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弓形虫:含基因佐剂B7-2的ROP16/GRA7多组分DNA疫苗诱导的免疫反应和保护效力

Toxoplasma gondii: immune response and protective efficacy induced by ROP16/GRA7 multicomponent DNA vaccine with a genetic adjuvant B7-2.

作者信息

Liu Qi, Wang Fuwu, Wang Guan, Zhao Qunli, Min Juan, Wang Shuai, Cong Hua, Li Ying, He Shenyi, Zhou Huaiyu

机构信息

Department of Parasitology; Shandong University School of Medicine; Jinan, Shandong PR China.

Department of Histology and Embryology; Shandong University School of Medicine; Jinan, Shandong PR China.

出版信息

Hum Vaccin Immunother. 2014;10(1):184-91. doi: 10.4161/hv.26703. Epub 2013 Oct 7.

Abstract

Toxoplasma gondii infection occurs commonly in humans and other warm-blooded animals. Its serious impact on public health and livestock sectors makes the development of an effective vaccine particularly important. In the current study, we constructed a multiantigenic DNA vaccine expressing ROP16 and GRA7 of T. gondii and evaluated the protective efficacy of these two fragments with or without a plasmid encoding murine costimulatory molecule B7-2. These recombinant eukaryotic expression plasmids were termed pROP16, pGRA7, pROP16-GRA7 and pB7-2, respectively. After intramuscular immunization in Kunming mice, we assessed the immune response using cytokine and antibody determinations, T lymphocyte subsets analysis, and the survival times of mice post acute T. gondii challenge. The results showed that mice immunized with the multiantigenic DNA vaccine pROP16-GRA7 gained higher levels of IgG titers and IgG2a subclass titers, production of IFN-γ, percentage of CD8+ T cells and median survival times against the acute infection of T. gondii compared with those of mice administered with pROP16 or pGRA7 and those in control groups. Moreover, the adjuvant pB7-2 formulated with DNA vaccine boosted these humoral and cellular (Th1, CD8+ T cell) immune responses. Therefore, it might be a promising genetic adjuvant to DNA vaccine against T. gondii for further investigation.

摘要

弓形虫感染在人类和其他温血动物中普遍存在。其对公共卫生和畜牧业的严重影响使得开发有效的疫苗尤为重要。在本研究中,我们构建了一种表达弓形虫ROP16和GRA7的多抗原DNA疫苗,并评估了这两个片段在有或没有编码小鼠共刺激分子B7-2的质粒情况下的保护效果。这些重组真核表达质粒分别命名为pROP16、pGRA7、pROP16-GRA7和pB7-2。在昆明小鼠中进行肌肉注射免疫后,我们通过细胞因子和抗体检测、T淋巴细胞亚群分析以及急性弓形虫攻击后小鼠的存活时间来评估免疫反应。结果表明,与接种pROP16或pGRA7的小鼠以及对照组相比,用多抗原DNA疫苗pROP16-GRA7免疫的小鼠针对弓形虫急性感染获得了更高水平的IgG滴度和IgG2a亚类滴度、IFN-γ的产生、CD8 + T细胞百分比和中位存活时间。此外,与DNA疫苗配制的佐剂pB7-2增强了这些体液和细胞(Th1,CD8 + T细胞)免疫反应。因此,它可能是一种有前途的针对弓形虫DNA疫苗的遗传佐剂,有待进一步研究。

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