Division of Pediatric Infectious Diseases, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA 30322, USA.
Department of Biochemistry, University of Wisconsin, Madison, WI 53706, USA.
Viruses. 2020 Aug 19;12(9):906. doi: 10.3390/v12090906.
Respiratory syncytial virus (RSV) causes substantial lower respiratory tract disease in children and at-risk adults. Though there are no effective anti-viral drugs for acute disease or licensed vaccines for RSV, palivizumab prophylaxis is available for some high risk infants. To support anti-viral and vaccine development efforts, we developed an RSV virus-like particle (VLP) platform to explore the role RSV F and G protein interactions in disease pathogenesis. Since VLPs are immunogenic and a proven platform for licensed human vaccines, we also considered these VLPs as potential vaccine candidates. We developed two RSV VLP platforms, M+P and M+M2-1 that had F and G, F and a G peptide, or a truncated F and G on their surface. Immunoblots of sucrose gradient purified particles showed co-expression of M, G, and F with both VLP platforms. Electron microscopy imaging and immunogold labeling confirmed VLP-like structures with surface exposed projections consistent with F and G proteins. In mice, the VLPs induced both anti-F and -G protein antibodies and, on challenge, reduced lung viral titer and inflammation. These data show that these RSV VLP platforms provide a tool to study the structure of F and G and their interactions and flexible platforms to develop VLP vaccines in which all components contribute to RSV-specific immune responses.
呼吸道合胞病毒（RSV）可导致儿童和高危成年人发生严重的下呼吸道疾病。虽然目前尚无针对急性疾病的有效抗病毒药物或 RSV 疫苗，但某些高危婴儿可使用帕利珠单抗进行预防。为了支持抗病毒和疫苗开发工作，我们开发了一种 RSV 病毒样颗粒（VLP）平台，以研究 RSV F 和 G 蛋白相互作用在疾病发病机制中的作用。由于 VLP 具有免疫原性，并且是经过验证的已许可人类疫苗平台，因此我们也将这些 VLP 视为潜在的疫苗候选物。我们开发了两种 RSV VLP 平台，M+P 和 M+M2-1，它们在表面上具有 F 和 G、F 和 G 肽或截短的 F 和 G。蔗糖梯度纯化颗粒的免疫印迹显示，两种 VLP 平台均能共同表达 M、G 和 F。电子显微镜成像和免疫金标记证实了具有表面暴露突起的 VLP 样结构，这些突起与 F 和 G 蛋白一致。在小鼠中，VLP 诱导了抗 F 和抗 G 蛋白抗体，在受到挑战时，降低了肺部病毒滴度和炎症。这些数据表明，这些 RSV VLP 平台为研究 F 和 G 的结构及其相互作用提供了工具，并且为开发 VLP 疫苗提供了灵活的平台，其中所有成分都有助于 RSV 特异性免疫反应。
