Identification and characterization of Toxoplasma gondii aspartic protease 1 as a novel vaccine candidate against toxoplasmosis.

Identification and characterization of Toxoplasma gondii aspartic protease 1 as a novel vaccine candidate against toxoplasmosis.
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弓形虫天冬氨酸蛋白酶 1 作为弓形虫病新型候选疫苗的鉴定和表征

DOI:
10.1186/1756-3305-6-175
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发表时间:
2013-06-14
影响因子:
3.2
通讯作者:
He S
He S
中科院分区:
医学2区
文献类型:
--
作者:
Zhao G;Zhou A;Lu G;Meng M;Sun M;Bai Y;Han Y;Wang L;Zhou H;Cong H;Zhao Q;Zhu XQ;He S

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背景 弓形虫是一种专性细胞内寄生虫,可引起弓形虫病,严重威胁人类健康。目前还没有针对这种感染的慢性囊肿阶段的药物;因此,开发有效的疫苗将是一个重要的进展。天冬氨酸蛋白酶在T.弓形虫生活史该寄生虫具有四个天冬氨酸蛋白酶编码基因,它们被称为toxomepsin 1、2、3和5(分别为TgASP 1、2、3和5)。 方法 生物信息学方法使我们能够确定几个有前途的线性B细胞表位和潜在的Th细胞表位TgASP 1,从而支持其作为抗弓形虫病的DNA疫苗的潜力。我们在大肠杆菌中表达了TgASP 1,并将纯化的蛋白免疫BALB/c小鼠。获得的抗体用于确定TgASP 1在寄生虫中的位置。我们还制备了TgASP 1 DNA疫苗构建体,并评估了其对小鼠抵抗T. RH强毒株感染的保护水平。刚地。 结果 TgASP 1似乎是一种主要位于T.弓形虫速殖子对它作为DNA疫苗的潜力的研究表明,它在小鼠中引起强烈的体液和细胞免疫应答,并且这些应答由Th-1细胞介导。用疫苗免疫的小鼠在用T.弓形虫RH速殖子比用PBS或空载体对照免疫的那些多。 结论 TgASP 1是一种新的候选DNA疫苗,值得进一步研究。
Background Toxoplasma gondii is an obligate intracellular parasite that can pose a serious threat to human health by causing toxoplasmosis. There are no drugs that target the chronic cyst stage of this infection; therefore, development of an effective vaccine would be an important advance. Aspartic proteases play essential roles in the T. gondii lifecycle. The parasite has four aspartic protease encoding genes, which are called toxomepsin 1, 2, 3 and 5 (TgASP1, 2, 3 and 5, respectively). Methods Bioinformatics approaches have enabled us to identify several promising linear-B cell epitopes and potential Th-cell epitopes on TgASP1, thus supporting its potential as a DNA vaccine against toxoplasmosis. We expressed TgASP1 in Escherichia coli and used the purified protein to immunize BALB/c mice. The antibodies obtained were used to determine where TgASP1 was localized in the parasite. We also made a TgASP1 DNA vaccine construct and evaluated it for the level of protection conferred to mice against infection with the virulent RH strain of T. gondii. Results TgASP1 appears to be a membrane protein located primarily at the tip of the T. gondii tachyzoite. Investigation of its potential as a DNA vaccine showed that it elicited strong humoral and cellular immune responses in mice, and that these responses were mediated by Th-1 cells. Mice immunized with the vaccine had greater levels of protection against mortality following challenge with T. gondii RH tachyzoites than did those immunized with PBS or the empty vector control. Conclusions TgASP1 is a novel candidate DNA vaccine that merits further investigation.
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