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Transgenic Eimeria tenella as a vaccine vehicle: expressing TgSAG1 elicits protective immunity against Toxoplasma gondii infections in chickens and mice

机译:转基因艾美球虫为疫苗载体:表达TgSAG1引发对鸡和小鼠弓形虫感染的保护性免疫

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摘要

The surface antigen 1 of Toxoplasma gondii (TgSAG1) is a major immunodominant antigen and is widely considered an ideal candidate for the development of an effective recombinant vaccine against toxoplasmosis. Eimeria tenella, an affinis apicomplexan parasite with T. gondii, is a potential vaccine vector carrying exogenous antigens that stimulates specific immune responses. Here, we engineered TgSAG1 into E. tenella and obtained a stably transfected E. tenella line (Et-TgSAG1). We found TgSAG1 localized on the cell surface of Et-TgSAG1, which is similar to its native distribution in T. gondii tachyzoites. We immunized the chickens with Et-TgSAG1 orally and detected TgSAG1-specific immune responses, which partly reduced T. gondii infection. In the mouse model, we immunized the mice with Et-TgSAG1 sporozoites intraperitoneally and challenged them with T. gondii tachyzoites RH strain. We found that the mice immunized with Et-TgSAG1 showed a TgSAG1 specific Th 1-dominant immune response and a prolonged survival time compared with wild-type E. tenella and non-immunized mice. Collectively, our results demonstrated that Et-TgSAG1, utilized as a recombinant vaccine against toxoplasmosis, could be applied in both chickens and mice. Our findings also provide a promising persuasion for the development of transgenic Eimeria as vaccine vectors for use in birds and mammals.
机译:弓形虫的表面抗原1(TgSAG1)是主要的免疫优势抗原,被广泛认为是开发有效的抗弓形虫疫苗的理想候选者。艾美球虫是一种带有弓形虫的亲和性复合体寄生虫,是一种潜在的疫苗载体,带有刺激特定免疫反应的外源抗原。在这里,我们工程改造TgSAG1到大肠杆菌,并获得稳定转染的大肠杆菌(Et-TgSAG1)。我们发现TgSAG1定位在Et-TgSAG1的细胞表面,这与它在弓形虫速殖子中的天然分布相似。我们通过Et-TgSAG1口服免疫鸡,并检测到TgSAG1特异性免疫反应,从而部分减少了弓形虫的感染。在小鼠模型中,我们腹膜内用Et-TgSAG1子孢子免疫小鼠,并用弓形虫速殖子RH株攻击它们。我们发现,与野生型大肠杆菌和未免疫小鼠相比,用Et-TgSAG1免疫的小鼠表现出TgSAG1特异的Th 1优势免疫应答,并且存活时间延长。总体而言,我们的结果表明,用作抗弓形虫病的重组疫苗的Et-TgSAG1可以应用于鸡和小鼠。我们的发现还为开发转基因艾美球虫作为用于鸟类和哺乳动物的疫苗载体提供了有希望的说服力。

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