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针对多种不同人类乳头瘤病毒类型的新型广谱多表位疫苗的设计及免疫分子分析

Designing and immunomolecular analysis of a new broad-spectrum multiepitope vaccine against divergent human papillomavirus types.

作者信息

Ehsasatvatan Maryam, Baghban Kohnehrouz Bahram

机构信息

Department of Plant Breeding & Biotechnology, Faculty of Agriculture, University of Tabriz, Tabriz, Iran.

出版信息

PLoS One. 2024 Dec 2;19(12):e0311351. doi: 10.1371/journal.pone.0311351. eCollection 2024.

Abstract

Human papillomavirus (HPV), which is transmitted through sexual activity, is the primary cause of cervical cancer and the fourth most common type of cancer in women. In this study, an immunoinformatics approach was employed to predict immunodominant epitopes from a diverse array of antigens with the ultimate objective of designing a potent multiepitope vaccine against multiple HPV types. Immunodominant B cell, cytotoxic T cell (CTL), and helper T cell (HTL) epitopes were predicted using bioinformatics tools These epitopes were subsequently analyzed using various immunoinformatics tools, and those that exhibited high antigenicity, immunogenicity, non-allergenicity, non-toxicity, and excellent conservation were selected. The selected epitopes were linked with appropriate linkers and adjuvants to formulate a broad-spectrum multiepitope vaccine candidate against HPV. The stability of the multiepitope vaccine candidate was confirmed through structural analysis, and docking results indicated a high affinity for Toll-like receptors (TLR2 and TLR4). Molecular dynamics simulations demonstrated a persistent interaction of TLR2 and TLR4 with the multiepitope vaccine candidate. In silico immunological simulations showed that three injections of the multiepitope vaccine candidate resulted in high levels of B- and T-cell immune responses. Moreover, the in silico cloning results indicated that the multiepitope vaccine candidate could be expressed in substantial amounts in E. coli. The results of this study imply that designing a broad-spectrum vaccine against various HPV types using computational methods is plausible; however, experimental validation and safety testing to confirm the findings is essential.

摘要

人乳头瘤病毒(HPV)通过性活动传播,是宫颈癌的主要病因,也是女性中第四常见的癌症类型。在本研究中,采用免疫信息学方法从多种抗原中预测免疫显性表位,最终目的是设计一种针对多种HPV类型的高效多表位疫苗。使用生物信息学工具预测免疫显性B细胞、细胞毒性T细胞(CTL)和辅助性T细胞(HTL)表位。随后使用各种免疫信息学工具对这些表位进行分析,选择那些具有高抗原性、免疫原性、无致敏性、无毒性且具有良好保守性的表位。将所选表位与合适的连接子和佐剂连接,以制备一种针对HPV的广谱多表位疫苗候选物。通过结构分析证实了多表位疫苗候选物的稳定性,对接结果表明其与Toll样受体(TLR2和TLR4)具有高亲和力。分子动力学模拟表明TLR2和TLR4与多表位疫苗候选物持续相互作用。计算机免疫模拟显示,三次注射多表位疫苗候选物可导致高水平的B细胞和T细胞免疫反应。此外,计算机克隆结果表明,多表位疫苗候选物可在大肠杆菌中大量表达。本研究结果表明,使用计算方法设计针对多种HPV类型的广谱疫苗是可行的;然而,进行实验验证和安全性测试以证实这些发现至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7938/11611089/473b84046aed/pone.0311351.g001.jpg

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