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Nature:清华大学和中科院上海巴斯德研究发现可以为H5N1疫苗研发提供精准靶标

摘要 : 日前,清华大学和中科院上海巴斯德研究所科研人员合作,在高致病性禽流感病毒H5N1康复者体内抗体识别和保护机制方面取得进展,相关成果发布于《自然—通讯》。这是国际上首次对高致病性禽流感病毒H5N1人源单克隆中和抗体和康复者体内多克隆抗体进行系统结构与功能研究,为高效流感疫苗和治疗性抗体的研发提供了精准的靶标。

日前,清华大学和中科院上海巴斯德研究所科研人员合作,在高致病性禽流感病毒H5N1康复者体内抗体识别和保护机制方面取得进展,相关成果发布于《自然—通讯》。这是国际上首次对高致病性禽流感病毒H5N1人源单克隆中和抗体和康复者体内多克隆抗体进行系统结构与功能研究,为高效流感疫苗和治疗性抗体的研发提供了精准的靶标。

前期的研究结果表明,季节性流感病毒HA是保护性抗体识别的关键组成部分。但是,科学家对高致病性禽流感H5N1感染者体内保护性抗体识别的靶点、结构与功能特征知之甚少。本次研究中,科研人员对高致病性禽流感病毒H5N1康复者体内的抗体反应进行了系统评估。在获得5株来源于康复者单克隆抗体的基础上,利用酵母表面展示技术、基因定点突变技术、结构生物学和生物信息学技术,综合总结和首次定义了H5血凝素蛋白头部的4个关键薄弱位点。

科研人员进一步利用重组病毒技术,证明康复者血清中多克隆抗体识别主要针对这4个薄弱位点,而非位于H5血凝素蛋白颈部HA2的其它位点。

原文链接:

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

原文摘要: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 elsewher 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.

来源: Nature 浏览次数:0

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