Department of Immunoparasitology, University of Lodz, Lodz, Poland.
Exp Parasitol. 2012 May;131(1):133-8. doi: 10.1016/j.exppara.2012.02.026. Epub 2012 Mar 14.
Toxoplasmosis is one of the world's most widespread zoonoses caused by protozoan parasite Toxoplasma gondii. The development of an effective vaccine for controlling toxoplasmosis is an extremely important issue due to the serious clinical and veterinary outcomes of this parasitosis. The objective of this study was evaluation of vaccine potential of three trivalent subunit recombinant vaccines composed of rROP2+rGRA4+rSAG1, rROP2+rROP4+rGRA4 and rROP2+rROP4+rSAG1 against chronic toxoplasmosis in BALB/c (H-2(d)) mice. All tested vaccines provided a partial protection against challenge with tissue cysts of the low virulence DX T. gondii strain, but the strongest level of protection was induced by the mixtures of both rhoptry proteins (rROP2 and rROP4) administered with the dense granule rGRA4 antigen or the main surface rSAG1 protein. The average parasite burden in these groups of vaccinated BALB/c mice was reduced by 84% and 77%, respectively, compared to the control PBS-injected animals. The vaccine-induced protection was correlated with the development of cellular and humoral immune responses demonstrated by the antigen-specific in vitro proliferation of spleen cells, the specific antigen-induced in vitro synthesis of Th1-type cytokines, IFN-γ and IL-2, and the generation of the high titers of systemic antigen-specific IgG1 and IgG2a antibodies. This study completed and confirmed our earlier investigations in C3H/HeJ (H-2(k)) and C57BL/6 (H-2(b)) mouse strains on the utility of the tested trivalent recombinant antigen-cocktails as potential vaccines against chronic toxoplasmosis and showed that particularly rROP2+rROP4+rGRA4 and rROP2+rROP4+rSAG1 protein-combinations are very effective in the development of a high level of protection irrespective of the genetic backgrounds and innate resistance to toxoplasmosis of the laboratory mice. It makes these two mixtures of recombinant antigens very promising for further experiments.
弓形虫病是由原生动物寄生虫弓形虫引起的世界上最广泛的人畜共患病之一。由于这种寄生虫病的严重临床和兽医后果，开发一种有效的疫苗来控制弓形虫病是一个极其重要的问题。本研究的目的是评估由 rROP2+rGRA4+rSAG1、rROP2+rROP4+rGRA4 和 rROP2+rROP4+rSAG1 三种三价亚单位重组疫苗对 BALB/c（H-2(d)) 小鼠慢性弓形虫病的疫苗潜力。所有测试的疫苗都对低毒力 DX T. gondii 株组织包囊的攻击提供了部分保护，但用 rhoptry 蛋白（rROP2 和 rROP4）与致密颗粒 rGRA4 抗原或主要表面 rSAG1 蛋白联合给药的混合物诱导了最强水平的保护。与对照 PBS 注射动物相比，这些接种 BALB/c 小鼠的寄生虫负荷平均减少了 84%和 77%。疫苗诱导的保护与细胞和体液免疫反应的发展相关，这表现为脾细胞的抗原特异性体外增殖、Th1 型细胞因子 IFN-γ 和 IL-2 的特异性抗原诱导的体外合成以及系统抗原特异性 IgG1 和 IgG2a 抗体的高滴度产生。这项研究完成并证实了我们之前在 C3H/HeJ（H-2(k)) 和 C57BL/6（H-2(b)) 小鼠品系中进行的研究，证明了测试的三价重组抗原混合物作为针对慢性弓形虫病的潜在疫苗的效用，并表明特别是 rROP2+rROP4+rGRA4 和 rROP2+rROP4+rSAG1 蛋白混合物在发展高水平保护方面非常有效，而与实验室小鼠的遗传背景和对弓形虫病的固有抵抗力无关。这使得这两种重组抗原混合物非常有前途，可以进行进一步的实验。
