Department of Immunoparasitology, University of Lodz, Lodz, Poland.
Vaccine. 2011 Jan 17;29(4):821-30. doi: 10.1016/j.vaccine.2010.11.002. Epub 2010 Nov 16.
The great clinical and economical impact of Toxoplasma gondii infections makes the development of an effective vaccine for controlling toxoplasmosis an extremely important aim. In the presented study, we evaluate the protective and immunogenic properties of three recombinant subunit vaccines composed of rROP2+rGRA4+rSAG1, rROP2+rROP4+rGRA4 and rROP2+rROP4+rSAG1 proteins of T. gondii in an experimental toxoplasmosis model in the C3H/HeJ and C57BL/6 mouse strains. All three recombinant vaccines induced partial protection as measured by the reduction of brain cyst burden following challenge with five tissue cysts of the low virulence DX T. gondii strain. The level of protection was dependent on the antigen composition of the vaccine and the genetic background of the laboratory animals. The strongest protection against chronic toxoplasmosis was induced in both C3H/HeJ and C57BL/6 mice by the mixture of rhoptry proteins rROP2 and rROP4 combined with tachyzoite major protein rSAG1. The average parasite burden in these groups of mice was reduced by 71% and 90%, respectively, compared to non-vaccinated mice. The observed protective effect was related to the vaccine-induced cellular and humoral immune responses, as measured by the antigen-induced release of the Th1 cytokines IFN-γ and IL-2, the antigen-stimulated proliferation of spleen cells of vaccinated animals in comparison to control animals and the development of systemic antigen-specific IgG1 and IgG2a (C3H/HeJ) or IgG2c (C57BL/6) antibodies. Our studies show that recombinant rROP2, rROP4, rGRA4 and rSAG1 antigens may be promising candidates for a subunit vaccine against toxoplasmosis. Additionally, we demonstrate that the ideal composition of vaccine antigens can be equally effective in mice with different genetic backgrounds and variable levels of innate resistance to toxoplasmosis, resulting in strong protection against T. gondii invasion.
弓形虫感染具有重大的临床和经济影响，因此开发一种有效的疫苗来控制弓形体病是一个极其重要的目标。在本研究中，我们评估了三种由 rROP2+rGRA4+rSAG1、rROP2+rROP4+rGRA4 和 rROP2+rROP4+rSAG1 蛋白组成的重组亚单位疫苗在 C3H/HeJ 和 C57BL/6 两种小鼠品系的实验性弓形体病模型中的保护和免疫原性。所有三种重组疫苗都能部分保护动物，具体表现为用低毒力 DX 弓形虫株的五个组织包囊攻击后，脑部囊泡负荷减少。保护水平取决于疫苗的抗原组成和实验动物的遗传背景。在 C3H/HeJ 和 C57BL/6 两种小鼠中，rhoptry 蛋白 rROP2 和 rROP4 与速殖子主要蛋白 rSAG1 的混合物能诱导最强的抗慢性弓形体病作用。与未接种疫苗的小鼠相比，这两组小鼠的寄生虫负荷分别降低了 71%和 90%。观察到的保护作用与疫苗诱导的细胞和体液免疫反应有关，如 Th1 细胞因子 IFN-γ 和 IL-2 的抗原诱导释放、疫苗接种动物的脾细胞与对照动物相比的抗原刺激增殖以及系统抗原特异性 IgG1 和 IgG2a（C3H/HeJ）或 IgG2c（C57BL/6）抗体的产生。我们的研究表明，重组 rROP2、rROP4、rGRA4 和 rSAG1 抗原可能是弓形虫病亚单位疫苗的有前途的候选物。此外，我们证明了疫苗抗原的理想组成在具有不同遗传背景和对弓形体病固有抵抗力不同的小鼠中同样有效，从而能对 T. gondii 入侵产生强大的保护作用。
