Novel prophylactic and therapeutic multi-epitope vaccine based on Ag85A, Ag85B, ESAT-6, and CFP-10 of Mycobacterium tuberculosis using an immunoinformatics approach

Objectives Current tuberculosis (TB) control strategies face limitations, such as low antibiotic treatment compliance and a rise in multidrug resistance. Furthermore, the lack of a safe and effective vaccine compounds these challenges. The limited efficacy of existing vaccines against TB underscores...

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Main Authors: Muhammad Fikri Nugraha, Daniel Alexander Changestu, Rizky Ramadhan, Tasya Salsabila, Arsila Nurizati, Sari Eka Pratiwi, Ysrafil Ysrafil
Format: Article
Language:English
Published: Korea Disease Control and Prevention Agency 2024-08-01
Series:Osong Public Health and Research Perspectives
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Online Access:http://ophrp.org/upload/pdf/j-phrp-2024-0026.pdf
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author Muhammad Fikri Nugraha
Daniel Alexander Changestu
Rizky Ramadhan
Tasya Salsabila
Arsila Nurizati
Sari Eka Pratiwi
Ysrafil Ysrafil
author_facet Muhammad Fikri Nugraha
Daniel Alexander Changestu
Rizky Ramadhan
Tasya Salsabila
Arsila Nurizati
Sari Eka Pratiwi
Ysrafil Ysrafil
author_sort Muhammad Fikri Nugraha
collection DOAJ
description Objectives Current tuberculosis (TB) control strategies face limitations, such as low antibiotic treatment compliance and a rise in multidrug resistance. Furthermore, the lack of a safe and effective vaccine compounds these challenges. The limited efficacy of existing vaccines against TB underscores the urgency for innovative strategies, such as immunoinformatics. Consequently, this study aimed to design a targeted multi-epitope vaccine against TB infection utilizing an immunoinformatics approach. Methods The multi-epitope vaccine targeted Ag85A, Ag85B, ESAT-6, and CFP-10 proteins. The design adopted various immunoinformatics tools for cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), and linear B lymphocyte (LBL) epitope prediction, the assessment of vaccine characteristics, structure modeling, population coverage analysis, disulfide engineering, solubility prediction, molecular docking/dynamics with toll-like receptors (TLRs), codon optimization/cloning, and immune simulation. Results The multi-epitope vaccine, which was assembled using 12 CTL, 25 HTL, and 21 LBL epitopes associated with CpG adjuvants, showed promising characteristics. The immunoinformatics analysis confirmed the antigenicity, immunogenicity, and lack of allergenicity. Physicochemical evaluations indicated that the proteins were stable, thermostable, hydrophilic, and highly soluble. Docking simulations suggested high-affinity binding to TLRs, including TLR2, TLR4, and TLR9. In silico immune simulation predicted strong T cell (cytokine release) and B cell (immunoglobulin release) responses. Conclusion This immunoinformatics-designed multi-epitope vaccine targeting Ag85A, Ag85B, ESAT-6, and CFP-10 proteins showed promising characteristics in terms of stability, immunogenicity, antigenicity, solubility, and predicted induction of humoral and adaptive immune responses. This suggests its potential as a prophylactic and therapeutic vaccine against TB.
