title: Human antibody 3E1 targets the HA stem region of H1N1 and H5N6 influenza A viruses.
abstract: As influenza A viruses remain a major threat to human health worldwide, the discovery of broadly neutralizing monoclonal antibodies that recognize conserved epitopes would facilitate the development of antibody-based therapeutic strategies. Here we report that a VH4-4-encoded human mAb named 3E1 could neutralize H1 and H5 subtype viruses in vitro and protect mice against the H1N1 and H5N6 viruses by inhibiting the low pH-induced conformational rearrangement of haemagglutinin (HA), hence blocking membrane fusion. The crystal structures of 3E1 Fab in complex with HA of two H1N1 strains reveal that 3E1, with both heavy and light chains, binds to a conserved epitope of the HA stem region, comprising parts of the fusion peptide, the F subdomain and the outermost β-strand preceding helix A. Altogether, these data suggest the potential of 3E1 as a therapeutic drug against H1 and H5 subtype viruses.
authors.affiliation: National Center for Protein Science Shanghai, State Key Laboratory of Molecular Biology, Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences and University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
authors.forename: Wenshuai
authors.initials: W
authors.lastname: Wang
authors.affiliation: CAS Key Laboratory of Molecular Virology &Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, China.
authors.forename: Yanbing
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
authors.forename: Jinpeng
authors.initials: J
authors.lastname: Su
authors.affiliation: State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
authors.forename: Zhiyang
authors.initials: Z
authors.lastname: Ling
authors.affiliation: National Center for Protein Science Shanghai, State Key Laboratory of Molecular Biology, Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences and University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
authors.forename: Tianlong
authors.initials: T
authors.lastname: Zhang
authors.affiliation: National Center for Protein Science Shanghai, State Key Laboratory of Molecular Biology, Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences and University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: CAS Key Laboratory of Molecular Virology &Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, China.
authors.forename: Hualan
authors.initials: H
authors.lastname: Chen
authors.affiliation: National Center for Protein Science Shanghai, State Key Laboratory of Molecular Biology, Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences and University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.|Shanghai Science Research Center, Chinese Academy of Sciences, Shanghai 201204, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Ding
authors.affiliation: CAS Key Laboratory of Molecular Virology &Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.|State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Sun
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology*; D000915:Antibody Affinity; D000939:Epitopes / Q000737:chemistry / Q000378:metabolism; D005260:Female; D057809:HEK293 Cells; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D009980:Influenza A virus / Q000145:classification / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control / Q000662:veterinary*; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000939:Epitopes; D019267:Hemagglutinin Glycoproteins, Influenza Virus