A proof of concept for structure-based vaccine design targeting RSV in humans
A proof of concept for structure-based vaccine design targeting RSV in humans
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DOI：
10.1126/science.aav9033
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发表时间：
2019-08-02
期刊：
影响因子：
56.9
通讯作者：
Graham, Barney S.
中科院分区：
文献类型：
--
作者：
Crank, Michelle C.;Ruckwardt, Tracy J.;Graham, Barney S.
定义病毒表面蛋白上中和敏感表位的原子水平结构的技术正在改变疫苗学并指导新的疫苗开发方法。以前，进行了迭代的蛋白质工程以保留呼吸道合胞病毒（RSV）融合（F）糖蛋白的融合前构象，从而产生稳定的亚单位疫苗候选物（DS-Cav 1），其在小鼠和猕猴中显示出有希望的结果。在此，I期人体免疫原性数据显示，靶向RSV F融合前特异性表面的抗体在血清中的中和活性增强超过10倍。这些发现代表了基于结构的疫苗设计的概念的临床证明，表明开发成功的RSV疫苗是可行的，并预示着精确疫苗学的时代。
Technologies that define the atomic-level structure of neutralization-sensitive epitopes on viral surface proteins are transforming vaccinology and guiding new vaccine development approaches. Previously, iterative rounds of protein engineering were performed to preserve the prefusion conformation of the respiratory syncytial virus (RSV) fusion (F) glycoprotein, resulting in a stabilized subunit vaccine candidate (DS-Cav1), which showed promising results in mice and macaques. Here, phase I human immunogenicity data reveal a more than 10-fold boost in neutralizing activity in serum from antibodies targeting prefusion-specific surfaces of RSV F. These findings represent a clinical proof of concept for structure-based vaccine design, suggest that development of a successful RSV vaccine will be feasible, and portend an era of precision vaccinology.