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spelling doaj-art-75a97621f1f644afa19c7b6fc37fe38c2025-08-20T02:14:44ZengKorea Disease Control and Prevention AgencyOsong Public Health and Research Perspectives2233-60522024-08-0115428630610.24171/j.phrp.2024.0026785Novel prophylactic and therapeutic multi-epitope vaccine based on Ag85A, Ag85B, ESAT-6, and CFP-10 of Mycobacterium tuberculosis using an immunoinformatics approachMuhammad Fikri Nugraha0Daniel Alexander Changestu1Rizky Ramadhan2Tasya Salsabila3Arsila Nurizati4Sari Eka Pratiwi5Ysrafil Ysrafil6 Medical Program, Faculty of Medicine, Universitas Tanjungpura, Pontianak, Indonesia Medical Program, Faculty of Medicine, Universitas Tanjungpura, Pontianak, Indonesia Medical Program, Faculty of Medicine, Universitas Tanjungpura, Pontianak, Indonesia Medical Program, Faculty of Medicine, Universitas Tanjungpura, Pontianak, Indonesia Medical Program, Faculty of Medicine, Universitas Tanjungpura, Pontianak, Indonesia Department of Biology and Pathobiology, Faculty of Medicine, Universitas Tanjungpura, Pontianak, Indonesia Department of Pharmacotherapy, Faculty of Medicine, Universitas Palangka Raya, Palangka Raya, IndonesiaObjectives Current tuberculosis (TB) control strategies face limitations, such as low antibiotic treatment compliance and a rise in multidrug resistance. Furthermore, the lack of a safe and effective vaccine compounds these challenges. The limited efficacy of existing vaccines against TB underscores the urgency for innovative strategies, such as immunoinformatics. Consequently, this study aimed to design a targeted multi-epitope vaccine against TB infection utilizing an immunoinformatics approach. Methods The multi-epitope vaccine targeted Ag85A, Ag85B, ESAT-6, and CFP-10 proteins. The design adopted various immunoinformatics tools for cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), and linear B lymphocyte (LBL) epitope prediction, the assessment of vaccine characteristics, structure modeling, population coverage analysis, disulfide engineering, solubility prediction, molecular docking/dynamics with toll-like receptors (TLRs), codon optimization/cloning, and immune simulation. Results The multi-epitope vaccine, which was assembled using 12 CTL, 25 HTL, and 21 LBL epitopes associated with CpG adjuvants, showed promising characteristics. The immunoinformatics analysis confirmed the antigenicity, immunogenicity, and lack of allergenicity. Physicochemical evaluations indicated that the proteins were stable, thermostable, hydrophilic, and highly soluble. Docking simulations suggested high-affinity binding to TLRs, including TLR2, TLR4, and TLR9. In silico immune simulation predicted strong T cell (cytokine release) and B cell (immunoglobulin release) responses. Conclusion This immunoinformatics-designed multi-epitope vaccine targeting Ag85A, Ag85B, ESAT-6, and CFP-10 proteins showed promising characteristics in terms of stability, immunogenicity, antigenicity, solubility, and predicted induction of humoral and adaptive immune responses. This suggests its potential as a prophylactic and therapeutic vaccine against TB.http://ophrp.org/upload/pdf/j-phrp-2024-0026.pdfmulti-epitope vaccineprophylaxis tuberculosis vaccinetherapeutic tuberculosis vaccine
spellingShingle Muhammad Fikri Nugraha
Daniel Alexander Changestu
Rizky Ramadhan
Tasya Salsabila
Arsila Nurizati
Sari Eka Pratiwi
Ysrafil Ysrafil
Novel prophylactic and therapeutic multi-epitope vaccine based on Ag85A, Ag85B, ESAT-6, and CFP-10 of Mycobacterium tuberculosis using an immunoinformatics approach
Osong Public Health and Research Perspectives
multi-epitope vaccine
prophylaxis tuberculosis vaccine
therapeutic tuberculosis vaccine
title Novel prophylactic and therapeutic multi-epitope vaccine based on Ag85A, Ag85B, ESAT-6, and CFP-10 of Mycobacterium tuberculosis using an immunoinformatics approach
title_full Novel prophylactic and therapeutic multi-epitope vaccine based on Ag85A, Ag85B, ESAT-6, and CFP-10 of Mycobacterium tuberculosis using an immunoinformatics approach
title_fullStr Novel prophylactic and therapeutic multi-epitope vaccine based on Ag85A, Ag85B, ESAT-6, and CFP-10 of Mycobacterium tuberculosis using an immunoinformatics approach
title_full_unstemmed Novel prophylactic and therapeutic multi-epitope vaccine based on Ag85A, Ag85B, ESAT-6, and CFP-10 of Mycobacterium tuberculosis using an immunoinformatics approach
title_short Novel prophylactic and therapeutic multi-epitope vaccine based on Ag85A, Ag85B, ESAT-6, and CFP-10 of Mycobacterium tuberculosis using an immunoinformatics approach
title_sort novel prophylactic and therapeutic multi epitope vaccine based on ag85a ag85b esat 6 and cfp 10 of mycobacterium tuberculosis using an immunoinformatics approach
topic multi-epitope vaccine
prophylaxis tuberculosis vaccine
therapeutic tuberculosis vaccine
url http://ophrp.org/upload/pdf/j-phrp-2024-0026.pdf
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