Cao Aiping, Liu Yuan, Wang Jingjing, Li Xun, Wang Shuai, Zhao Qunli, Cong Hua, He Shenyi, Zhou Huaiyu
Department of Parasitology, School of Medicine, Shandong University, PR China.
Department of Pharmaceutical Science, School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, PR China.
Vaccine. 2015 Nov 27;33(48):6757-62. doi: 10.1016/j.vaccine.2015.10.077. Epub 2015 Oct 27.
Toxoplasma gondii (T. gondii) is an obligate, intracellular, protozoan parasite that infects large variety of warm-blooded animals including humans, livestock, and marine mammals, and causes the disease toxoplasmosis. Although T. gondii infection rates differ significantly from country to country, it still has a high morbidity and mortality. In these circumstances, developing an effective vaccine against T. gondii is urgently needed for preventing and treating toxoplasmosis. The aim of this study was to construct a multi-epitopes DNA vaccine and evaluate the immune protective efficacy against acute toxoplasmosis in mice. Therefore, twelve T- and B-cell epitopes from SAG1, GRA2, GRA7 and ROP16 of T. gondii were predicted by bioinformatics analysis, and then a multi-epitopes DNA vaccine was constructed. Mice immunized with the multi-epitopes DNA vaccine gained higher levels of IgG titers and IgG2a subclass titers, significant production of gamma interferon (IFN-γ), percentage of T lymphocyte subsets, and longer survival times against the acute infection of T. gondii compared with those of mice administered with empty plasmid and those in control groups. Furthermore, a genetic adjuvant pEGFP-RANTES (pRANTES) could enhance the efficacy of the multi-epitopes DNA vaccine associating with humoral and cellular (Th1, CD8(+) T cell) immune responses. Above all, the DNA vaccine and the genetic adjuvant revealed in this study might be new candidates for further vaccine development against T. gondii infection.
刚地弓形虫是一种专性细胞内原生动物寄生虫,可感染包括人类、家畜和海洋哺乳动物在内的多种温血动物,并引发弓形虫病。尽管刚地弓形虫的感染率在不同国家之间存在显著差异,但其发病率和死亡率仍然很高。在这种情况下,迫切需要开发一种有效的抗刚地弓形虫疫苗来预防和治疗弓形虫病。本研究的目的是构建一种多表位DNA疫苗,并评估其对小鼠急性弓形虫病的免疫保护效果。因此,通过生物信息学分析预测了来自刚地弓形虫SAG1、GRA2、GRA7和ROP16的12个T细胞和B细胞表位,然后构建了一种多表位DNA疫苗。与接种空质粒的小鼠和对照组相比,用多表位DNA疫苗免疫的小鼠获得了更高水平的IgG滴度和IgG2a亚类滴度,显著产生了γ干扰素(IFN-γ),T淋巴细胞亚群百分比更高,并且在抵抗刚地弓形虫急性感染时存活时间更长。此外,一种基因佐剂pEGFP-RANTES(pRANTES)可以增强多表位DNA疫苗与体液免疫和细胞免疫(Th1、CD8(+) T细胞)反应相关的效果。最重要的是,本研究中揭示的DNA疫苗和基因佐剂可能是进一步开发抗刚地弓形虫感染疫苗的新候选物。