美国国立卫生研究院Barney S. Graham团队的一项最新研究，验证了利用结构设计人RSV疫苗的可行性。这一研究成果于2019年8月2日发表在国际学术期刊《科学》上。

为了保持呼吸道合胞病毒（RSV）融合（F）糖蛋白的融合前构象，研究人员经过反复几轮的蛋白工程，得到了一个稳定亚基的候选疫苗(DS-Cav1)，并在小鼠和猕猴实验中表现出有前景的结果。研究人员在一期人类免疫原性数据中发现，针对RSV F蛋白融合前特异性表面的抗体在血清中的中和活力超过了10倍的增加。这些发现为基于结构的疫苗设计提供了临床上的概念证明，并提示研发成功的RSV疫苗是可行的，此外也预示着精确疫苗学时代的到来。

据悉，病毒表面的蛋白存在中和敏感的抗原表位，在原子水平解这些结构的技术，正在改变疫苗学，并指导新的疫苗开发方法。

附：英文原文

Title: A proof of concept for structure-based vaccine design targeting RSV in humans

Author: Michelle C. Crank, Tracy J. Ruckwardt, Man Chen, Kaitlyn M. Morabito, Emily Phung, Pamela J. Costner, LaSonji A. Holman, Somia P. Hickman, Nina M. Berkowitz, Ingelise J. Gordon, Galina V. Yamshchikov, Martin R. Gaudinski, Azad Kumar, Lauren A. Chang, Syed M. Moin, Juliane P. Hill, Anthony T. DiPiazza, Richard M. Schwartz, Lisa Kueltzo, Jonathan W. Cooper, Peifeng Chen, Judith A. Stein, Kevin Carlton, Jason G. Gall, Martha C. Nason, Peter D. Kwong, Grace L. Chen, John R. Mascola, Jason S. McLellan, Julie E. Ledgerwood, Barney S. Graham, the VRC Study Team

Issue&Volume: Vol 365 Issue 6452

Abstract: 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.

DOI: 10.1126/science.aav9033

Source:https://science.sciencemag.org/content/365/6452/505