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新型基因佐剂重组 DNA 疫苗诱导的弓形虫保护性免疫应答。

Protective immune response against Toxoplasma gondii elicited by a recombinant DNA vaccine with a novel genetic adjuvant.

机构信息

Department of Parasitology, Shandong University School of Medicine, Jinan, Shandong, PR China.

出版信息

Vaccine. 2012 Feb 27;30(10):1800-6. doi: 10.1016/j.vaccine.2012.01.004. Epub 2012 Jan 10.

DOI:10.1016/j.vaccine.2012.01.004
PMID:22240340
Abstract

Previous immunological studies from our laboratory have demonstrated the potential role of Toxoplasma gondii antigens SAG1 and GRA2 as vaccine candidates. To further evaluate the vaccine's effects, a series of recombinant DNA vaccines pVAX1-SAG1, pVAX1-GRA2 and pVAX1-SAG1-GRA2, termed pSAG1, pGRA2 and pSAG1-GRA2, respectively, were constructed. A plasmid pVAX1-S/PreS2, termed pSPreS2 encoding hepatitis B virus (HBV) surface antigen (HBsAg) S and PreS2 as a novel genetic adjuvant, was also constructed. The expression abilities of those DNA plasmids were examined in HFF cells by Western blotting. Then BALB/c mice were intramuscularly immunized with DNA plasmids and followed by challenging with the highly virulent T. gondii RH strain. The results demonstrated that the recombinant DNA vaccine pSAG1-GRA2 was capable of eliciting high levels of antibodies, a Th1 type of immune response with significant production of IFN-γ and low levels of IL-4 or IL-10 in BALB/c mice, and partial protection against the acute phase of toxoplasmosis as compared to pSAG1, pGRA2 and controls. In addition, the adjuvant pSPreS2 formulated with DNA vaccine induced a Th1 type of immune response and therefore might be a novel genetic adjuvant to DNA vaccine for further investigation.

摘要

先前我们实验室的免疫研究表明,刚地弓形虫抗原 SAG1 和 GRA2 具有作为疫苗候选物的潜力。为了进一步评估疫苗的效果,构建了一系列重组 DNA 疫苗 pVAX1-SAG1、pVAX1-GRA2 和 pVAX1-SAG1-GRA2,分别命名为 pSAG1、pGRA2 和 pSAG1-GRA2。还构建了一个质粒 pVAX1-S/PreS2,称为 pSPreS2,其编码乙型肝炎病毒 (HBV) 表面抗原 (HBsAg) S 和 PreS2,作为一种新型遗传佐剂。通过 Western blot 检查了这些 DNA 质粒在 HFF 细胞中的表达能力。然后,用 DNA 质粒肌肉内免疫 BALB/c 小鼠,并用高毒力刚地弓形虫 RH 株进行攻毒。结果表明,与 pSAG1、pGRA2 和对照组相比,重组 DNA 疫苗 pSAG1-GRA2 能够在 BALB/c 小鼠中引起高水平的抗体,Th1 型免疫反应,显著产生 IFN-γ,IL-4 或 IL-10 水平较低,并对弓形虫病的急性阶段提供部分保护。此外,与 DNA 疫苗联合使用的佐剂 pSPreS2 诱导了 Th1 型免疫反应,因此可能是 DNA 疫苗的新型遗传佐剂,值得进一步研究。

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