Laboratory of Nano-design for Innovative Drug Development, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan; Vaccine Creation Group, Research Institute for Microbial Diseases, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan.
The Research Foundation for Microbial Diseases of Osaka University, 3-1 Yamadaoka, Suita, Osaka, 565-0871, Japan; Institute for Open and Transdisciplinary Research Initiatives, Osaka University, 3-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Biochem Biophys Res Commun. 2023 Dec 17;686:149143. doi: 10.1016/j.bbrc.2023.149143. Epub 2023 Oct 26.
Respiratory syncytial virus (RSV) is a leading cause of severe respiratory illness worldwide, particularly in infants and older adults. Vaccines targeting the fusion glycoprotein (F protein) -one of the surface antigens of RSV- are highly effective in preventing RSV-associated severe lower respiratory tract disease. However, the efficacy of these vaccines against upper respiratory tract challenge needs improvement. Here, we aimed to examine the efficacy of F protein vaccines with or without CpG oligodeoxynucleotide (CpG ODN) as an adjuvant in the upper and lower respiratory tracts in mice. F + CpG ODN induced higher levels of F-specific IgG than that induced by F alone; however, levels of neutralizing antibodies did not increase compared to those induced by F alone. F + CpG ODN induced T helper 1 (Th1) cells while F alone induced T helper 2 (Th2) cells. Moreover, F + CpG ODN improved the protection against RSV challenge in the upper respiratory tract compared to F alone, which was largely dependent on CD4 T cells. Meanwhile, both F + CpG ODN and F alone protected the lower respiratory tract. In conclusion, we demonstrated that induction of F-specific Th1 cells is an effective strategy to prevent RSV challenge in the upper respiratory tract in F protein vaccines. These data support the development of novel F protein vaccines.
呼吸道合胞病毒（RSV）是全球严重呼吸道疾病的主要病因，尤其是在婴儿和老年人中。针对融合糖蛋白（F 蛋白）的疫苗——RSV 的一种表面抗原——在预防 RSV 相关严重下呼吸道疾病方面非常有效。然而，这些疫苗对上呼吸道挑战的疗效需要提高。在这里，我们旨在研究 F 蛋白疫苗联合或不联合 CpG 寡脱氧核苷酸（CpG ODN）作为佐剂在上、下呼吸道中在小鼠体内的疗效。F+CpG ODN 诱导的 F 特异性 IgG 水平高于单独的 F 诱导的水平；然而，与单独的 F 诱导的水平相比，中和抗体的水平并没有增加。F+CpG ODN 诱导 T 辅助细胞 1（Th1）细胞，而单独的 F 诱导 T 辅助细胞 2（Th2）细胞。此外，与单独的 F 相比，F+CpG ODN 在上呼吸道中提高了对 RSV 挑战的保护作用，这在很大程度上依赖于 CD4 T 细胞。同时，F+CpG ODN 和 F 单独都保护下呼吸道。总之，我们证明了诱导 F 特异性 Th1 细胞是预防 F 蛋白疫苗上呼吸道 RSV 挑战的有效策略。这些数据支持新型 F 蛋白疫苗的开发。
