Kafle Alok, Ojha Suvash Chandra
Department of Tropical Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
WHO Collaborating Centre for Research and Control of Opisthorchiasis, Khon Kaen University, Khon Kaen, Thailand.
Front Pharmacol. 2024 Jul 15;15:1410453. doi: 10.3389/fphar.2024.1410453. eCollection 2024.
The liver fluke (), a neglected tropical disease (NTD), endemic to the Great Mekong Subregion (GMS), mainly afflicts the northeastern region of Thailand. It is a leading cause of cholangiocarcinoma (CCA) in humans. Presently, the treatment modalities for opisthorchiasis incorporate the use of the antihelminthic drug praziquantel, the rapid occurrence of reinfection, and the looming threat of drug resistance highlight the urgent need for vaccine development. Recent advances in "omics" technologies have proven to be a powerful tool for such studies. Utilizing candidate proteins identified through proteomics and refined immunoproteomics, reverse vaccinology (RV) offers promising prospects for designing vaccines targeting essential antibody responses to eliminate parasite. Machine learning-based computational tools can predict epitopes of candidate protein/antigens exhibiting high binding affinities for B cells, MHC classes I and II, indicating strong potential for triggering both humoral and cell-mediated immune responses. Subsequently, these vaccine designs can undergo population-specific testing and docking/dynamics studies to assess efficacy and synergistic immunogenicity. Hence, refining proteomics data through immunoinformatics and employing computational tools to generate antigen-specific targets for trials offers a targeted and efficient approach to vaccine development that applies to all domains of parasite infections. In this review, we delve into the strategic antigen selection process using omics modalities for the parasite and propose an innovative framework for vaccine design. We harness omics technologies to revolutionize vaccine development, promising accelerated discoveries and streamlined preclinical and clinical evaluations.
肝吸虫病是一种被忽视的热带病,在大湄公河次区域(GMS)流行,主要影响泰国东北部地区。它是人类胆管癌(CCA)的主要病因。目前,华支睾吸虫病的治疗方式包括使用抗蠕虫药物吡喹酮,但再感染的迅速发生以及耐药性的潜在威胁凸显了开发疫苗的迫切需求。“组学”技术的最新进展已被证明是此类研究的有力工具。利用通过蛋白质组学鉴定并经免疫蛋白质组学优化的候选蛋白,反向疫苗学(RV)为设计针对消除寄生虫的必需抗体反应的疫苗提供了广阔前景。基于机器学习的计算工具可以预测对B细胞、I类和II类主要组织相容性复合体(MHC)具有高结合亲和力的候选蛋白/抗原的表位,表明其在触发体液免疫和细胞介导免疫反应方面具有强大潜力。随后,这些疫苗设计可进行针对特定人群的测试以及对接/动力学研究,以评估疗效和协同免疫原性。因此,通过免疫信息学优化蛋白质组学数据并利用计算工具生成用于试验的抗原特异性靶点,为疫苗开发提供了一种有针对性且高效的方法,适用于寄生虫感染的所有领域。在本综述中,我们深入探讨了使用组学方法对该寄生虫进行战略抗原选择的过程,并提出了一种创新的疫苗设计框架。我们利用组学技术彻底改变疫苗开发,有望加速发现并简化临床前和临床评估。