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用编码 B 细胞和 T 细胞多表位 SAG1、ROP16、MIC4、GRA12、M2AP 和多表位 ROP8 的 DNA 疫苗诱导 BALB/c 小鼠对急性和慢性弓形虫病的保护性免疫。

Protective immunity induced with a DNA vaccine encoding B- and T-cells multi-epitope SAG1, ROP16, MIC4, GRA12, M2AP, and multi-epitope ROP8 against acute and chronic toxoplasmosis in BALB/c mice.

机构信息

Department of Parasitology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

出版信息

Exp Parasitol. 2022 Nov;242:108385. doi: 10.1016/j.exppara.2022.108385. Epub 2022 Sep 24.

Abstract

BACKGROUND

T. gondii infection is characterized by a high global prevalence. Nearly, 16-40% of people have been infected by T. gondii. Although T. gondii often causes subclinical infection, it may cause severe complications in newborns with congenital infection and immunocompromised individuals. Constant attempts of scientists have made valuable findings in the development of T. gondii candidate vaccines. However, an effective vaccine has not been successfully developed yet. In this study, multi-epitope SAG1, MIC4, ROP16, M2AP, GRA12, and multi-epitope ROP8 were injected into BALB/c mice intramuscularly, as cocktailed plasmids or as single-gene plasmids to assess the immune response against chronic and acute Toxoplasma infection.

METHODS

BALB/c mice were immunized on days 0, 21, and 42. The immune responses of both vaccinated and control groups were evaluated using cytokine and antibody measurements, lymphocyte proliferation assay, survival time, and average number of cysts in each brain.

RESULTS

The results indicated that DNA vaccination using multi-epitope ROP8 and multi-epitope SAG1, ROP16, MIC4, GRA12, M2AP could elicit both cellular and humoral immune responses, and enhanced the survival time in BALB/c mice. Also, the administration of multi-epitope ROP8 plus multi-epitope SAG1, ROP16, MIC4, GRA12, M2AP could enhance the concentrations of IgG antibody, elicit a mixed IgG1/IgG2a reaction with the predominance of the IgG2a, increase the release of IFN-γ cytokine, prolonge the survival time, and reduce the brain cysts.

CONCLUSIONS

Here, we report that vaccination using cocktailed plasmids could induce better protective immunity compared to single plasmid for acute and chronic T. gondii infection.

摘要

背景

刚地弓形虫感染具有很高的全球流行率。近 16-40%的人感染了刚地弓形虫。虽然刚地弓形虫通常引起亚临床感染,但在先天性感染的新生儿和免疫功能低下的个体中,它可能引起严重的并发症。科学家们不断努力,在刚地弓形虫候选疫苗的开发方面取得了有价值的发现。然而,一种有效的疫苗尚未成功开发。在这项研究中,多表位 SAG1、MIC4、ROP16、M2AP、GRA12 和多表位 ROP8 被肌肉内注射到 BALB/c 小鼠中,作为鸡尾酒质粒或单基因质粒,以评估针对慢性和急性弓形虫感染的免疫反应。

方法

BALB/c 小鼠在第 0、21 和 42 天进行免疫。通过细胞因子和抗体测量、淋巴细胞增殖试验、存活时间和每个大脑中的平均囊数评估接种组和对照组的免疫反应。

结果

结果表明,使用多表位 ROP8 和多表位 SAG1、ROP16、MIC4、GRA12、M2AP 的 DNA 疫苗接种可以引发细胞和体液免疫反应,并延长 BALB/c 小鼠的存活时间。此外,多表位 ROP8 加多表位 SAG1、ROP16、MIC4、GRA12、M2AP 的给药可以提高 IgG 抗体的浓度,引起 IgG1/IgG2a 的混合反应,以 IgG2a 为主,增加 IFN-γ 细胞因子的释放,延长存活时间,并减少大脑中的囊。

结论

在这里,我们报告说,与急性和慢性刚地弓形虫感染的单质粒相比,鸡尾酒质粒的疫苗接种可以诱导更好的保护性免疫。

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