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鉴定截断型 MrpH.FliC 作为一种疫苗候选物针对由奇异变形杆菌引起的尿路感染的免疫原性。

Determination immunogenic property of truncated MrpH.FliC as a vaccine candidate against urinary tract infections caused by Proteus mirabilis.

机构信息

Department of Molecular Biology, Pasteur Institute of Iran, Pasteur Ave., Tehran 13164, Iran.

Department of Molecular Biology, Pasteur Institute of Iran, Pasteur Ave., Tehran 13164, Iran.

出版信息

Microb Pathog. 2018 Jan;114:99-106. doi: 10.1016/j.micpath.2017.11.015. Epub 2017 Nov 11.

Abstract

Proteus mirabilis is common cause of urinary tract infections (UTIs) especially in complicated UTIs which are resistant to antibiotic therapy, Consequently, an ideal vaccine is inevitably required. The N-terminal domain of MrpH (Truncated form of MrpH) lies between the most critical antigens of P. mirabilis to consider as vaccine candidate. FliC of Salmonella typhimurium induces several pathways of immunity system, which leads to produce antibody and cytokines. In this study, adjuvant properties of FliC and efficacy of truncated MrpH as important antigen, in tMrpH.FliC were determined in in vitro and in vivo circumstances. Three proteins including: FliC, MrpH and tMrpH.FliC were injected to mice and subsequently sera and supernatant of cell culture were collected to evaluate different immune responses. According to our findings, tMrpH.FliC could stimulate both humoral and cellular immune responses, so that serum IgG, urine IgA, IL.4, IFN-γ and IL.17 were increased significantly in comparison to MrpH and FliC alone, this augmentation was considerable. Results showed significant decrease of bacterial load in all of the challenged groups compared to the control group, although this protective effect was the highest in mice vaccinated with tMrpH.FliC. Our results showed truncated MrpH, without an unwanted domain is an ideal vaccine target and FliC, as adjuvant, increases its immunogenic property. Thus, fusion protein tMrpH.FliC can be considered as promising vaccine against P. mirabilis.

摘要

奇异变形杆菌是尿路感染(UTI)的常见病因,尤其是在对抗生素治疗有抗药性的复杂 UTI 中。因此,不可避免地需要一种理想的疫苗。MrpH 的 N 端结构域(MrpH 的截断形式)位于奇异变形杆菌最重要的抗原之间,可作为候选疫苗。鼠伤寒沙门氏菌的 FliC 可诱导免疫系统的多个途径,从而导致产生抗体和细胞因子。在这项研究中,在体外和体内环境中确定了 FliC 的佐剂特性和作为重要抗原的截断 MrpH(tMrpH).FliC 的功效。将三种蛋白质(包括 FliC、MrpH 和 tMrpH.FliC)注射到小鼠中,然后收集血清和细胞培养上清液以评估不同的免疫反应。根据我们的发现,tMrpH.FliC 可以刺激体液和细胞免疫反应,因此与单独的 MrpH 和 FliC 相比,血清 IgG、尿液 IgA、IL.4、IFN-γ 和 IL.17 显著增加,这种增加是相当可观的。与对照组相比,所有受挑战组的细菌载量均显著下降,尽管在接种 tMrpH.FliC 的小鼠中,这种保护作用最高。我们的结果表明,截断的 MrpH 没有不需要的结构域,是一种理想的疫苗靶标,而 FliC 作为佐剂可提高其免疫原性。因此,融合蛋白 tMrpH.FliC 可以被认为是对抗奇异变形杆菌的有前途的疫苗。

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