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用一种新型免疫原性候选物(脲酶)进行皮下免疫可提供针对牛布鲁氏菌和羊布鲁氏菌感染的保护。

Subcutaneous immunization with a novel immunogenic candidate (urease) confers protection against Brucella abortus and Brucella melitensis infections.

作者信息

Abkar Morteza, Amani Jafar, Sahebghadam Lotfi Abbas, Nikbakht Brujeni Gholamreza, Alamian Saeed, Kamali Mehdi

机构信息

Department of Molecular Genetics, Faculty of Basic Sciences, Tarbiat Modares University, Tehran, Iran.

Applied Microbiology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.

出版信息

APMIS. 2015 Aug;123(8):667-75. doi: 10.1111/apm.12400. Epub 2015 May 2.

DOI:10.1111/apm.12400
PMID:25939375
Abstract

Brucellosis is a world prevalent endemic illness that is transmitted from domestic animals to humans. Brucella spp. exploits urease for survival in the harsh conditions of stomach during the gastrointestinal infection. In this study, we examined the immune response and the protection elicited by using recombinant Brucella urease (rUrease) vaccination in BALB/c mice. The urease gene was cloned in pET28a and the resulting recombinant protein was employed as subunit vaccine. Recombinant protein was administered subcutaneously and intraperitoneally. Dosage reduction was observed with subcutaneous (SC) vaccination when compared with intraperitoneal (IP) vaccination. rUrease induced mixed Th1-Th2 immune responses with high titers of specific IgG1 and IgG2a. In lymphocyte proliferation assay, splenocytes from IP and SC-vaccinated mice displayed a strong recall proliferative response with high amounts of IL-4, IL-12 and IFN-γ production. Vaccinated mice were challenged with virulent Brucella melitensis, B. abortus and B. suis. The SC vaccination route exhibited a higher degree of protection than IP vaccination (p value ≤ 0.05). Altogether, our results indicated that rUrease could be a useful antigen candidate for the development of subunit vaccines against brucellosis.

摘要

布鲁氏菌病是一种在世界范围内流行的地方病,可从家畜传播给人类。布鲁氏菌属利用脲酶在胃肠道感染期间在胃部的恶劣环境中生存。在本研究中,我们检测了在BALB/c小鼠中使用重组布鲁氏菌脲酶(rUrease)疫苗接种所引发的免疫反应和保护作用。脲酶基因被克隆到pET28a中,所得重组蛋白被用作亚单位疫苗。重组蛋白通过皮下和腹腔内给药。与腹腔内(IP)接种相比,皮下(SC)接种时观察到剂量减少。rUrease诱导了混合的Th1-Th2免疫反应,产生了高滴度的特异性IgG1和IgG2a。在淋巴细胞增殖试验中,来自IP和SC接种小鼠的脾细胞表现出强烈的回忆增殖反应,产生大量的IL-4、IL-12和IFN-γ。对接种疫苗的小鼠用强毒力的羊种布鲁氏菌、牛种布鲁氏菌和猪种布鲁氏菌进行攻毒。SC接种途径比IP接种表现出更高程度的保护作用(p值≤0.05)。总之,我们的结果表明rUrease可能是开发抗布鲁氏菌病亚单位疫苗的有用抗原候选物。

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