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编码GRA8的DNA疫苗诱导的保护性免疫反应对小鼠模型急性弓形虫病的评估

Evaluation of Protective Immune Response Induced by a DNA Vaccine Encoding GRA8 against Acute Toxoplasmosis in a Murine Model.

作者信息

Chu Jia-Qi, Huang Shuai, Ye Wei, Fan Xuan-Yan, Huang Rui, Ye Shi-Cai, Yu Cai-Yuan, Wu Wei-Yun, Zhou Yu, Zhou Wei, Lee Young-Ha, Quan Juan-Hua

机构信息

Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, China.

Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, China.

出版信息

Korean J Parasitol. 2018 Aug;56(4):325-334. doi: 10.3347/kjp.2018.56.4.325. Epub 2018 Aug 31.

Abstract

Toxoplasma gondii is an apicomplexan zoonotic protozoan parasite that infects most species of warm-blooded animals, including humans. The heavy incidence and severe or lethal damage caused by T. gondii infection clearly indicate a need for the development of an effective vaccine. T. gondii GRA8 is a member of the dense granules protein family and is used as a marker of acute infection. In the present study, we evaluated the protective immunity induced by DNA vaccination based on a recombinant eukaryotic plasmid, pDsRed2-GRA8, against acute toxoplasmosis in mice. BALB/c mice were intramuscularly immunized with the pDsRed2-GRA8 plasmid and then challenged by infection with the highly virulent GFP-RH strain of T. gondii. The specific immune responses and protective efficacy against T. gondii of this vaccine were analyzed by measuring cytokine and serum antibody titers, splenocyte proliferation assays, and the survival times of mice after challenge. Our results showed that mice immunized with pDsRed2-GRA8 demonstrated specific humoral and cellular responses, induced higher IgG antibody titers with predominant IgG2a production; increased levels of IL-10, IL-12 (p70), IFN-γ, TNF-α, and splenocyte proliferation; and prolonged survival times compared to those of control mice. The present study showed that DNA immunization with pDsRed2-GRA8 induced humoral and cellular immune responses, and all immunized mice showed greater Th1-type immune responses and longer survival times than those of control mice. These results indicated that T. gondii GRA8 DNA immunization induces a partial protective effect against acute toxoplasmosis.

摘要

刚地弓形虫是一种顶复门动物源性原生动物寄生虫,可感染包括人类在内的大多数温血动物物种。刚地弓形虫感染导致的高发病率以及严重或致命损害清楚地表明需要开发一种有效的疫苗。刚地弓形虫致密颗粒蛋白8(GRA8)是致密颗粒蛋白家族的成员,用作急性感染的标志物。在本研究中,我们评估了基于重组真核质粒pDsRed2-GRA8的DNA疫苗对小鼠急性弓形虫病诱导的保护性免疫。将BALB/c小鼠肌肉注射pDsRed2-GRA8质粒,然后用刚地弓形虫的高毒力绿色荧光蛋白(GFP)-RH株进行感染攻击。通过测量细胞因子和血清抗体滴度、脾细胞增殖试验以及攻击后小鼠的存活时间,分析了该疫苗对刚地弓形虫的特异性免疫反应和保护效果。我们的结果表明,用pDsRed2-GRA8免疫的小鼠表现出特异性体液和细胞反应,诱导产生更高的IgG抗体滴度,且主要产生IgG2a;白细胞介素-10(IL-10)、白细胞介素-12(p70)、干扰素-γ(IFN-γ)、肿瘤坏死因子-α(TNF-α)水平升高以及脾细胞增殖;与对照小鼠相比,存活时间延长。本研究表明,用pDsRed2-GRA8进行DNA免疫可诱导体液和细胞免疫反应,所有免疫小鼠均表现出比对照小鼠更强的Th1型免疫反应和更长的存活时间。这些结果表明,刚地弓形虫GRA8 DNA免疫对急性弓形虫病诱导了部分保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9de2/6137303/445bf2b416b5/kjp-56-4-325f1.jpg

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