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评价多价重组弓形虫嵌合蛋白免疫后对 T. gondii 的长期免疫和保护作用。

Evaluation of long-term immunity and protection against T. gondii after immunization with multivalent recombinant chimeric T. gondii proteins.

机构信息

Department of Molecular Microbiology, Faculty of Biology and Environmental Protection, University of Lodz, Banacha 12/16, 90-237, Łódź, Poland.

Bio-Med-Chem Doctoral School of the University of Lodz and Lodz Institutes of the Polish Academy of Sciences, Faculty of Biology and Environmental Protection, University of Lodz, Banacha 12/16, 90-237, Łódź, Poland.

出版信息

Sci Rep. 2023 Aug 10;13(1):12976. doi: 10.1038/s41598-023-40147-z.

Abstract

Toxoplasmosis caused by the opportunistic, cosmopolitan protozoan Toxoplasma gondii is one of the most common parasitoses in the world. Although it may prove dangerous or even fatal for immunocompromised individuals, immunoprophylaxis for humans is still nonexistent. Thus, the aim of the current work was to assess the ability of two immunogenic recombinant chimeric T. gondii proteins, SAG2-GRA1-ROP1 (SGR) and SAG1-MIC1-MAG1-GRA2 (SMMG), selected in previous experiments to induce long-lasting immunity when administered with a safe adjuvant. Thus, the determination of immunological parameters and parasite challenge were performed both two weeks after the last boost injection and 6 months postvaccination. Both experimental vaccines triggered specific humoral and cellular responses in immunized C3H/HeOuJ male mice, characterized by the production of specific IgG (IgG1/IgG2a) antibodies in vivo and the synthesis of key Th1/Th2 cytokines by Toxoplasma lysate antigen-stimulated splenocytes in vitro. Although the levels of specific antibodies and cytokine release were in most cases lower six months postimmunization, the protection rates conferred by the vaccination were comparable regardless of the time after the administration of the last vaccine dose. The results indicate that both preparations induce long-lasting immunity, which makes them attractive candidates for further research aimed at boosting their immunogenicity and immunoprotective capacity.

摘要

弓形虫病是由机会主义的世界性原生动物弓形虫引起的,是世界上最常见的寄生虫病之一。尽管它可能对免疫功能低下的个体造成危险甚至致命,但人类仍然没有免疫预防措施。因此,目前的工作旨在评估两种免疫原性重组嵌合弓形虫蛋白 SAG2-GRA1-ROP1(SGR)和 SAG1-MIC1-MAG1-GRA2(SMMG)的能力,这些蛋白在前一次实验中被选择与安全佐剂一起使用,以诱导持久免疫力。因此,在最后一次加强注射后两周和接种疫苗后 6 个月,同时进行了免疫参数和寄生虫挑战的测定。两种实验疫苗均能在免疫 C3H/HeOuJ 雄性小鼠中引发特异性体液和细胞反应,其特征是体内产生特异性 IgG(IgG1/IgG2a)抗体,以及经弓形虫裂解物抗原刺激的脾细胞在体外合成关键 Th1/Th2 细胞因子。尽管在免疫后 6 个月,特异性抗体和细胞因子释放的水平在大多数情况下较低,但无论最后一次疫苗接种后时间如何,疫苗接种所赋予的保护率都是相当的。结果表明,这两种制剂均能诱导持久免疫力,这使它们成为进一步研究的有吸引力的候选者,旨在提高其免疫原性和免疫保护能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97e5/10415312/1ebede4b524b/41598_2023_40147_Fig1_HTML.jpg

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