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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.
Pubmed ID: 28966056 RIS Download
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A high-quality integrated knowledge resource specialized in the immunoglobulins (IG) or antibodies, T cell receptors (TR), major histocompatibility complex (MHC) of human and other vertebrate species, and in the immunoglobulin superfamily (IgSF), MHC superfamily (MhcSF) and related proteins of the immune system (RPI) of vertebrates and invertebrates, serving as the global reference in immunogenetics and immunoinformatics. IMGT provides a common access to sequence, genome and structure Immunogenetics data, based on the concepts of IMGT-ONTOLOGY and on the IMGT Scientific chart rules. IMGT works in close collaboration with EBI (Europe), DDBJ (Japan) and NCBI (USA). IMGT consists of sequence databases, genome database, structure database, and monoclonal antibodies database, Web resources and interactive tools.
View all literature mentionsCrystallographic software which solves structures using algorithms and automated rapid search calculations to perform molecular replacement and experimental phasing methods.
View all literature mentionsA Python-based software suite for the automated determination of molecular structures using X-ray crystallography and other methods. Phenix includes programs for assessing data quality, experimental phasing, molecular replacement, model building, structure refinement, and validation. It also includes tools for reflection data and creating maps and models. Phenix can also be used for neutron crystallography. Tutorials and examples are available in the documentation tab.
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