作者: 屈泰龙 时间: 2015-12-7 21:25
刚看到，正要贴上来呢作者: rentianyixu 时间: 2015-12-7 21:41
Comprehensive analysis of antibody recognition in convalescent humans from highly pathogenic avian influenza H5N1 infection.
Zuo T1, Sun J2,3, Wang G4, Jiang L1, Zuo Y1, Li D1, Shi X1, Liu X2,3, Fan S2, Ren H4, Hu H4, Sun L5, Zhou B6, Liang M5, Zhou P4, Wang X2,3, Zhang L1.
Author information
1Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing 100084, China.
2Ministry of Education Key Laboratory of Protein Science, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
3Collaborative Innovation Center for Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
4Unit 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.
5State Key Laboratory for Infectious Disease Control and Prevention, National Institute for Viral Disease Control and Prevention, China CDC, Beijing 102206, China.
6Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen 518112, China.
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.
