Frey Steven J, Varner Chad, Arsiwala Ammar, Currier Michael G, Moore Martin L, Kane Ravi S
School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, 30332, USA.
Department of Pediatrics, Emory University, Atlanta, GA, 30322, USA.
Adv Healthc Mater. 2021 Feb;10(4):e2000714. doi: 10.1002/adhm.202000714. Epub 2020 Aug 5.
Respiratory syncytial virus (RSV), for which there is currently no licensed vaccine, displays a fusion (F) protein that is considered a vaccine target. This protein has an antigenic site called site Ø, which has been shown to elicit potent, neutralizing antibodies and has therefore been considered important in the formulation of RSV vaccines. However, this site is also the least conserved region on the F protein across RSV subtypes. Therefore, directing the immune response away from site Ø and refocusing it toward more conserved parts of the RSV F protein might serve to better elicit broadly neutralizing antibodies. To demonstrate that directing the immune response away from site Ø is a viable approach, a prefusion F-based vaccine based on an F protein with a shielded site Ø is generated. Sera from mice immunized with multivalent scaffolds presenting this immunogen is capable of neutralizing RSV of both subtypes. This result may have application in the development of an effective and broadly protective RSV vaccine.
呼吸道合胞病毒（RSV）目前尚无获批疫苗，其融合（F）蛋白被视为疫苗靶点。该蛋白有一个名为位点Ø的抗原位点，已证明该位点可引发强效中和抗体，因此在RSV疫苗配方中被认为很重要。然而，该位点也是RSV各亚型F蛋白上保守性最低的区域。因此，引导免疫反应远离位点Ø，使其重新聚焦于RSV F蛋白更保守的部分，可能有助于更好地引发广泛中和抗体。为证明引导免疫反应远离位点Ø是一种可行的方法，制备了一种基于具有屏蔽位点Ø的F蛋白的预融合F疫苗。用呈现这种免疫原的多价支架免疫的小鼠血清能够中和两种亚型的RSV。这一结果可能在开发有效且具有广泛保护作用的RSV疫苗中具有应用价值。
