Comprehensive analysis of antibody recognition in convalescent humans from highly pathogenic avian influenza H5N1 infection

被引:38
作者
Zuo, Teng [1 ]
Sun, Jianfeng [2 ,3 ,4 ]
Wang, Guiqin [5 ]
Jiang, Liwei [1 ]
Zuo, Yanan [1 ]
Li, Danyang [1 ]
Shi, Xuanling [1 ]
Liu, Xi [2 ,3 ,4 ]
Fan, Shilong [2 ]
Ren, Huanhuan [5 ]
Hu, Hongxing [5 ]
Sun, Lina [6 ]
Zhou, Boping [7 ]
Liang, Mifang [6 ]
Zhou, Paul [5 ]
Wang, Xinquan [2 ,3 ,4 ]
Zhang, Linqi [1 ]
机构
[1] Tsinghua Univ, Sch Med, Collaborat Innovat Ctr Diag & Treatment Infect Di, Comprehens AIDS Res Ctr, Beijing 100084, Peoples R China
[2] Tsinghua Univ, Minist Educ, Struct Biol Ctr, Sch Life Sci,Key Lab Prot Sci, Beijing 100084, Peoples R China
[3] Sichuan Univ, Collaborat Innovat Ctr Biotherapy, State Key Lab Biotherapy, West China Hosp,West China Med Sch, Chengdu 610041, Peoples R China
[4] Sichuan Univ, Ctr Canc, West China Med Sch, West China Hosp, Chengdu 610041, Peoples R China
[5] Chinese Acad Sci, Inst Pasteur Shanghai, Unit Antiviral Immun & Genet Therapy, Key Lab Mol Virol & Immunol, Shanghai 200031, Peoples R China
[6] China CDC, Natl Inst Viral Dis Control & Prevent, State Key Lab Infect Dis Control & Prevent, Beijing 102206, Peoples R China
[7] Shenzhen Third Peoples Hosp, Shenzhen Key Lab Pathogen & Immun, Shenzhen 518112, Peoples R China
基金
美国国家卫生研究院;
关键词
A H5N1; VIRUS-INFECTION; ANTIGENIC STRUCTURE; HEMAGGLUTININ; NEUTRALIZATION; EPITOPE; TRANSMISSION; VACCINE; PROTECTION; RESPONSES;
D O I
10.1038/ncomms9855
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
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页数:12
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