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

Teng Zuo, Jianfeng Sun, Guiqin Wang, Liwei Jiang, Yanan Zuo, Danyang Li, Xuanling Shi, Xi Liu, Shilong Fan, Huanhuan Ren, Hongxing Hu, Lina Sun, Boping Zhou, Mifang Liang, Paul Zhou (), Xinquan Wang () and Linqi Zhang ()
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Teng Zuo: Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University
Jianfeng Sun: Ministry of Education Key Laboratory of Protein Science, Center for Structural Biology, School of Life Sciences, Tsinghua University
Guiqin Wang: Unit of Anti-Viral Immunity and Genetic Therapy, Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences
Liwei Jiang: Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University
Yanan Zuo: Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University
Danyang Li: Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University
Xuanling Shi: Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University
Xi Liu: Ministry of Education Key Laboratory of Protein Science, Center for Structural Biology, School of Life Sciences, Tsinghua University
Shilong Fan: Ministry of Education Key Laboratory of Protein Science, Center for Structural Biology, School of Life Sciences, Tsinghua University
Huanhuan Ren: Unit of Anti-Viral Immunity and Genetic Therapy, Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences
Hongxing Hu: Unit of Anti-Viral Immunity and Genetic Therapy, Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences
Lina Sun: State Key Laboratory for Infectious Disease Control and Prevention, National Institute for Viral Disease Control and Prevention, China CDC
Boping Zhou: Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People’s Hospital
Mifang Liang: State Key Laboratory for Infectious Disease Control and Prevention, National Institute for Viral Disease Control and Prevention, China CDC
Paul Zhou: Unit of Anti-Viral Immunity and Genetic Therapy, Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences
Xinquan Wang: Ministry of Education Key Laboratory of Protein Science, Center for Structural Biology, School of Life Sciences, Tsinghua University
Linqi Zhang: Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University

Nature Communications, 2015, vol. 6, issue 1, 1-14

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms9855

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