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运用反向疫苗学和泛基因组免疫信息学开发一种针对山羊痘病毒的潜在疫苗。

Development of a potential vaccine against Capripox virus implementing reverse vaccinology and pan-genomic immunoinformatics.

作者信息

Tareq Md Mohaimenul Islam, Biswas Sattyajit, Rahman Farazi Abinash, Siam Labib Sharirar, Tauhida Sadia Jannat, Ahmed Shamim, Shovon Hasan Jafre, Ahmed Mariya, Jerin Kazi Afrin, Hasan Md Nazmul

机构信息

Laboratory of Pharmaceutical Biotechnology and Bioinformatics, Department of Genetic Engineering and Biotechnology, Jashore University of Science and Technology, Jashore, Bangladesh.

Department of Genetic Engineering and Biotechnology, Jashore University of Science and Technology, Jashore, Bangladesh.

出版信息

PLoS One. 2025 Jul 2;20(7):e0326310. doi: 10.1371/journal.pone.0326310. eCollection 2025.

Abstract

CPXV is responsible for animal diseases affecting cattle (Lumpy Skin Disease), sheep (Sheeppox), and goats (Goatpox). During outbreaks, these diseases have huge socio-economic effects. Now, no vaccination that is effective against sheeppox, goatpox, and lumpy skin disease is available. This work used an immunoinformatic methodology to discover possible targets for vaccination against CPXV. After the 122 CPXV proteins were obtained from the Vipr database, several investigations into the proteins' virulence, antigenicity, toxicity, solubility, and IFN-g activity were carried out. Three outer membrane and extracellular proteins were selected to predict their B-cell and T-cell epitopes based on certain distinctive features. These epitopes exhibit conservation across three species, namely Sheeppox virus (SPPV), Goatpox virus (GTPV), and Lumpy skin disease virus (LSDV) of CPXV. This will provide more comprehensive immunity against diverse virus strains worldwide. Nine MHC-I, MHC-II, and B-cell epitopes were selected to generate multi-epitope vaccine constructions. These constructs were linked using AAY, GPGPG, and KK linkers and 50S ribosomal protein L7/L12 adjuvants to enhance the immunogenicity of the vaccines. Molecular modeling and structural validation enabled the production of vaccine constructs with high-quality 3D structures. CPXV (Protein A35, Protein Resolve A22, and Scaffold Protein) was selected for further analysis because of its varied immunological and physiochemical properties (Number of Amino Acids, Molecular Weight (Daltons), Theoretical pI Aliphatic index, Grand average of hydropathicity (GRAVY), Instability index GC content, and CAI value) and docking scores. The bacterial expression system showed notable gene expression for the CPXV-V5 vaccine, as shown by computational cloning analysis. Molecular dynamics (MD) simulations revealed structural stability and long-term epitope visibility, implying strong immune responses after delivery. These results suggest that the developed vaccines might be quite safe and effective in practical settings, and they offer a solid foundation for further experimental verification.

摘要

痘苗病毒(CPXV)可引发影响牛的疾病(牛结节性皮肤病)、羊的疾病(羊痘)以及山羊的疾病(山羊痘)。在疫情爆发期间,这些疾病会产生巨大的社会经济影响。目前,尚无有效预防羊痘、山羊痘和牛结节性皮肤病的疫苗。这项研究采用免疫信息学方法来探寻针对CPXV的潜在疫苗靶点。从Vipr数据库获取122种CPXV蛋白后,对这些蛋白的毒力、抗原性、毒性、溶解性和干扰素-γ活性展开了多项研究。基于某些独特特征,挑选出三种外膜和细胞外蛋白来预测其B细胞和T细胞表位。这些表位在痘苗病毒的三种病毒,即羊痘病毒(SPPV)、山羊痘病毒(GTPV)和牛结节性皮肤病病毒(LSDV)中具有保守性。这将为全球范围内抵御多种病毒株提供更全面的免疫力。挑选出九个主要组织相容性复合体I类(MHC-I)、II类(MHC-II)和B细胞表位,构建多表位疫苗结构。这些结构通过AAY、GPGPG和KK连接子以及50S核糖体蛋白L7/L12佐剂相连,以增强疫苗的免疫原性。分子建模和结构验证使得能够生产出具有高质量三维结构的疫苗构建体。由于痘苗病毒(蛋白A35、蛋白溶解A22和支架蛋白)具有多样的免疫和物理化学特性(氨基酸数量、分子量(道尔顿)、理论等电点、脂肪族指数、亲水性总平均值(GRAVY)、不稳定指数、GC含量和密码子适应指数(CAI)值)以及对接分数,因此被选作进一步分析对象。计算克隆分析表明,细菌表达系统对CPXV-V5疫苗显示出显著的基因表达。分子动力学(MD)模拟揭示了结构稳定性和长期表位可见性,这意味着疫苗接种后会产生强烈的免疫反应。这些结果表明,所研发的疫苗在实际应用中可能相当安全有效,为进一步的实验验证奠定了坚实基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbe5/12221009/aedbfa699298/pone.0326310.g001.jpg

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