{"title":"In Silico Driven Multi-Epitope Subunit Candidate Vaccine against Bovine Tuberculosis","authors":"Md. Atik Faysal, Fatema Yeasmin Tanni, Md. Mahfujur Rahman, Md Anisur Rahman, Md. Shahidur Rahman Chowdhury, Ho-Seong Cho, Md. Mukter Hossain, Md Bashir Uddin","doi":"10.1155/2024/5534041","DOIUrl":null,"url":null,"abstract":"<div>\n <p>Bovine tuberculosis (bTB), caused by <i>Mycobacterium bovis</i>, poses significant zoonotic and economic challenges globally. The current prevention and treatment options are limited and increasingly complicated by the emergence of multidrug-resistant strains. This study employs reverse vaccinology and immunoinformatics to design a multi-epitope subunit vaccine targeting the MPB83, ArfA, DnaK, GrpE, and LpqH proteins of <i>M. bovis</i>. The T-cell and B-cell epitopes of the candidate vaccine were predicted and evaluated for antigenicity, allergenicity, and toxicity. The promising epitopes were then assembled into three vaccine constructs (bTBV1, bTBV2, and bTBV3) using appropriate adjuvants, pan HLA DR-binding epitope (PADRE), and linkers. The constructs were analyzed for physicochemical properties, 3D structure, cytokines induction and stability, followed by molecular docking with bovine CD molecules and toll-like receptor, TLR-9. Among the candidates, bTBV3 was chosen as one of the most promising vaccine candidates due to its high aliphatic index (67.60), lowest instability score (27.26), and a strong binding affinity. Molecular dynamics simulations and the results of interactions between the vaccine–receptor complexes (eigenvalue 2.318704e-06) show that the vaccine construct bTBV3 is stable. <i>In silico</i> immune simulation findings, such as elevated IgM levels and increased Th cell populations, suggest that the designed multi-epitope vaccine candidate bTBV3 elicits robust humoral and cellular immune responses, confirming the vaccine’s potential efficacy. Additionally, codon optimization (CAI: 0.997 and GC: 54.687%) and <i>in silico</i> cloning facilitated efficient expression in <i>E. coli</i>. This study highlights the potential of bioinformatics-driven approaches in developing effective subunit vaccines against bTB, providing a foundation for experimental validation and future applications in combating this pervasive zoonotic disease, bovine tuberculosis.</p>\n </div>","PeriodicalId":234,"journal":{"name":"Transboundary and Emerging Diseases","volume":"2024 1","pages":""},"PeriodicalIF":3.5000,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/5534041","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Transboundary and Emerging Diseases","FirstCategoryId":"97","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1155/2024/5534041","RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
引用次数: 0
Abstract
Bovine tuberculosis (bTB), caused by Mycobacterium bovis, poses significant zoonotic and economic challenges globally. The current prevention and treatment options are limited and increasingly complicated by the emergence of multidrug-resistant strains. This study employs reverse vaccinology and immunoinformatics to design a multi-epitope subunit vaccine targeting the MPB83, ArfA, DnaK, GrpE, and LpqH proteins of M. bovis. The T-cell and B-cell epitopes of the candidate vaccine were predicted and evaluated for antigenicity, allergenicity, and toxicity. The promising epitopes were then assembled into three vaccine constructs (bTBV1, bTBV2, and bTBV3) using appropriate adjuvants, pan HLA DR-binding epitope (PADRE), and linkers. The constructs were analyzed for physicochemical properties, 3D structure, cytokines induction and stability, followed by molecular docking with bovine CD molecules and toll-like receptor, TLR-9. Among the candidates, bTBV3 was chosen as one of the most promising vaccine candidates due to its high aliphatic index (67.60), lowest instability score (27.26), and a strong binding affinity. Molecular dynamics simulations and the results of interactions between the vaccine–receptor complexes (eigenvalue 2.318704e-06) show that the vaccine construct bTBV3 is stable. In silico immune simulation findings, such as elevated IgM levels and increased Th cell populations, suggest that the designed multi-epitope vaccine candidate bTBV3 elicits robust humoral and cellular immune responses, confirming the vaccine’s potential efficacy. Additionally, codon optimization (CAI: 0.997 and GC: 54.687%) and in silico cloning facilitated efficient expression in E. coli. This study highlights the potential of bioinformatics-driven approaches in developing effective subunit vaccines against bTB, providing a foundation for experimental validation and future applications in combating this pervasive zoonotic disease, bovine tuberculosis.
期刊介绍:
Transboundary and Emerging Diseases brings together in one place the latest research on infectious diseases considered to hold the greatest economic threat to animals and humans worldwide. The journal provides a venue for global research on their diagnosis, prevention and management, and for papers on public health, pathogenesis, epidemiology, statistical modeling, diagnostics, biosecurity issues, genomics, vaccine development and rapid communication of new outbreaks. Papers should include timely research approaches using state-of-the-art technologies. The editors encourage papers adopting a science-based approach on socio-economic and environmental factors influencing the management of the bio-security threat posed by these diseases, including risk analysis and disease spread modeling. Preference will be given to communications focusing on novel science-based approaches to controlling transboundary and emerging diseases. The following topics are generally considered out-of-scope, but decisions are made on a case-by-case basis (for example, studies on cryptic wildlife populations, and those on potential species extinctions):
Pathogen discovery: a common pathogen newly recognised in a specific country, or a new pathogen or genetic sequence for which there is little context about — or insights regarding — its emergence or spread.
Prevalence estimation surveys and risk factor studies based on survey (rather than longitudinal) methodology, except when such studies are unique. Surveys of knowledge, attitudes and practices are within scope.
Diagnostic test development if not accompanied by robust sensitivity and specificity estimation from field studies.
Studies focused only on laboratory methods in which relevance to disease emergence and spread is not obvious or can not be inferred (“pure research” type studies).
Narrative literature reviews which do not generate new knowledge. Systematic and scoping reviews, and meta-analyses are within scope.