Department of Veterinary Pathobiology, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078, USA.
Department of Veterinary Sciences and Animal Husbandry, Chitradurga 577502, Karnataka, India.
Viruses. 2024 May 24;16(6):843. doi: 10.3390/v16060843.
Respiratory syncytial virus (RSV) is a major cause of severe respiratory tract disease worldwide, and a pediatric vaccine is not available. We generated a filamentous RSV-based virus-like particle (VLP) that presents the central conserved region of the attachment protein G. This was achieved by co-expressing the matrix protein, phosphoprotein, nucleoprotein, and a hybrid fusion protein in which the F ectodomain was replaced with the G central region (GCR). The latter is relatively conserved and contains a receptor binding site and hence is a logical vaccine target. The immunogenicity and efficacy of the resulting VLP, termed VLP-GCR, were examined in mice using intranasal application without adjuvant. VLP-GCR induced substantial anti-N antibody levels but very low anti-G antibody levels, even after three vaccinations. In contrast, a VLP presenting prefusion-stabilized fusion (preF) protein instead of GCR induced both high anti-F and anti-nucleoprotein antibody levels, suggesting that our GCR antigen was poorly immunogenic. Challenge of VLP-GCR-vaccinated mice caused increased weight loss and lung pathology, and both VLPs induced mucus in the lungs. Thus, neither VLP is suitable as a vaccine for RSV-naive individuals. However, VLP-preF enhanced the proportion of preF antibodies and could serve as a multi-antigen mucosal booster vaccine in the RSV-experienced population.
呼吸道合胞病毒（RSV）是全球严重呼吸道疾病的主要病因，目前尚无针对儿童的疫苗。我们构建了一种基于丝状 RSV 的病毒样颗粒（VLP），该 VLP 展示了附着蛋白 G 的中心保守区域。这是通过共表达基质蛋白、磷酸蛋白、核蛋白和一种融合蛋白来实现的，其中 F 结构域被 G 中心区域（GCR）取代。后者相对保守，包含受体结合位点，因此是一个合理的疫苗靶标。我们使用鼻内应用（无佐剂）在小鼠中检查了这种 VLP（称为 VLP-GCR）的免疫原性和功效。VLP-GCR 诱导了大量的抗-N 抗体水平，但抗-G 抗体水平非常低，即使进行了三次接种也是如此。相比之下，展示预融合稳定融合（preF）蛋白而不是 GCR 的 VLP 诱导了高水平的抗-F 和抗核蛋白抗体水平，表明我们的 GCR 抗原的免疫原性较差。用 VLP-GCR 疫苗接种的小鼠进行挑战导致体重减轻和肺部病理增加，两种 VLP 都在肺部引起粘液。因此，这两种 VLP 都不适合作为 RSV 初治个体的疫苗。然而，VLP-preF 增加了 preF 抗体的比例，可以作为 RSV 有经验人群的多抗原粘膜增强疫苗。
