Heidarinia Hana, Tajbakhsh Elahe, Bahrami Yadollah, Rostamian Mosayeb
Department of Microbiology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran.
Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
AMB Express. 2025 Jul 12;15(1):103. doi: 10.1186/s13568-025-01913-6.
Acinetobacter baumannii is a significant cause of hospital-acquired infections and is often resistant to multiple antibiotics. In this study, we designed a multi-epitope vaccine candidate using the outer membrane protein K (OmpK) of A. baumannii. T-cell and B-cell epitopes were predicted, and the best epitopes were selected for multi-epitope design. For selecting the best epitopes, many in silico studies, as well as molecular docking of epitope-HLAs, were performed. The multi-epitope was designed using β-defensin as an adjuvant, PADRE sequence as an immunogenicity enhancer, and appropriate linkers. The tertiary structure of the multi-epitope was obtained using modeling and several molecular dynamics (MD)-based refinements. The sequence and/or 3D model of the multi-epitope was investigated for physicochemical, structural, in silico cloning, conformational B epitope prediction, immune response simulation, molecular docking for assay binding to toll-like receptors (TLRs), and deformability studies. The results showed that the multi-epitope construct is favorable in the case of immunogenicity, physicochemical properties, structure, binding to TLRs, solubility, stability, toxicity, allergenicity, and cross-reactivity. This multi-epitope vaccine candidate has the potential to elicit multiple immune responses against A. baumannii. However, in vitro and in vivo experimental tests are needed to validate its efficacy as a potential vaccine candidate.
鲍曼不动杆菌是医院获得性感染的重要病因，且常常对多种抗生素耐药。在本研究中，我们利用鲍曼不动杆菌的外膜蛋白K（OmpK）设计了一种多表位疫苗候选物。对T细胞和B细胞表位进行了预测，并选择最佳表位用于多表位设计。为了选择最佳表位，进行了许多计算机模拟研究以及表位与人类白细胞抗原（HLA）的分子对接。多表位的设计使用β-防御素作为佐剂、PADRE序列作为免疫原性增强剂以及合适的连接子。通过建模和基于分子动力学（MD）的多次优化获得了多表位的三级结构。对多表位的序列和/或三维模型进行了物理化学、结构、计算机克隆、构象性B表位预测、免疫反应模拟、与Toll样受体（TLR）结合的分子对接分析以及可变形性研究。结果表明，多表位构建体在免疫原性、物理化学性质、结构、与TLR的结合、溶解性、稳定性、毒性、致敏性和交叉反应性方面表现良好。这种多表位疫苗候选物有可能引发针对鲍曼不动杆菌的多种免疫反应。然而，需要进行体外和体内实验测试来验证其作为潜在疫苗候选物的有效性。
