Rodriguez Leslie, Adam Awadalkareem, Luo Huanle, Osman Samantha R, Plante Kenneth, Rossi Shannan L, Weaver Scott C, Wang Tian
Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA.
Pathogens. 2025 Aug 30;14(9):863. doi: 10.3390/pathogens14090863.
Eilat (EILV)/chikungunya virus (CHIKV) is a chimeric virus that contains the nonstructural proteins and cis-acting sequences of EILV and the structural proteins of CHIKV. EILV/CHIKV vaccination is known to protect with a single dose against wild-type (WT) CHIKV challenge in mice and non-human primates. The underlying immune mechanism of the vaccine-induced host protection remains unknown. γδ T cells react to WT CHIKV infection by controlling the virus-induced tissue inflammation and damage. Here, we found that γδ T cells contribute to EILV/CHIKV-induced host protection against WT CHIKV infection. TCRδ mice, which are deficient of γδ T cells, had impaired CHIKV-specific CD8 T cell responses, antibody production and memory B cell responses following vaccination. Both antibody and CD8 T cells of EILV/CHIKV-vaccinated mice were required for protection type I interferon receptor deficient mice from lethal WT CHIKV infection. Moreover, γδ T cells expanded quickly in response to EILV/CHIKV vaccination. TCRδ mice, had lower levels of innate immune cytokines and impaired activation of antigen presenting cell (APCs). Overall, γδ T cells contribute to EILV/CHIKV-induced host protection by promoting APC maturation, T cell priming and the induction of humoral immune responses upon EILV/CHIKV vaccination.
埃拉特病毒（EILV）/基孔肯雅病毒（CHIKV）是一种嵌合病毒，它包含埃拉特病毒的非结构蛋白和顺式作用序列以及基孔肯雅病毒的结构蛋白。已知埃拉特病毒/基孔肯雅病毒疫苗接种单剂量就能保护小鼠和非人灵长类动物免受野生型（WT）基孔肯雅病毒攻击。疫苗诱导宿主产生保护作用的潜在免疫机制尚不清楚。γδT细胞通过控制病毒诱导的组织炎症和损伤来应对野生型基孔肯雅病毒感染。在此，我们发现γδT细胞有助于埃拉特病毒/基孔肯雅病毒诱导宿主抵御野生型基孔肯雅病毒感染。缺乏γδT细胞的TCRδ小鼠在接种疫苗后，其基孔肯雅病毒特异性CD8 T细胞反应、抗体产生和记忆B细胞反应均受损。埃拉特病毒/基孔肯雅病毒疫苗接种小鼠的抗体和CD8 T细胞对于保护I型干扰素受体缺陷小鼠免受致死性野生型基孔肯雅病毒感染都是必需的。此外，γδT细胞对埃拉特病毒/基孔肯雅病毒疫苗接种反应迅速扩增。TCRδ小鼠的固有免疫细胞因子水平较低，抗原呈递细胞（APC）的激活受损。总体而言，γδT细胞通过促进抗原呈递细胞成熟、T细胞启动以及在埃拉特病毒/基孔肯雅病毒疫苗接种时诱导体液免疫反应，来促成埃拉特病毒/基孔肯雅病毒诱导的宿主保护作用。
