tianlei Ying 8
Affiliations

Affiliations

  • 1 Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China; College of Life Sciences, Agricultural University of Hebei, Baoding, Hebei 071001, China.
  • 2 Macromolecular Crystallography Laboratory, National Cancer Institute, Frederick, MD 21702, USA.
  • 3 Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
  • 4 Respiratory Viruses Research Laboratory, Institut Pasteur Korea, Gyeonggi-do 463400, Republic of Korea.
  • 5 Protein Interactions Section, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.
  • 6 Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA.
  • 7 Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
  • 8 Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. Electronic address: [email protected].
PMID: 28966056 DOI: 10.1016/j.chom.2017.08.011
Abstract

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.

Keywords

ADCC; H7N9 influenza; germline; hemagglutinin; monoclonal antibody.

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