Bioinformatics Centre, Savitribai Phule Pune University, Pune 411007, India.
Department of Biotechnology, Savitribai Phule Pune University, Pune 411007, India; Department of Microbial Genome Research, Leibniz Institute DSMZ - German Collection of Microorganisms and Cell Cultures, Braunschweig 38124, Germany; Institute of Microbiology, Technical University of Braunschweig, Braunschweig 38106, Germany.
Vaccine. 2024 Oct 24;42(24):126106. doi: 10.1016/j.vaccine.2024.07.007. Epub 2024 Jul 8.
The development of effective vaccines against Hepatitis C Virus (HCV) remains a global health priority and challenge. In this study, we employed an integrative approach combining computational epitope prediction with experimental validation to identify immunogenic peptides targeting the E1 glycoprotein of HCV. In the present report, computational data from various epitope prediction algorithms such as IEDB and SYFPEITHI, followed by molecular dynamics (MD) simulations and immuno-informatics analysis is presented. Through computational screening, we identified potential epitope candidates, with QVRNSSGLY (P3) and QLFTFSPRH (P7) emerging as promising candidates. MD simulations revealed stable interactions between these epitopes and MHC molecule, further validated by free energy estimations using MMPBSA method. Immuno-informatics analysis supported these findings, showing high binding potential and immunogenicity scores for the selected peptides. Subsequent synthesis and characterization of epitope peptides confirmed their structural integrity and purity required for conducting immune activation assays. Experimental immunological assays carried out in this study involved epitope peptide induced activation of CD8 + and CD4 + T cells from healthy human subjects and HCV- recovered patients. Data from experimental validation revealed significant cytokine release upon exposure to epitope peptides, particularly TNF-a, IL-6, and GM-CSF, indicative of robust immune responses. Notably, peptides P3 and P7 exhibited the most pronounced cytokine induction profiles, underscoring their potential as vaccine candidates. Further investigations addressing the mechanism of action of these epitope peptides under preclinical and clinical settings may help in developing effective vaccine against HCV.
开发针对丙型肝炎病毒 (HCV) 的有效疫苗仍然是全球卫生的重点和挑战。在这项研究中，我们采用了一种综合方法，将计算表位预测与实验验证相结合，以鉴定针对 HCV E1 糖蛋白的免疫原性肽。在本报告中，展示了来自各种表位预测算法（如 IEDB 和 SYFPEITHI）的计算数据，随后进行了分子动力学 (MD) 模拟和免疫信息学分析。通过计算筛选，我们确定了潜在的表位候选物，其中 QVRNSSGLY（P3）和 QLFTFSPRH（P7）是有前途的候选物。MD 模拟揭示了这些表位与 MHC 分子之间的稳定相互作用，通过 MMPBSA 方法进行自由能估计进一步验证了这一点。免疫信息学分析支持了这些发现，表明所选肽具有高结合潜力和免疫原性评分。随后合成和表征表位肽证实了它们具有进行免疫激活测定所需的结构完整性和纯度。本研究进行的实验免疫学测定涉及来自健康人类受试者和 HCV 康复患者的 CD8+和 CD4+T 细胞对表位肽的诱导激活。实验验证的数据显示，暴露于表位肽后会释放出显著的细胞因子，特别是 TNF-a、IL-6 和 GM-CSF，表明存在强烈的免疫反应。值得注意的是，肽 P3 和 P7 表现出最显著的细胞因子诱导谱，强调了它们作为疫苗候选物的潜力。进一步的研究，针对这些表位肽在临床前和临床环境中的作用机制，可能有助于开发针对 HCV 的有效疫苗。
