Ashgar Sami S, Faidah Hani, Bantun Farkad, Jalal Naif A, Qusty Naeem F, Darwish Abdulla, Haque Shafiul, Janahi Essam M
Department of Microbiology, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia.
Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia.
Front Mol Biosci. 2023 Jul 25;10:1212119. doi: 10.3389/fmolb.2023.1212119. eCollection 2023.
is one of the major precarious pathogens accountable for over 1.2 million fatalities annually. The key drivers for pneumococcal vaccine development involve high morbidity and mortality in over one million cases, especially in very young children and the elderly. In this study, immunoinformatics was integrated with subtractive proteomics to find antigenic proteins for designing a multi-epitope vaccine against . As prospective vaccine targets, the developed pipeline identified two antigenic proteins, i.e., penicillin-binding protein and ATP synthase subunit. Several immunoinformatics and bioinformatics resources were used to forecast T- and B-cell epitopes from specific proteins. By employing a mixture of five cytotoxic T-cell lymphocytes, six helper T-cell lymphocytes, and seven linear B-cell lymphocyte epitopes, a 392 amino acid-long vaccine was designed. To enhance immune responses, the designed vaccine was coupled with a cholera enterotoxin subunit B adjuvant. The designed vaccine was highly antigenic, non-allergenic, and stable for human usage. The stability of the vaccine with toll-like receptor-4 was evaluated by molecular docking and molecular dynamic simulation. In addition, immunological simulation was performed to test its real-world potency. The vaccine codon was then cloned . Overall, this study paves the way for the development of a multi-epitope vaccine under laboratory conditions. Furthermore, the current findings warrant for the experimental validation of the final multi-epitope vaccine construct to demonstrate its immunological reinforcing capability and clinical applicability.
是每年导致超过120万人死亡的主要危险病原体之一。肺炎球菌疫苗研发的主要驱动因素包括在超过100万病例中出现的高发病率和高死亡率,尤其是在幼儿和老年人中。在本研究中,免疫信息学与消减蛋白质组学相结合,以寻找用于设计针对[病原体名称未明确]的多表位疫苗的抗原蛋白。作为潜在的疫苗靶点,所开发的流程确定了两种抗原蛋白,即青霉素结合蛋白和ATP合酶亚基。利用多种免疫信息学和生物信息学资源来预测特定蛋白质的T细胞和B细胞表位。通过混合五种细胞毒性T淋巴细胞、六种辅助性T淋巴细胞和七种线性B淋巴细胞表位,设计了一种长度为392个氨基酸的疫苗。为增强免疫反应,将设计的疫苗与霍乱肠毒素亚基B佐剂偶联。设计的疫苗具有高度抗原性、无致敏性且对人体使用稳定。通过分子对接和分子动力学模拟评估了该疫苗与Toll样受体-4的稳定性。此外,进行了免疫模拟以测试其实际效力。然后克隆了疫苗密码子。总体而言,本研究为在实验室条件下开发多表位疫苗铺平了道路。此外,目前的研究结果需要对最终的多表位疫苗构建体进行实验验证,以证明其免疫增强能力和临床适用性。