Alshabrmi Fahad M, Alrumaihi Faris, Alrasheedi Sahar Falah, Al-Megrin Wafa Abdullah I, Almatroudi Ahmad, Allemailem Khaled S
Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi Arabia.
Department of Laboratory and Blood Bank, King Saud Hospital, Unaizah 56437, Saudi Arabia.
Vaccines (Basel). 2022 Jul 15;10(7):1127. doi: 10.3390/vaccines10071127.
Antimicrobial resistance has become a significant health issue because of the misuse of antibiotics in our daily lives, resulting in high rates of morbidity and mortality. is a rod-shaped, Gram-negative and facultative anaerobic bacteria. The medical community has emphasized 's possible association with gastroenteritis. As of now, there is no licensed vaccine for , and as such, computer aided vaccine design approaches could be an ideal approach to highlight the potential vaccine epitopes against this bacteria. By using bacterial pan-genome analysis (BPGA), we were able to study the entire proteomes of with the aim of developing a vaccine. Based on the analysis, 20,370 proteins were identified as core proteins, which were further used in identifying potential vaccine targets based on several vaccine candidacy parameters. The prioritized vaccine targets against the bacteria are; type 1 fimbrial protein, flagellar hook length control protein (FliK), flagellar hook associated protein (FlgK), curli production assembly/transport protein (CsgF), fimbria/pilus outer membrane usher protein, fimbria/pilus outer membrane usher protein, molecular chaperone, flagellar filament capping protein (FliD), TonB-dependent hemoglobin /transferrin/lactoferrin family receptor, Porin (OmpA), flagellar basal body rod protein (FlgF) and flagellar hook-basal body complex protein (FliE). During the epitope prediction phase, different antigenic, immunogenic, non-Allergenic, and non-Toxic epitopes were predicted for the above-mentioned proteins. The selected epitopes were combined to generate a multi-epitope vaccine construct and a cholera toxin B subunit (adjuvant) was added to enhance the vaccine's antigenicity. Downward analyses of vaccines were performed using a vaccine three-dimensional model. Docking studies have confirmed that the vaccine strongly binds with MHC-I, MHC-II, and TLR-4 immune cell receptors. Additionally, molecular dynamics simulations confirmed that the vaccine epitopes were exposed to nature and to the host immune system and interpreted strong intermolecular binding between the vaccine and receptors. Based on the results of the study, the model vaccine construct seems to have the capacity to produce protective immune responses in the host, making it an attractive candidate for further in vitro and in vivo studies.
由于日常生活中抗生素的滥用，抗菌药物耐药性已成为一个重大的健康问题，导致高发病率和高死亡率。[细菌名称]是一种杆状、革兰氏阴性兼性厌氧菌。医学界已强调[细菌名称]可能与肠胃炎有关。截至目前，尚无针对[细菌名称]的许可疫苗，因此，计算机辅助疫苗设计方法可能是突出针对这种细菌的潜在疫苗表位的理想方法。通过使用细菌泛基因组分析（BPGA），我们能够研究[细菌名称]的整个蛋白质组，旨在开发一种疫苗。基于该分析，20370种蛋白质被鉴定为核心蛋白质，这些蛋白质进一步用于根据几个疫苗候选参数鉴定潜在的疫苗靶点。针对该细菌的优先疫苗靶点是：1型菌毛蛋白、鞭毛钩长度控制蛋白（FliK）、鞭毛钩相关蛋白（FlgK）、卷曲菌毛产生组装/转运蛋白（CsgF）、菌毛/菌毛外膜引入蛋白、菌毛/菌毛外膜引入蛋白、分子伴侣、鞭毛丝帽蛋白（FliD）、依赖TonB的血红蛋白/转铁蛋白/乳铁蛋白家族受体、孔蛋白（OmpA）、鞭毛基体杆蛋白（FlgF）和鞭毛钩-基体复合体蛋白（FliE）。在表位预测阶段，针对上述蛋白质预测了不同的抗原性表位、免疫原性表位、非致敏性表位和非毒性表位。将所选表位组合以生成多表位疫苗构建体，并添加霍乱毒素B亚基（佐剂）以增强疫苗的抗原性。使用疫苗三维模型对疫苗进行了向下分析。对接研究证实，该疫苗与MHC-I、MHC-II和TLR-4免疫细胞受体强烈结合。此外，分子动力学模拟证实，疫苗表位暴露于自然环境和宿主免疫系统，并解释了疫苗与受体之间强烈的分子间结合。基于研究结果，模型疫苗构建体似乎有能力在宿主体内产生保护性免疫反应，使其成为进一步体外和体内研究的有吸引力的候选对象。
