Department of Biotechnology.
BK21 FOUR Department of Biotechnology, The Catholic University of Korea, Bucheon.
J Infect Dis. 2024 May 15;229(5):1408-1418. doi: 10.1093/infdis/jiad392.
Developing new adjuvants that can effectively induce humoral and cellular immune responses while broadening the immune response is of great value. In this study, we aimed to develop single-stranded RNA adjuvants expressing (1) granulocyte monocyte colony-stimulating factor or (2) interleukin 18 based on the encephalomyocarditis virus internal ribosome entry site; we also tested their efficacy in combination with ovalbumin or inactivated influenza vaccines. Notably, cytokine-expressing RNA adjuvants increased the expression of antigen-presenting cell activation markers in mice. Specifically, when combined with ovalbumin, RNA adjuvants expressing granulocyte monocyte colony-stimulating factor increased CD4+ T-cell responses, while those expressing interleukin 18 increased CD8+ T-cell responses. Cytokine-expressing RNA adjuvants further increased the frequency of polyclonal T cells with the influenza vaccine and reduced the clinical illness scores and weight loss of mice after viral challenge. Collectively, our results suggest that cytokine-expressing RNA adjuvants can be applied to protein-based or inactivated vaccines to increase their efficacy.
开发能够有效诱导体液和细胞免疫反应同时拓宽免疫反应的新型佐剂具有重要意义。在本研究中，我们旨在基于脑心肌炎病毒内部核糖体进入位点开发表达（1）粒细胞-单核细胞集落刺激因子或（2）白细胞介素 18 的单链 RNA 佐剂；我们还测试了它们与卵清蛋白或灭活流感疫苗联合使用的效果。值得注意的是，细胞因子表达 RNA 佐剂增加了小鼠抗原呈递细胞激活标志物的表达。具体来说，当与卵清蛋白联合使用时，表达粒细胞-单核细胞集落刺激因子的 RNA 佐剂增加了 CD4+T 细胞反应，而表达白细胞介素 18 的 RNA 佐剂增加了 CD8+T 细胞反应。细胞因子表达 RNA 佐剂进一步增加了流感疫苗多克隆 T 细胞的频率，并降低了病毒攻击后小鼠的临床疾病评分和体重减轻。总之，我们的结果表明，细胞因子表达 RNA 佐剂可应用于基于蛋白质或灭活的疫苗以提高其功效。
