Department of Biochemistry, Bahauddin Zakariya University, Multan, Pakistan.
Department of Bioinformatics, Kohsar University Murree, Murree, Pakistan.
Front Immunol. 2024 Jul 10;15:1281544. doi: 10.3389/fimmu.2024.1281544. eCollection 2024.
is the etiological agent of the disease opisthorchiasis and related cholangiocarcinoma (CCA). It infects fish-eating mammals and more than 10 million people in Southeast Asia suffered from opisthorchiasis with a high fatality rate. The only effective drug against this parasite is Praziquantel, which has significant side effects. Due to the lack of appropriate treatment options and the high death rate, there is a dire need to develop novel therapies against this pathogen. In this study, we designed a multi-epitope chimeric vaccine design against by using immunoinformatics approaches. Non-allergenic and immunogenic MHC-1, MHC-2, and B cell epitopes of three candidate proteins thioredoxin peroxidase (), cathepsin F1 () and calreticulin () of , were predicted to construct a potent multiepitope vaccine. The coverage of the HLA-alleles of these selected epitopes was determined globally. Four vaccine constructs made by different adjuvants and linkers were evaluated in the context of their physicochemical properties, antigenicity, and allergenicity. Protein-protein docking and MD simulation found that vaccines 3 was more stable and had a higher binding affinity for TLR2 and TLR4 immune receptors. restriction cloning of vaccine model led to the formation of plasmid constructs for expression in a suitable host. Finally, the immune simulation showed strong immunological reactions to the engineered vaccine. These findings suggest that the final vaccine construct has the potential to be validated by and experiments to confirm its efficacy against the CCA causing .
是肝吸虫病及相关胆管癌(CCA)的病原体。它感染食鱼哺乳动物,东南亚有超过 1000 万人感染肝吸虫病,死亡率很高。唯一有效的抗寄生虫药物是吡喹酮,但它有明显的副作用。由于缺乏适当的治疗选择和高死亡率,迫切需要开发针对这种病原体的新疗法。在这项研究中,我们使用免疫信息学方法设计了针对 的多表位嵌合疫苗。预测三种候选蛋白(硫氧还蛋白过氧化物酶()、组织蛋白酶 F1()和钙网蛋白())的非变应原性和免疫原性 MHC-1、MHC-2 和 B 细胞表位,以构建一种有效的多表位疫苗。这些选定表位的 HLA 等位基因的覆盖率在全球范围内确定。评估了由不同佐剂和接头制成的四种疫苗构建体,以评估其物理化学性质、抗原性和变应原性。蛋白质-蛋白质对接和 MD 模拟发现,疫苗 3 更稳定,与 TLR2 和 TLR4 免疫受体的结合亲和力更高。疫苗模型的限制性克隆导致在合适的宿主中表达的质粒构建体的形成。最后,免疫模拟显示对工程疫苗有强烈的免疫反应。这些发现表明,最终的疫苗构建体有可能通过 和 实验来验证其对导致 CCA 的 的疗效。