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针对内脏利什曼病的单抗原 Gp63、多表位和多表位 HSP70 DNA 疫苗的免疫原性和疗效的实验性小鼠模型研究。

Immunogenicity and efficacy of single antigen Gp63, polytope and polytopeHSP70 DNA vaccines against visceral Leishmaniasis in experimental mouse model.

机构信息

Department of Parasitology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

出版信息

PLoS One. 2009 Dec 2;4(12):e7880. doi: 10.1371/journal.pone.0007880.

Abstract

Polytope approach of genetic immunization is a promising strategy for the prevention of infectious disease as it is capable of generating effective cell mediated immunity by delivering the T cell epitopes assembled in series. Leishmaniasis is a significant world wide health problem for which no vaccine exists. In this study we have compared immunogenicity and efficacy of three types of DNA vaccines: single antigen Gp63 (Gp63/pcDNA), polytope (Poly/pcDNA) and Polytope fused with hsp70 (Poly/hsp/pcDNA) against visceral leishmaniasis in susceptible BALB/c mice. Mice vaccinated with these plasmids generated strong Th1 immune response as seen by dominating IFN-gamma over IL-10 cytokine. Interestingly, cytotoxic responses generated by polytope DNA plasmid fused with hsp70 of Leishmania donovani were significantly higher when compared to polytope and single antigen Gp63 vaccine. Challenge studies revealed that the parasite load in liver and spleen was significantly lower with Poly/hsp/pcDNA vaccination compared to other vaccines. Therefore, our study indicates that polytope DNA vaccine is a feasible, practical and effective approach for visceral leishmaniasis.

摘要

多面体基因免疫是一种很有前途的传染病预防策略,因为它能够通过递呈串联组装的 T 细胞表位来产生有效的细胞免疫。利什曼病是一个重大的全球性健康问题,但目前还没有疫苗。在这项研究中,我们比较了三种类型的 DNA 疫苗:单一抗原 Gp63(Gp63/pcDNA)、多面体(Poly/pcDNA)和多面体融合 hsp70(Poly/hsp/pcDNA)对易感 BALB/c 小鼠内脏利什曼病的免疫原性和疗效。用这些质粒免疫的小鼠产生了强烈的 Th1 免疫反应,表现为 IFN-γ 细胞因子显著高于 IL-10。有趣的是,与多面体和单一抗原 Gp63 疫苗相比,多面体 DNA 质粒与利什曼原虫的 hsp70 融合产生的细胞毒性反应显著更高。挑战研究表明,与其他疫苗相比,Poly/hsp/pcDNA 疫苗接种可显著降低肝脏和脾脏中的寄生虫负荷。因此,我们的研究表明,多面体 DNA 疫苗是一种可行、实用和有效的内脏利什曼病预防方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b05b/2780826/5ce9d9aaa41f/pone.0007880.g001.jpg

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