机构：[1]Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing 100084, China.[2]Ministry of Education Key Laboratory of Protein Science, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.[3]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.四川大学华西医院[4]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.[5]State Key Laboratory for Infectious Disease Control and Prevention, National Institute for Viral Disease Control and Prevention, China CDC, Beijing 102206, China.[6]Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People’s Hospital, Shenzhen 518112, China.[7]Genome Biology Unit, European Molecular Biology Laboratory, Meyerhofstrasse, Heidelberg 169117, Germany.
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.
基金：
This work was supported by the funds from National Natural Science Foundation Award
81530065, 81101236 and U1405228, Ministry of Science and Technology of China
(2014CB542500-03 and 2011CB910502), the National Science and Technology Major
Projects (2009ZX10004-016 and 2012ZX10001-008), the 863 Project (#2012AA02A404-
07) and the Li Kai-Shing Foundation of Hong Kong. The work is also partially supported
by US National Institutes of Health CIPRA Grant (U19 AI51915) and Janssen Investigator Award to Linqi Zhang and Xinquan Wang. We acknowledge the China
National Center for Protein Sciences (Beijing) and the Shanghai Synchrotron Research
Facility (SSRF) beam line BL17U for providing the facility support.
第一作者机构：[1]Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing 100084, China.
共同第一作者：
通讯作者：
通讯机构：[2]Ministry of Education Key Laboratory of Protein Science, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.[3]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.
推荐引用方式(GB/T 7714)：
Teng Zuo,Jianfeng Sun,Guiqin Wang,et al.Comprehensive analysis of antibody recognition in convalescent humans from highly pathogenic avian influenza H5N1 infection.[J].NATURE COMMUNICATIONS.2015,6:doi:10.1038/ncomms9855.
APA：
Teng Zuo,Jianfeng Sun,Guiqin Wang,Liwei Jiang,Yanan Zuo...&Linqi Zhang.(2015).Comprehensive analysis of antibody recognition in convalescent humans from highly pathogenic avian influenza H5N1 infection..NATURE COMMUNICATIONS,6,
MLA：
Teng Zuo,et al."Comprehensive analysis of antibody recognition in convalescent humans from highly pathogenic avian influenza H5N1 infection.".NATURE COMMUNICATIONS 6.(2015)
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