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作为遗传佐剂的GITRL增强肠道病毒71型VP1 DNA疫苗的免疫原性。

GITRL as a genetic adjuvant enhances enterovirus 71 VP1 DNA vaccine immunogenicity.

作者信息

Yuan Jing, Tang Xinyi, Yin Kai, Tian Jie, Rui Ke, Ma Jie, Mao Chaoming, Chen Jianguo, Lu Liwei, Xu Huaxi, Wang Shengjun

机构信息

Department of Laboratory Medicine, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, 212002, Jiangsu Province, China.

出版信息

Immunol Res. 2015 May;62(1):81-8. doi: 10.1007/s12026-015-8637-1.

Abstract

VP1 protein is the immunodominant capsid protein of enterovirus 71 (EV71) which is responsible for large outbreaks of hand, foot and mouth disease. It has been reported that glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) and its ligand (GITRL) are involved in modulating both innate and adaptive immune responses. In this study, a DNA vaccine vector encoding EV71 VP1 gene and mGITRL gene (pIRES/VP1/mGITRL) was constructed. And female Balb/c mice were immunized intramuscularly with the DNA vaccine. Compared with the groups immunized with pIRES, pIRES/VP1, pIRES/mGITRL and PBS, the inoculation of pIRES/VP1/mGITRL induced a higher levels of EV71 VP1-specific antibody and specific antibody-forming cells. However, significantly higher levels of CD4(+)Th1, Th2 and CD8(+)IFN-γ(+)T cells were found in the pIRES/VP1/mGITRL group compared with control groups. Our results demonstrate that a novel DNA vaccine, expressing VP1 and mGITRL, could effectively elicit both humoral and cell-mediated immune responses against EV71 VP1 in mice. Thus, the mGITRL may be used as molecular adjuvant for EV71 DNA vaccine.

摘要

VP1蛋白是肠道病毒71型(EV71)的免疫显性衣壳蛋白,该病毒是手足口病大规模暴发的病原体。据报道,糖皮质激素诱导的肿瘤坏死因子受体相关蛋白(GITR)及其配体(GITRL)参与调节先天性和适应性免疫反应。在本研究中,构建了一种编码EV71 VP1基因和小鼠GITRL基因的DNA疫苗载体(pIRES/VP1/mGITRL)。用该DNA疫苗对雌性Balb/c小鼠进行肌肉注射免疫。与用pIRES、pIRES/VP1、pIRES/mGITRL和PBS免疫的组相比,接种pIRES/VP1/mGITRL诱导产生了更高水平的EV71 VP1特异性抗体和特异性抗体形成细胞。然而,与对照组相比,在pIRES/VP1/mGITRL组中发现CD4(+)Th1、Th2和CD8(+)IFN-γ(+)T细胞水平显著更高。我们的结果表明,一种表达VP1和mGITRL的新型DNA疫苗能够有效地在小鼠体内引发针对EV71 VP1的体液免疫和细胞介导的免疫反应。因此,mGITRL可用作EV71 DNA疫苗的分子佐剂。

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