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通过反向疫苗学和基因组学方法鉴定出的用于控制鲍曼不动杆菌血清型的新型B细胞疫苗候选物。

Putative novel B-cell vaccine candidates identified by reverse vaccinology and genomics approaches to control Acinetobacter baumannii serotypes.

作者信息

Beiranvand Sheida, Doosti Abbas, Mirzaei Seyed Abbas

机构信息

Department of Biology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran.

Biotechnology Research Center, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran.

出版信息

Infect Genet Evol. 2021 Dec;96:105138. doi: 10.1016/j.meegid.2021.105138. Epub 2021 Nov 15.

Abstract

In the last decade, Multi-drug resistance (MDR)-associated infections of Acinetobacter baumannii have grown worldwide. A cost-effective preventative strategy against this bacterium is vaccination. This study has presented five novel vaccine candidates against A. baumannii produced using the reverse vaccinology method. BLASTn was done to identify the most conserved antigens. PSORTb 3.0.2 was run to predict the subcellular localization of the proteins. The initial screening and antigenicity evaluation were performed using Vaxign. The ccSOL omics was also employed to predict protein solubility. The cross-membrane localization of the protein was predicted using PRED-TMBB. B cell epitope prediction was made for immunogenicity using the IEDB and BepiPred-2.0 database. Eventually, BLASTp was done to verify the extent of similarity to the human proteome to exclude the possibility of autoimmunity. Proteins failing to comply with the set parameters were filtered at each step. In silico, potential vaccines against 21 A. baumannii strains were identified using reverse vaccinology and subtractive genomic techniques. Based on the above criteria, out of the initial 15 A. baumannii proteins selected for screening, nine exposed/secreted/membrane proteins, i.e., Pfsr, LptE, OmpH, CarO, CsuB, CdiB, MlaA, FhuE, and were the most promising candidates. Their solubility and antigenicity were also examined and found to be more than 0.45 and 0.6, respectively. Based on the results, LptE was selected with the highest average antigenic score of 1.043 as the best protein, followed by FimF and Pfsr with scores of 1.022 and 1.014, respectively. In the end, five proteins were verified as promising candidates. Overall, the targets identified herein may be utilized in future strategies to control A. baumannii worldwide.

摘要

在过去十年中,鲍曼不动杆菌的多重耐药(MDR)相关感染在全球范围内不断增加。针对这种细菌的一种具有成本效益的预防策略是接种疫苗。本研究提出了五种使用反向疫苗学方法生产的针对鲍曼不动杆菌的新型候选疫苗。进行BLASTn以鉴定最保守的抗原。运行PSORTb 3.0.2来预测蛋白质的亚细胞定位。使用Vaxign进行初步筛选和抗原性评估。还采用ccSOL组学来预测蛋白质的溶解度。使用PRED-TMBB预测蛋白质的跨膜定位。使用IEDB和BepiPred-2.0数据库对免疫原性进行B细胞表位预测。最后,进行BLASTp以验证与人类蛋白质组的相似程度,以排除自身免疫的可能性。在每个步骤中,对不符合设定参数的蛋白质进行筛选。通过反向疫苗学和消减基因组技术,在计算机模拟中鉴定出针对21种鲍曼不动杆菌菌株的潜在疫苗。基于上述标准,在最初选择用于筛选的15种鲍曼不动杆菌蛋白质中,九种暴露/分泌/膜蛋白,即Pfsr、LptE、OmpH、CarO、CsuB、CdiB、MlaA、FhuE,是最有前景的候选者。还检查了它们的溶解度和抗原性,发现分别大于0.45和0.6。根据结果,选择平均抗原得分最高为1.043的LptE作为最佳蛋白质,其次是FimF和Pfsr,得分分别为1.022和1.014。最后,五种蛋白质被确认为有前景的候选者。总体而言,本文确定的靶点可用于未来全球控制鲍曼不动杆菌的策略中。

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