Toxoplasma gondii: The vaccine potential of three trivalent antigen-cocktails composed of recombinant ROP2, ROP4, GRA4 and SAG1 proteins against chronic toxoplasmosis in BALB/c mice
Toxoplasma gondii: The vaccine potential of three trivalent antigen-cocktails composed of recombinant ROP2, ROP4, GRA4 and SAG1 proteins against chronic toxoplasmosis in BALB/c mice
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DOI：
10.1016/j.exppara.2012.02.026
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发表时间：
2012-05-01
影响因子：
2.1
通讯作者：
Dlugonska, Henryka
中科院分区：
文献类型：
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作者：
Dziadek, Bozena;Gatkowska, Justyna;Dlugonska, Henryka
弓形虫病是由弓形虫原虫引起的世界上最广泛的人畜共患病之一。由于弓形虫病的严重临床和兽医后果，开发有效的疫苗来控制弓形虫病是一个极其重要的问题。本研究的目的是评价由rROP2 + rGRA4 + rSAG1、rROP2 + rROP4 + rGRA4和rROP2 + rROP4 + rSAG1组成的三价重组疫苗对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弓形虫菌株组织囊肿的攻击提供部分保护，但最强的保护水平是由两种组织蛋白（rROP2和rROP4）与致密颗粒rGRA4抗原或主要表面rSAG1蛋白混合施用。与注射pbs的对照动物相比，这些接种BALB/c疫苗的小鼠的平均寄生虫负担分别减少了84%和77%。疫苗诱导的保护作用与脾细胞抗原特异性体外增殖、特异性抗原诱导的tm型细胞因子、ifn - γ和IL-2的体外合成以及高滴度的全身抗原特异性IgG1和IgG2a抗体的产生相关。本研究完成并证实了我们早期在C3H/Hej （H-2(k)）和C57BL/6 （H-2(b)）小鼠品系中对三价重组抗原鸡尾酒作为慢性弓形虫病潜在疫苗的研究，并表明特别是rROP2 + rROP4 + rGRA4和rROP2 + rROP4 + rSAG1蛋白组合在开发高水平保护方面非常有效，而不考虑遗传背景和实验室对弓形虫病的先天抗性老鼠。这使得这两种重组抗原的混合物在进一步的实验中非常有希望。(C) 2012爱思唯尔公司版权所有。
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 TM-type cytokines, IFN-gamma 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. (C) 2012 Elsevier Inc. All rights reserved.