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

Transgenic Eimeria tenella as a vaccine vehicle: expressing TgSAG1 elicits protective immunity against Toxoplasma gondii infections in chickens and mice.
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转基因柔嫩艾美耳球虫作为疫苗载体:表达 TgSAG1 可在鸡和小鼠中引发针对弓形虫感染的保护性免疫力

DOI:
10.1038/srep29379
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发表时间:
2016-07-08
期刊:
影响因子:
4.6
通讯作者:
Suo X
Suo X
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Tang X;Yin G;Qin M;Tao G;Suo J;Liu X;Suo X

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弓形虫表面抗原 1 (TgSAG1) 是一种主要的免疫显性抗原,被广泛认为是开发有效的弓形体病重组疫苗的理想候选抗原。柔嫩艾美耳球虫(Eimeria tenella)是一种弓形虫的亲和寄生虫,是一种潜在的疫苗载体,携带可刺激特异性免疫反应的外源抗原。在这里,我们将 TgSAG1 工程化到柔嫩 E. tenella 中,并获得了稳定转染的 E. tenella 品系 (Et-TgSAG1)。我们发现TgSAG1定位于Et-TgSAG1的细胞表面,这与其在弓形虫速殖子中的天然分布相似。我们用 Et-TgSAG1 口服免疫鸡,并检测到 TgSAG1 特异性免疫反应,这在一定程度上减少了弓形虫感染。在小鼠模型中,我们用 Et-TgSAG1 子孢子腹腔注射免疫小鼠,并用弓形虫速殖子 RH 菌株攻击它们。我们发现,与野生型柔嫩球虫和未免疫小鼠相比,用 Et-TgSAG1 免疫的小鼠表现出 TgSAG1 特异性 Th 1 主导的免疫反应,并且存活时间更长。总的来说,我们的结果表明,Et-TgSAG1 作为弓形体病重组疫苗,可以应用于鸡和小鼠。我们的研究结果还为开发转基因艾美耳球虫作为鸟类和哺乳动物的疫苗载体提供了有希望的说服力。
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.