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鲍曼不动杆菌外膜蛋白a抗原肽作为免疫小鼠疫苗候选物的计算机辅助设计与评估

In Silico Design and Evaluation of Acinetobacter baumannii Outer Membrane Protein a Antigenic Peptides As Vaccine Candidate in Immunized Mice.

作者信息

Mehdinejadiani Kobra, Bandehpour Mojgan, Hashemi Ali, Ranjbar Mohammad Mehdi, Taheri Sodabeh, Jalali Seyed Amir, Mosaffa Nariman

机构信息

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

Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Iran J Allergy Asthma Immunol. 2019 Nov 10;18(6):655-663. doi: 10.18502/ijaai.v18i6.2178.

Abstract

Acinetobacter baumannii is a Gram-negative bacterium that has recently been identified as a leading nosocomial pathogen. Infections by this pathogen result in significant mortality due to antibiotic resistance. An effective vaccine would help alleviate the burden of disease incurred by this pathogen; however, there are currently no licensed vaccines offering protection against Acinetobacter baumannii infection. In this study, considering the fact that outer membrane protein A is one of the most promising vaccine candidates, we predicted T cell and B cell epitopes on this protein using sequence-based epitope prediction tools and determined whether or not mice immunized with these peptides induce an immune response. We selected consensus epitopes including five peptides in different tools with the highest score. 48 female C5BL/6 SPF injected subcutaneously with the peptides (peptide1 to peptide 5 separately) in 100 μL of the solution and sham groups received adjuvant and PBS alone on the same schedule: on day 0 (primary dose) and two booster doses were administered on days 14 and 28. At the end of time, animals euthanized by Isoflurane, and collected sera for assessment of specific antibodies against each peptide by ELISA (Enzyme-linked immunosorbent assay). Immunization of mice showed one of the novel synthetic peptides (peptide 1 (24-50 amino acids)) elicited immune responses. We conclude to combine theoretical methods of epitope prediction and evaluating the potential of immunogenicity for developing vaccines is important.

摘要

鲍曼不动杆菌是一种革兰氏阴性细菌,最近被确认为主要的医院病原体。这种病原体引起的感染由于抗生素耐药性导致显著的死亡率。一种有效的疫苗将有助于减轻这种病原体所带来的疾病负担;然而,目前尚无获得许可的针对鲍曼不动杆菌感染的疫苗。在本研究中,考虑到外膜蛋白A是最有前景的疫苗候选物之一,我们使用基于序列的表位预测工具预测了该蛋白上的T细胞和B细胞表位,并确定用这些肽免疫的小鼠是否诱导免疫反应。我们在不同工具中选择了得分最高的包括五个肽的共有表位。48只雌性C5BL/6无特定病原体小鼠皮下注射100 μL溶液中的肽(分别为肽1至肽5),假手术组在相同时间按照相同方案单独接受佐剂和PBS:在第0天(初次剂量)以及在第14天和第28天给予两次加强剂量。在实验结束时,通过异氟烷对动物实施安乐死,并收集血清通过酶联免疫吸附测定(ELISA)评估针对每种肽的特异性抗体。小鼠免疫显示其中一种新型合成肽(肽1(24 - 50个氨基酸))引发了免疫反应。我们得出结论,结合表位预测的理论方法并评估疫苗开发的免疫原性潜力很重要。

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