Zuo Teng, Sun Jianfeng, Wang Guiqin, Jiang Liwei, Zuo Yanan, Li Danyang, Shi Xuanling, Liu Xi, Fan Shilong, Ren Huanhuan, Hu Hongxing, Sun Lina, Zhou Boping, Liang Mifang, Zhou Paul, Wang Xinquan, Zhang Linqi
Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing 100084, China.
Ministry of Education Key Laboratory of Protein Science, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Nat Commun. 2015 Dec 4;6:8855. doi: 10.1038/ncomms9855.
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.
了解人类针对高致病性甲型H5N1禽流感病毒的保护性抗体识别机制对于开发有效的治疗方法和疫苗至关重要。在此，我们报告了三种H5特异性人单克隆抗体与血凝素（HA）球状头部结合的晶体结构，这些抗体具有不同的表位特异性、中和效力和广度。对这些表位进行的结构和功能分析，结合其他地方报道的结果，确定了H5N1 HA球状头部的四个主要易损位点。构建了嵌合型和位点特异性突变假病毒，以描绘两名从H5N1病毒感染中康复的个体恢复期血清的广泛中和特异性。我们的结果表明，球状头部而非茎区的四个易损位点是主要的中和靶点，这表明在自然H5N1感染期间，针对球状头部的中和抗体协同发挥作用，提供保护性抗体介导的免疫。
