School of Advanced Technologies in Medicine, Fasa University of Medical Sciences, Fasa, Iran.
Department of Medical Laboratory Techniques, Faculty of Health and Medical Techniques, Imam Ja'afar Al-Sadiq University, Al Muthanna, Iraq.
PLoS One. 2022 Aug 30;17(8):e0272582. doi: 10.1371/journal.pone.0272582. eCollection 2022.
Hepatitis C virus (HCV) infects the liver and causes chronic infection. Several mutations in the viral genome have been associated with drug resistance development. Currently, there is no approved vaccine against the HCV. The employment of computational biology is the primary and crucial step for vaccine design or antiviral therapy which can substantially reduce the duration and cost of studies. Therefore, in this study, we designed a multi-epitope vaccine using various immunoinformatics tools to elicit the efficient human immune responses against the HCV. Initially, various potential (antigenic, immunogenic, non-toxic and non-allergenic) epitope segments were extracted from viral structural and non-structural protein sequences using multiple screening methods. The selected epitopes were linked to each other properly. Then, toll-like receptors (TLRs) 3 and 4 agonists (50S ribosomal protein L7/L12 and human β-defensin 2, respectively) were added to the N-terminus of the final vaccine sequence to increase its immunogenicity. The 3D structure of the vaccine was modeled. Molecular dynamics simulations studies verified the high stability of final free vaccines and in complex with TLR3 and TLR4. These constructs were also antigenic, non-allergenic, nontoxic and immunogenic. Although the designed vaccine traits were promising as a potential candidate against the HCV infection, experimental studies and clinical trials are required to verify the protective traits and safety of the designed vaccine.
丙型肝炎病毒(HCV)感染肝脏并引起慢性感染。病毒基因组中的几个突变与耐药性的发展有关。目前,还没有针对 HCV 的批准疫苗。计算生物学的应用是疫苗设计或抗病毒治疗的首要和关键步骤,这可以大大缩短研究的时间和成本。因此,在这项研究中,我们使用各种免疫信息学工具设计了一种多表位疫苗,以引发针对 HCV 的有效人体免疫反应。最初,使用多种筛选方法从病毒结构和非结构蛋白序列中提取各种潜在的(抗原性、免疫原性、无毒和无变应原性)表位片段。选择的表位被适当地连接在一起。然后,将 Toll 样受体(TLR)3 和 4 激动剂(分别为 50S 核糖体蛋白 L7/L12 和人β防御素 2)添加到最终疫苗序列的 N 端,以提高其免疫原性。对疫苗的 3D 结构进行了建模。分子动力学模拟研究验证了最终游离疫苗及其与 TLR3 和 TLR4 复合物的高稳定性。这些构建体也是抗原性的、无变应原性的、无毒的和免疫原性的。尽管设计的疫苗特性作为 HCV 感染的潜在候选物具有很大的希望,但需要进行实验研究和临床试验来验证设计疫苗的保护特性和安全性。