Yin Liang, Chai Dafei, Yue Yan, Dong Chunsheng, Xiong Sidong
Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow UniversitySuzhou, China.
Front Cell Infect Microbiol. 2017 Jun 8;7:247. doi: 10.3389/fcimb.2017.00247. eCollection 2017.
The recurrent Coxsackievirus B3 (CVB3) infection is the most important cause of intractable myocarditis which often leads to chronic myocarditis and even dilated cardiomyopathy. Therefore, enhanced DNA vaccines capable of memory CD8 T cells are essential for long-lasting immunological protection against CVB3 infection. In this study, absent in melanoma 2 (AIM2) was used as an adjuvant to enhance the induction of memory CD8 T cells elicited by VP1 (viral capsid protein 1) vaccine. Mice were intramuscularly injected with 50 μg AIM2 plasmid and equal amount of VP1 plasmid (pAIM2/pVP1) vaccine 4 times at 2 week-intervals. We observed that the protection of pAIM2/pVP1 vaccine against CVB3 challenge was evidenced by significantly improved cardiac function, reduced myocardial injuries, and increased survival rate when compared with immunization with pVP1. Co-immunization with pAIM2/pVP1 robustly augmented T lymphocytes proliferation and CVB3-specific cytotoxic T lymphocyte responses. Importantly, 16 weeks after the last immunization, pAIM2/pVP1 co-immunization significantly enhanced the expression of Bcl-6, SOCS3, and Sca-1 which are critical for memory CD8 T cells as compared with pVP1 immunization. Notably, CD8 T cells that are likely vaccine-induced memory T cells were responsible for the protective efficacy of pAIM2/pVP1 vaccine by abolition of a CD8 T cell immune response following a lethal dose of CVB3 infection. Our results indicate that AIM2-adjuvanted vaccine could be a potential and promising approach to promote a long-lasting protection against CVB3-induced myocarditis.
柯萨奇病毒B3（CVB3）反复感染是难治性心肌炎的最重要原因，常导致慢性心肌炎甚至扩张型心肌病。因此，能够增强记忆性CD8 T细胞的DNA疫苗对于持久免疫保护以抵御CVB3感染至关重要。在本研究中，黑色素瘤缺失因子2（AIM2）被用作佐剂，以增强由VP1（病毒衣壳蛋白1）疫苗引发的记忆性CD8 T细胞的诱导。小鼠每隔2周肌肉注射50μg AIM2质粒和等量的VP1质粒（pAIM2/pVP1）疫苗，共注射4次。我们观察到，与pVP1免疫相比，pAIM2/pVP1疫苗对CVB3攻击的保护作用表现为心脏功能显著改善、心肌损伤减轻和存活率提高。pAIM2/pVP1共免疫显著增强了T淋巴细胞增殖和CVB3特异性细胞毒性T淋巴细胞反应。重要的是，在最后一次免疫16周后，与pVP1免疫相比，pAIM2/pVP1共免疫显著增强了对记忆性CD8 T细胞至关重要的Bcl-6、SOCS3和Sca-1的表达。值得注意的是，可能是疫苗诱导的记忆T细胞的CD8 T细胞通过消除致死剂量CVB3感染后的CD8 T细胞免疫反应，对pAIM2/pVP1疫苗的保护效力起作用。我们的结果表明，AIM2佐剂疫苗可能是一种潜在且有前景的方法，可促进对CVB3诱导的心肌炎的持久保护。
