Rafi Md Oliullah, Al-Khafaji Khattab, Mandal Santi M, Meghla Nigar Sultana, Biswas Polash Kumar, Rahman Md Shahedur
Bioinformatics and Microbial Biotechnology Laboratory, Department of Genetic Engineering and Biotechnology, Jashore University of Science and Technology, Jashore, 7408 Bangladesh.
Department of Genetic Engineering and Biotechnology, Jashore University of Science and Technology, Jashore, 7408 Bangladesh.
Netw Model Anal Health Inform Bioinform. 2023;12(1):21. doi: 10.1007/s13721-023-00416-3. Epub 2023 Apr 19.
Community-acquired pneumonia is primarily caused by and , two pathogens that have high morbidity and mortality rates. This is largely due to bacterial resistance development against current antibiotics and the lack of effective vaccines. The objective of this work was to develop an immunogenic multi-epitope subunit vaccine capable of eliciting a robust immune response against and . The targeted proteins were the pneumococcal surface proteins (PspA and PspC) and choline-binding protein (CbpA) of and the outer membrane proteins (OmpA and OmpW) of . Different computational approaches and various immune filters were employed for designing a vaccine. The immunogenicity and safety of the vaccine were evaluated by utilizing many physicochemical and antigenic profiles. To improve structural stability, disulfide engineering was applied to a portion of the vaccine structure with high mobility. Molecular docking was performed to examine the binding affinities and biological interactions at the atomic level between the vaccine and Toll-like receptors (TLR2 and 4). Further, the dynamic stabilities of the vaccine and TLRs complexes were investigated by molecular dynamics simulations. While the immune response induction capability of the vaccine was assessed by the immune simulation study. Vaccine translation and expression efficiency was determined through an in silico cloning experiment utilizing the pET28a(+) plasmid vector. The obtained results revealed that the designed vaccine is structurally stable and able to generate an effective immune response to combat pneumococcal infection.
The online version contains supplementary material available at 10.1007/s13721-023-00416-3.
社区获得性肺炎主要由[两种病原体名称]引起，这两种病原体具有较高的发病率和死亡率。这在很大程度上是由于细菌对当前抗生素产生耐药性以及缺乏有效的疫苗。这项工作的目的是开发一种具有免疫原性的多表位亚单位疫苗，能够引发针对[两种病原体名称]的强大免疫反应。靶向蛋白是[病原体名称]的肺炎球菌表面蛋白（PspA和PspC）以及胆碱结合蛋白（CbpA）和[另一种病原体名称]的外膜蛋白（OmpA和OmpW）。采用不同的计算方法和各种免疫筛选来设计疫苗。利用多种物理化学和抗原特性评估疫苗的免疫原性和安全性。为提高结构稳定性，对具有高流动性的疫苗结构部分应用了二硫键工程。进行分子对接以研究疫苗与Toll样受体（TLR2和4）在原子水平上的结合亲和力和生物相互作用。此外，通过分子动力学模拟研究疫苗和TLR复合物的动态稳定性。同时，通过免疫模拟研究评估疫苗诱导免疫反应的能力。利用pET28a(+)质粒载体通过计算机克隆实验确定疫苗的翻译和表达效率。获得的结果表明，设计的疫苗结构稳定，能够产生有效的免疫反应来对抗肺炎球菌感染。
在线版本包含可在10.1007/s13721-023-00416-3获取的补充材料。
