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评价新型鲍曼不动杆菌外膜蛋白 A 表位疫苗对肺炎克雷伯菌相关肺炎和脓毒症感染小鼠模型的作用。

Evaluationof the New Outer Membrane Protein A Epitope-based Vaccines for Mice Model of Acinetobacter baumannii Associated Pneumonia and Sepsis Infection.

机构信息

Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Iran J Allergy Asthma Immunol. 2021 Sep 28;20(5):537-549. doi: 10.18502/ijaai.v20i5.7404.

Abstract

Nosocomial infections caused by Acinetobacter baumannii (A. baumannii) nosocomial infections caused by Acinetobacter baumannii (A. baumannii) are considered as a global serious problem in hospitalized patients because of emerging antibiotic resistance. Immunotherapy approaches are promising to prevent such infections. In our previous study, five antigenic epitopes of outer membrane protein A (OmpA), as the most dangerous virulence molecule in A. baumanii, were predicted in silico. In this study, the investigators evaluated some immunological aspects of the peptides. Five peptides were separately injected into C5BL/6 mice; then the cytokine production (interleukin-4 and interferon-gamma) of splenocytes and opsonophagocytic activity of immunized serum were assessed. To identify the protective function of the peptides, animal models of sepsis and pneumonia infections were actively and passively immunized with selected peptides and pooled sera of immunized mice, respectively. Then, survival rates of them were compared with the non-infected controls. Based on the results, activated spleen cells in P127 peptide-immunized mice exhibited an increase level of IFN-γ compared with the other experimental groups, but not about the IL-4 concentration. The results of opsonophagocytic assay revealed an appropriate killing activity of produced antibodies against A. baumannii in a dose-dependent manner. Further, the survival rates of the mice under passive immunization with the immunized sera or active immunization with P127 peptide were significantly more than those in the control group. Moreover, the survival rate of the P127 peptide immunized group was considerably higher than that among the other peptide-immunized group. In conclusion, findings indicated that peptides derived from outer membrane protein-A can be used as a promising tool for designing the epitope-based vaccines against infections caused by A. baumannii.

摘要

鲍曼不动杆菌(A.baumannii)引起的医院获得性感染被认为是住院患者中一个全球性的严重问题,因为其出现了抗生素耐药性。免疫疗法在预防此类感染方面具有广阔的前景。在我们之前的研究中,通过计算机预测了外膜蛋白 A(OmpA)的五个抗原表位,该蛋白是 A.baumannii 中最危险的毒力分子。在本研究中,研究人员评估了这些肽的一些免疫学方面。将这 5 个肽分别注入 C5BL/6 小鼠体内;然后评估了脾细胞细胞因子产生(白细胞介素 4 和干扰素-γ)和免疫血清的调理吞噬活性。为了确定这些肽的保护功能,使用选定的肽和免疫小鼠的混合血清主动和被动免疫了败血症和肺炎感染的动物模型,然后比较了它们的存活率与未感染对照。结果表明,与其他实验组相比,P127 肽免疫小鼠的活化脾细胞 IFN-γ水平升高,但白细胞介素 4 浓度没有升高。调理吞噬测定的结果表明,针对 A.baumannii 的产生抗体具有适当的杀伤活性,呈剂量依赖性。此外,用免疫血清进行被动免疫或用 P127 肽进行主动免疫的小鼠的存活率明显高于对照组。此外,P127 肽免疫组的存活率明显高于其他肽免疫组。总之,这些发现表明,来源于外膜蛋白-A 的肽可以作为设计针对 A.baumannii 感染的基于表位疫苗的有前途的工具。

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