Respiratory syncytial virus (RSV) is a serious respiratory pathogen in infants and young children worldwide. Currently, no licensed RSV vaccines are available. In this study, we explored stable prefusion conformation virus-like particles (Pre-F VLPs) as RSV vaccine candidates. RSV fusion (F) protein mutants were constructed to form stabilized Pre-F or postfusion (Post-F) configurations. VLPs containing Pre-F or Post-F protein were generated using a recombinant baculovirus (rBV)-insect cell expression system. The assembly and immunological properties of Pre-F or Post-F VLPs were investigated. Pre-F and Post-F VLPs contained antigenic sites Ø and I of pre- and postfusion conformations, respectively. Compared with Post-F VLPs, immunization with Pre-F VLPs elicited upregulation of IFN-γ, IL-2 and IL-10 and downregulation of IL-4 and IL-5 cytokine production in mice. A high percentage of CD25+ Foxp3+ cells or a low percentage of IL-17A-producing cells among CD4+ T cells was observed in the lungs of mice vaccinated with Pre-F VLPs. Importantly, immunization with Pre-F VLPs induced a high level of RSV neutralizing antibody and a balanced immune response, which protected mice against RSV infection without evidence of immunopathology. Our results suggested that Pre-F VLPs generated from rBV-insect cells represent promising RSV vaccine candidates.

中文翻译：

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含有预融合稳定 F 蛋白的病毒样颗粒可诱导平衡的免疫反应并赋予小鼠抗呼吸道合胞病毒感染的保护作用

呼吸道合胞病毒 (RSV) 是全世界婴幼儿的一种严重呼吸道病原体。目前，没有获得许可的 RSV 疫苗。在这项研究中，我们探索了稳定的融合前构象病毒样颗粒 (Pre-F VLP) 作为 RSV 候选疫苗。构建 RSV 融合 (F) 蛋白突变体以形成稳定的 Pre-F 或融合后 (Post-F) 配置。使用重组杆状病毒 (rBV)-昆虫细胞表达系统生成含有 Pre-F 或 Post-F 蛋白的 VLP。研究了 Pre-F 或 Post-F VLP 的组装和免疫学特性。Pre-F 和 Post-F VLP 分别包含融合前和融合后构象的抗原位点 Ø 和 I。与 Post-F VLP 相比，用 Pre-F VLP 免疫引起 IFN-γ 的上调，小鼠中 IL-2 和 IL-10 以及 IL-4 和 IL-5 细胞因子产生的下调。高百分比的CD25+Foxp3+细胞或 CD4 中产生 IL-17A 的细胞百分比较低+在接种 Pre-F VLP 的小鼠肺部观察到了 T 细胞。重要的是，用 Pre-F VLPs 免疫诱导了高水平的 RSV 中和抗体和平衡的免疫反应，这在没有免疫病理学证据的情况下保护小鼠免受 RSV 感染。我们的结果表明，由 rBV 昆虫细胞产生的 Pre-F VLP 代表了有希望的 RSV 候选疫苗。