2012年1月12日，国际著名病毒学杂志Journal of Virology 在线刊登了上海巴斯德研究所周保罗研究组的最新研究成果“A Human Antibody Recognizing a Conserved Epitope of H5 Hemagglutinin Broadly Neutralizes Highly Pathogenic Avian Influenza H5N1 Viruses，”，这是首例关于人的中和抗体可以广谱中和几乎所有的H5N1各个型和亚型病毒的报道。
自1996年以来，高致病性禽流感H5N1病毒感染了超过5亿家禽，并且在亚洲、非洲和欧洲出现了越来越多关于人感染H5N1病毒的报道。至2011年10月10日，已有566例人感染被确诊，其中332人死亡(http：//www.who.int/csr/disease/avian_influenza/country/en/)。目前的疫苗往往只对相似的病毒株有保护作用。
在这项研究中，上海巴斯德所的博士生胡红星等人在周保罗教授的指导下用高灵敏度的H5N1假病毒系统从感染过H5N1病毒但康复的病人记忆B细胞中筛选出了3株抗H5N1病毒的人源单克隆抗体。其中单克隆抗体65C6 能够中和除了7.2亚型之外几乎所有型和亚型的H5N1 病毒，并在老鼠模型中显示了很好的预防和保护的作用。通过对血凝蛋白和抗体复合物的电镜分析，结合酵母展示技术，研究人员发现单克隆抗体65C6能够识别位于血凝蛋白球形头部的构象表位。该表位在几乎所有的H5N1的血凝蛋白上都是高度保守的。提示该广谱中和抗体可以用来治疗感染了高致病性禽流感H5N1的病人，另外基于该保守表位可以设计免疫原从而通过免疫诱导出针对该表位的抗高致病性禽流感H5N1的广谱中和抗体反应。
该课题是与英国国立医学研究院的John Skehel 教授及柬埔寨巴斯德研究所的Vincent Deubel教授，清华大学的张林琦教授以及深圳第三人民医院的周伯平教授合作完成的。
该研究得到了法国卫生部、国家自然科学基金、国家科技重大专项及李嘉诚基金会和英国医学研究基金会的资助。（生物谷Bioon.com）
doi:10.1128/JVI.06665-11
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A Human Antibody Recognizing a Conserved Epitope of H5 Hemagglutinin Broadly Neutralizes Highly Pathogenic Avian Influenza H5N1 Viruses
Hongxing Hu1, Jarrod Voss2, Guoliang Zhang3, Philippi Buchy4, Teng Zuo5, Lulan Wang1, Feng Wang1, Fan Zhou1, Guiqing Wang1, Cheguo Tsai1, Lesley Calder2, Steve J. Gamblin2, Linqi Zhang5, Vincent Deubel4, Boping Zhou3, John J. Skehel2↴ and Paul Zhou1↴
Influenza A virus infection is a persistent threat to public health worldwide, due to its ability to evade immune surveillance through rapid genetic drift and shift. Current vaccines against influenza A virus provide immunity to viral isolates similar to vaccine strains. High affinity neutralizing antibodies against conserved epitopes could provide immunity to diverse influenza strains and protection against future pandemic viruses. In this study, by using a highly sensitive H5N1 pseudotype-based neutralization assay to screen human monoclonal antibodies produced by memory B cells from a H5N1 infected individual and molecular cloning techniques, we developed three fully human monoclonal antibodies. Among them, antibody 65C6 exhibited potent neutralization activity against all H5 clades and subclades except for subclade 7.2 and prophylactic and therapeutic efficacy against highly pathogenic avian influenza H5N1 viruses in mice. Studies on HA-antibody complexes by electron microscopy and epitope mapping indicate that antibody 65C6 binds to a conformational epitope comprising amino acid residues at the positions of 118, 121, 161, 164 and 167 (according to mature H5 numbering) on the tip of the membrane-distal globular domain of HA. Thus, we conclude that antibody 65C6 recognizes a neutralization epitope in the globular head of HA that is conserved among almost all divergent H5N1 influenza stains.
