Khalid Hina, Ashfaq Usman Ali
Department of Bioinformatics and Biotechnology, Government College University, Faisalabad, Pakistan.
Department of Bioinformatics and Biotechnology, Government College University, Faisalabad, Pakistan.
J Biomed Inform. 2020 Aug;108:103498. doi: 10.1016/j.jbi.2020.103498. Epub 2020 Jul 1.
Hepatitis C Virus (HCV) infection is a major cause of chronic liver disease, hepatocellular carcinoma, and the single most common indication for liver transplantation. HCV vaccines eliciting specific T-cell responses, have been considered as potent method to prevent HCV infection. Despite several reports on progress of vaccine, these vaccine failed in mediating clinical relevance activity against HCV in humans. In this study we integrated both immunoinformatic and molecular docking approach to present a multiepitope vaccine against HCV by designating 17 conserved epitopes from eight viral proteins such as Core protein, E1, E2, NS2, NS34A, NS4B, NS5A, and NS5B. The epitopes were prioritized based on conservation among epitopes of T cell, B cell and IFN-γ that were then scanned for non-homologous to host and antigenicity. The prioritized epitopes were then linked together by AAY linker and adjuvant (β-defensin) were attached at N-terminal to enhance immunogenic potential. The construct thus formed were subjected to structural modeling and physiochemical characteristics. The modeled structure were successfully docked to antigenic receptor TLR-3 and In-silico cloning confers the authenticity of its expression efficiency. However, the proposed construct need to be validate experimentally to ensure its safety and immunogenic profile.
丙型肝炎病毒(HCV)感染是慢性肝病、肝细胞癌的主要病因,也是肝移植最常见的单一指征。引发特异性T细胞反应的HCV疫苗,被认为是预防HCV感染的有效方法。尽管有几篇关于疫苗进展的报道,但这些疫苗在介导针对人类HCV的临床相关活性方面均告失败。在本研究中,我们整合了免疫信息学和分子对接方法,通过从核心蛋白、E1、E2、NS2、NS3/4A、NS4B、NS5A和NS5B等八种病毒蛋白中指定17个保守表位,设计了一种针对HCV的多表位疫苗。这些表位根据T细胞、B细胞和IFN-γ表位之间的保守性进行优先级排序,然后扫描其与宿主的非同源性和抗原性。然后通过AAY接头将优先级表位连接在一起,并在N端连接佐剂(β-防御素)以增强免疫原性潜力。对由此形成的构建体进行结构建模和理化特性分析。将建模结构成功对接至抗原受体TLR-3,并且电子克隆赋予其表达效率的真实性。然而,所提出的构建体需要通过实验验证,以确保其安全性和免疫原性特征。