title: Comprehensive analysis of antibody recognition in convalescent humans from highly pathogenic avian influenza H5N1 infection.
abstract: Understanding the mechanism of protective antibody recognition against highly pathogenic avian influenza A virus H5N1 in humans is critical for the development of effective therapies and vaccines. Here we report the crystal structure of three H5-specific human monoclonal antibodies bound to the globular head of hemagglutinin (HA) with distinct epitope specificities, neutralization potencies and breadth. A structural and functional analysis of these epitopes combined with those reported elsewhere identifies four major vulnerable sites on the globular head of H5N1 HA. Chimeric and vulnerable site-specific mutant pseudoviruses are generated to delineate broad neutralization specificities of convalescent sera from two individuals who recovered from the infection with H5N1 virus. Our results show that the four vulnerable sites on the globular head rather than the stem region are the major neutralizing targets, suggesting that during natural H5N1 infection neutralizing antibodies against the globular head work in concert to provide protective antibody-mediated immunity.
authors.affiliation: Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Zuo
authors.affiliation: Ministry of Education Key Laboratory of Protein Science, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.|Collaborative Innovation Center for Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Sun
authors.affiliation: Unit of Anti-Viral Immunity and Genetic Therapy, Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Guiqin
authors.initials: G
authors.lastname: Wang
authors.affiliation: Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Liwei
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Zuo
authors.affiliation: Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Danyang
authors.initials: D
authors.lastname: Li
authors.affiliation: Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Xuanling
authors.initials: X
authors.lastname: Shi
authors.affiliation: Ministry of Education Key Laboratory of Protein Science, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.|Collaborative Innovation Center for Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Liu
authors.affiliation: Ministry of Education Key Laboratory of Protein Science, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Shilong
authors.initials: S
authors.lastname: Fan
authors.affiliation: Unit of Anti-Viral Immunity and Genetic Therapy, Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Ren
authors.affiliation: Unit of Anti-Viral Immunity and Genetic Therapy, Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Hongxing
authors.initials: H
authors.lastname: Hu
authors.affiliation: State Key Laboratory for Infectious Disease Control and Prevention, National Institute for Viral Disease Control and Prevention, China CDC, Beijing 102206, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Sun
authors.affiliation: Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen 518112, China.
authors.forename: Boping
authors.initials: B
authors.lastname: Zhou
authors.affiliation: State Key Laboratory for Infectious Disease Control and Prevention, National Institute for Viral Disease Control and Prevention, China CDC, Beijing 102206, China.
authors.forename: Mifang
authors.initials: M
authors.lastname: Liang
authors.affiliation: Unit of Anti-Viral Immunity and Genetic Therapy, Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Paul
authors.initials: P
authors.lastname: Zhou
authors.affiliation: Ministry of Education Key Laboratory of Protein Science, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.|Collaborative Innovation Center for Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
authors.forename: Xinquan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Linqi
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000737:chemistry / Q000276:immunology; D000914:Antibodies, Viral / Q000737:chemistry / Q000276:immunology*; D001717:Birds; D018604:Epitope Mapping; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D005585:Influenza in Birds / Q000821:virology; D007251:Influenza, Human / Q000276:immunology* / Q000821:virology; D008297:Male; D017434:Protein Structure, Tertiary; D014774:Virulence
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus