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刚地弓形虫蛋白二硫键异构酶(TgPDI)是一种针对弓形虫病的新型候选疫苗。

Toxoplasma gondii protein disulfide isomerase (TgPDI) is a novel vaccine candidate against toxoplasmosis.

机构信息

Research Institute of Medical Parasitology, Shanxi Medical University, Taiyuan, Shanxi, PR China.

出版信息

PLoS One. 2013 Aug 15;8(8):e70884. doi: 10.1371/journal.pone.0070884. eCollection 2013.

Abstract

Toxoplasma gondii is a ubiquitous protozoan parasite that can infect all warm-blooded animals, including both mammals and birds. Protein disulfide isomerase (PDI) localises to the surface of T. gondii tachyzoites and modulates the interactions between parasite and host cells. In this study, the protective efficacy of recombinant T. gondii PDI (rTgPDI) as a vaccine candidate against T. gondii infection in BALB/c mice was evaluated. rTgPDI was expressed and purified from Escherichia coli. Five groups of animals (10 animals/group) were immunised with 10, 20, 30, 40 μg of rTgPDI per mouse or with PBS as a control group. All immunisations were performed via the nasal route at 1, 14 and 21 days. Two weeks after the last immunisation, the immune responses were evaluated by lymphoproliferative assays and by cytokine and antibody measurements. The immunised mice were challenged with tachyzoites of the virulent T. gondii RH strain on the 14th day after the last immunisation. Following the challenge, the tachyzoite loads in tissues were assessed, and animal survival time was recorded. Our results showed that the group immunised with 30 μg rTgPDI showed significantly higher levels of specific antibodies against the recombinant protein, a strong lymphoproliferative response and significantly higher levels of IgG2a, IFN-gamma (IFN-γ), IL-2 and IL-4 production compared with other doses and control groups. While no changes in IL-10 levels were detected. After being challenged with T. gondii tachyzoites, the numbers of tachyzoites in brain and liver tissues from the rTgPDI group were significantly reduced compared with those of the control group, and the survival time of the mice in the rTgPDI group was longer than that of mice in the control group. Our results showed that immunisation with rTgPDI elicited a protective immune reaction and suggested that rTgPDI might represent a promising vaccine candidate for combating toxoplasmosis.

摘要

刚地弓形虫是一种普遍存在的原生动物寄生虫,可感染所有温血动物,包括哺乳动物和鸟类。蛋白二硫键异构酶(PDI)定位于刚地弓形虫速殖子的表面,并调节寄生虫和宿主细胞之间的相互作用。在这项研究中,评估了重组刚地弓形虫 PDI(rTgPDI)作为刚地弓形虫感染疫苗候选物在 BALB/c 小鼠中的保护效力。rTgPDI 从大肠杆菌中表达和纯化。将五组动物(每组 10 只)用 10、20、30、40μg rTgPDI 免疫每只小鼠,或用 PBS 作为对照组。所有免疫均通过鼻内途径在第 1、14 和 21 天进行。最后一次免疫后两周,通过淋巴细胞增殖测定和细胞因子及抗体测量评估免疫反应。在最后一次免疫后第 14 天,用强毒刚地弓形虫 RH 株速殖子对免疫小鼠进行攻毒。攻毒后,评估组织中的速殖子载量,并记录动物的存活时间。结果显示,用 30μg rTgPDI 免疫的组显示针对重组蛋白的特异性抗体水平显著升高,淋巴细胞增殖反应强烈,IgG2a、IFN-γ(IFN-γ)、IL-2 和 IL-4 的产生水平显著升高与其他剂量和对照组相比。而 IL-10 水平没有变化。用刚地弓形虫速殖子攻毒后,rTgPDI 组脑组织和肝组织中的速殖子数量明显低于对照组,rTgPDI 组小鼠的存活时间长于对照组。结果表明,rTgPDI 免疫引起了保护性免疫反应,提示 rTgPDI 可能是一种有前途的抗弓形虫病疫苗候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a3d/3744524/6c2232527365/pone.0070884.g001.jpg

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