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表达 GRA16 的 DNA 疫苗诱导的慢性感染抗性

Resistance to Chronic Infection Induced by a DNA Vaccine Expressing GRA16.

机构信息

State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu 730046, China.

College of Animal Science, Fujian Agriculture and Forestry University, Fuzhou, Fujian 350002, China.

出版信息

Biomed Res Int. 2017;2017:1295038. doi: 10.1155/2017/1295038. Epub 2017 Aug 10.

DOI:10.1155/2017/1295038
PMID:28875149
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5569751/
Abstract

can infect all warm-blooded animals including human beings. dense granule protein 16 (TgGRA16) as a crucial virulence factor could modulate the host gene expression. Here, a DNA vaccine expressing TgGRA16 was constructed to explore the protective efficacy against infection in Kunming mice. The immune responses induced by pVAX-GRA16 were also evaluated. Mice immunized with pVAX-GRA16 could elicit higher levels of specific IgG antibody and strong cellular response compared to those in controls. The DNA vaccination significantly increased the levels of cytokines (IFN-, IL-2, IL-4, and IL-10) and the percentages of CD4+ and CD8+ T cells in mice. After lethal challenge, mice immunized with pVAX-GRA16 (8.4 ± 0.78 days) did not show a significant longer survival time than that in controls (7.1 ± 0.30 days) ( > 0.05). However, in chronic toxoplasmosis model (administration of 10 brain cysts of PRU strain orally), numbers of tissue cysts in mice immunized with pVAX-GRA16 were significantly reduced compared to those in controls ( < 0.05) and the rate of reduction could reach 43.89%. The results indicated that the TgGRA16 would be a promising vaccine candidate for further development of effective epitope-based vaccines against chronic infection in mice.

摘要

刚地弓形虫可以感染所有温血动物,包括人类。致密颗粒蛋白 16(TgGRA16)作为一种关键的毒力因子,可以调节宿主基因表达。本研究构建了表达 TgGRA16 的 DNA 疫苗,以探索其在昆明小鼠中的保护效果。还评估了 pVAX-GRA16 诱导的免疫反应。与对照组相比,pVAX-GRA16 免疫的小鼠能诱导更高水平的特异性 IgG 抗体和强烈的细胞反应。DNA 疫苗接种显著增加了细胞因子(IFN-γ、IL-2、IL-4 和 IL-10)和 CD4+和 CD8+T 细胞的比例。在致死性挑战后,pVAX-GRA16 免疫的小鼠(8.4±0.78 天)的存活时间与对照组(7.1±0.30 天)相比没有显著延长(>0.05)。然而,在慢性弓形虫病模型(口服 10 个 PRU 株脑囊)中,pVAX-GRA16 免疫的小鼠组织囊数量明显低于对照组(<0.05),减少率可达 43.89%。结果表明,TgGRA16 可能成为进一步开发针对慢性弓形虫感染的有效表位疫苗的候选疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb0a/5569751/7cda1f8c082b/BMRI2017-1295038.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb0a/5569751/0d2a6f2af729/BMRI2017-1295038.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb0a/5569751/7cda1f8c082b/BMRI2017-1295038.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb0a/5569751/0d2a6f2af729/BMRI2017-1295038.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb0a/5569751/7cda1f8c082b/BMRI2017-1295038.002.jpg

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