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采用反向疫苗学方法鉴定鲍曼不动杆菌蛋白质的抗原特性作为新型潜在疫苗候选物

Identification of Antigenic Properties of Acinetobacter baumannii Proteins as Novel Putative Vaccine Candidates Using Reverse Vaccinology Approach.

作者信息

Piri-Gharaghie Tohid, Doosti Abbas, Mirzaei Seyed Abbas

机构信息

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

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

出版信息

Appl Biochem Biotechnol. 2022 Oct;194(10):4892-4914. doi: 10.1007/s12010-022-03995-5. Epub 2022 Jun 7.

Abstract

Multidrug-resistant Acinetobacter baumannii (A. baumannii) infections are becoming more prevalent all over the world. As a cost-effective and preventative method, vaccination seems to be required against this bacterium. In the present study, subtractive proteomics along with reverse vaccinology approaches was used to predict suitable therapeutics against A. baumannii. Using the Vaxign online tool, we studied over 35 genomes of A. baumannii strains and chose outer membrane and secreted proteins of A. baumannii 1656-2 as possible vaccine candidates. Then, investigations were performed on the immunogenicity, antigenic characteristics, physicochemical properties, B-cell and MHC class I, and MHC class II molecules epitope densities of proteins. After optimizing the codon of the proteins, the pcDNA3.1( +) expression construct was designed and the immunogenicity, allergenicity, and physicochemical properties of the vaccine construct were predicted. Hcp and OmpC proteins were predicted as extracellular and outer membrane proteins, respectively. These proteins interact with 10 other proteins to form a network of protein interactions with virulence properties. Immunoassays of Hcp and OmpC proteins showed antigenicity of 0.88 and 0.79, respectively. These proteins have 5 structural cell epitope points and 5 linear B epitope points. They are also able to bind to different HLA alleles of MCH class I/class II as selected immunogenic proteins and designed non-allergenic structures with solubility of 0.650 and immunogenicity score of 0.91. The results of this "in silico" study indicate high specificity and the development of a significant humoral and cellular immune response. It can be concluded that the Hcp and OmpC dual vaccine construct is one of the promising candidates against A. baumannii. The findings of this "in silico" study show excellent specificity and the emergence of a substantial humoral and cellular immune response. This is a computer-based study that needs to be tested in vitro and in vivo to corroborate the conclusions of the vaccine design procedures.

摘要

多重耐药鲍曼不动杆菌感染在全球范围内正变得越来越普遍。作为一种经济有效的预防方法,似乎需要针对这种细菌进行疫苗接种。在本研究中,采用消减蛋白质组学和反向疫苗学方法来预测针对鲍曼不动杆菌的合适治疗方法。使用Vaxign在线工具,我们研究了超过35个鲍曼不动杆菌菌株的基因组,并选择鲍曼不动杆菌1656 - 2的外膜蛋白和分泌蛋白作为可能的疫苗候选物。然后,对这些蛋白质的免疫原性、抗原特性、理化性质、B细胞以及MHC I类和MHC II类分子表位密度进行了研究。在对蛋白质密码子进行优化后,设计了pcDNA3.1( +)表达构建体,并预测了疫苗构建体的免疫原性、致敏性和理化性质。Hcp和OmpC蛋白分别被预测为细胞外蛋白和外膜蛋白。这些蛋白质与其他10种蛋白质相互作用,形成具有毒力特性的蛋白质相互作用网络。对Hcp和OmpC蛋白的免疫分析显示其抗原性分别为0.88和0.79。这些蛋白质具有5个结构性细胞表位点和5个线性B表位点。作为选定的免疫原性蛋白质,它们还能够与MCH I类/II类的不同HLA等位基因结合,并设计出具有0.650溶解度和0.91免疫原性评分的非致敏结构。这项“虚拟”研究结果表明具有高特异性,并能产生显著的体液和细胞免疫反应。可以得出结论,Hcp和OmpC双疫苗构建体是对抗鲍曼不动杆菌的有前景的候选物之一。这项“虚拟”研究结果显示出优异的特异性,并出现了大量的体液和细胞免疫反应。这是一项基于计算机模拟的研究,需要在体外和体内进行测试以证实疫苗设计程序的结论。

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