Department of Biosciences, COMSATS University Islamabad (CUI), Islamabad, Pakistan.
Department of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada.
PLoS One. 2023 Dec 14;18(12):e0294663. doi: 10.1371/journal.pone.0294663. eCollection 2023.
Hepatitis E virus (HEV) is one of the leading acute liver infections triggered by viral hepatitis. Patients infected with HEV usually recover and the annual death rate is negligible. Currently, there is no HEV licensed vaccine available globally. This study was carried out to design a multi-epitope HEV peptide-based vaccine by retrieving already experimentally validated epitopes from ViPR database leading to epitope prioritization. Epitopes selected as potential vaccine candidates were non-allergen, immunogenic, soluble, non-toxic and IFN gamma positive. The epitopes were linked together by AAY linkers and the linker EAAAK was used to join adjuvant with epitopes. Toll-like receptor (TLR)-4 agonist was used as an adjuvant to boost efficacy of the vaccine. Furthermore, codon optimization followed by disulfide engineering was performed to analyse the designed vaccine's structural stability. Computational modeling of the immune simulation was done to examine the immune response against the vaccine. The designed vaccine construct was docked with TLR-3 receptor for their interactions and then subjected to molecular dynamic simulations. The vaccine model was examined computationally towards the capability of inducing immune responses which showed the induction of both humoral and cell mediated immunity. Taken together, our study suggests an In-silico designed HEV based multi-epitope peptide-based vaccine (MEPV) that needs to be examined in the wet lab-based data that can help to develop a potential vaccine against HEV.
戊型肝炎病毒(HEV)是由病毒性肝炎引起的主要急性肝脏感染之一。感染 HEV 的患者通常会康复,且年死亡率可忽略不计。目前,全球尚无获得许可的 HEV 疫苗。本研究旨在通过从 ViPR 数据库中检索已通过实验验证的表位来设计基于多表位 HEV 肽的疫苗,从而进行表位优先级排序。选择作为潜在疫苗候选物的表位是非过敏原、免疫原性、可溶、无毒和 IFN 伽马阳性的。这些表位通过 AAY 接头连接在一起,并用 EAAAK 接头将佐剂与表位连接起来。使用 Toll 样受体(TLR)-4 激动剂作为佐剂来提高疫苗的功效。此外,还进行了密码子优化和二硫键工程分析,以分析设计疫苗的结构稳定性。进行免疫模拟的计算建模以检查针对疫苗的免疫反应。设计的疫苗结构与 TLR-3 受体对接以研究它们的相互作用,然后进行分子动力学模拟。对疫苗模型进行了计算检查,以评估其诱导免疫反应的能力,结果表明其可诱导体液和细胞介导的免疫。综上所述,我们的研究提出了一种基于计算机设计的 HEV 多表位肽疫苗(MEPV),需要在基于湿实验室的数据中进行检验,这有助于开发针对 HEV 的潜在疫苗。