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运用免疫信息学技术针对丙型肝炎病毒感染的多表位疫苗的计算机辅助设计

Computational design of multi-epitope vaccine against Hepatitis C Virus infection using immunoinformatics techniques.

作者信息

Zubair Sara, Parvaiz Fahed, Abualait Turki, Al-Regaiey Khalid, Anwar Tasneem, Zafar Mahnoor, Kaleem Imdad, Bashir Shahid

机构信息

Department of Biosciences, COMSATS University Islamabad (CUI), Islamabad, Pakistan.

College of Applied Medical Sciences, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.

出版信息

PLoS One. 2025 Jan 24;20(1):e0317520. doi: 10.1371/journal.pone.0317520. eCollection 2025.

DOI:10.1371/journal.pone.0317520
PMID:39854342
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11759374/
Abstract

Hepatitis C Virus (HCV) is a blood borne pathogen that affects around 200 million individuals worldwide. Immunizations against the Hepatitis C Virus are intended to enhance T-cell responses and have been identified as a crucial component of successful antiviral therapy. Nevertheless, attempts to mediate clinically relevant anti-HCV activity in people have mainly failed, despite the vaccines present satisfactory progress. In this study, we used an array of immunoinformatics approaches to design a multiepitope peptide-based vaccine against HCV by emphasizing 6 conserved epitopes from viral protein NS5B. The potential epitopes were examined for their possible antigenic combination with each other along with GPGPG linkers using structural modeling and epitope-epitope interaction analysis. An adjuvant (β-defensin) was introduced to the N-terminus to increase the immunogenicity of the vaccine construct. Molecular dynamics simulation discloses the most stable structure of the proposed vaccine. The designed vaccine is potentially antigenic in nature and can form stable and significant interaction with both receptors TLR2 and TLR3. The vaccine construct was also subjected to In-Silico cloning which confirmed its expression efficiency in a vector. The findings indicate that the designed multi-epitope vaccine have a great potential for preclinical and clinical research, which is an important step in addressing the problems related to HCV infection.

摘要

丙型肝炎病毒(HCV)是一种血源性病原体,全球约有2亿人受其影响。针对丙型肝炎病毒的免疫接种旨在增强T细胞反应,并且已被确定为成功抗病毒治疗的关键组成部分。然而,尽管疫苗取得了令人满意的进展,但在人体中介导具有临床相关性的抗HCV活性的尝试大多失败了。在本研究中,我们使用了一系列免疫信息学方法,通过强调病毒蛋白NS5B的6个保守表位,设计了一种基于多表位肽的抗HCV疫苗。使用结构建模和表位-表位相互作用分析,研究了潜在表位彼此之间以及与GPGPG接头可能的抗原组合。在N端引入佐剂(β-防御素)以提高疫苗构建体的免疫原性。分子动力学模拟揭示了所提出疫苗的最稳定结构。所设计的疫苗本质上具有潜在抗原性,并且可以与受体TLR2和TLR3形成稳定且显著的相互作用。疫苗构建体还进行了电子克隆,证实了其在载体中的表达效率。研究结果表明,所设计的多表位疫苗在临床前和临床研究中具有巨大潜力,这是解决与HCV感染相关问题的重要一步。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/325e/11759374/2732143b5dec/pone.0317520.g014.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/325e/11759374/6721c7ca58f3/pone.0317520.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/325e/11759374/772656cca69d/pone.0317520.g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/325e/11759374/82e479299708/pone.0317520.g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/325e/11759374/c3c50de4afef/pone.0317520.g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/325e/11759374/21ad4112eb35/pone.0317520.g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/325e/11759374/70b676fe2f78/pone.0317520.g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/325e/11759374/2732143b5dec/pone.0317520.g014.jpg

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