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Novel prophylactic and therapeutic multi-epitope vaccine based on Ag85A, Ag85B, ESAT-6, and CFP-10 of Mycobacterium tuberculosis using an immunoinformatics approach.
Nugraha, Muhammad Fikri; Changestu, Daniel Alexander; Ramadhan, Rizky; Salsabila, Tasya; Nurizati, Arsila; Pratiwi, Sari Eka; Ysrafil, Ysrafil.
Affiliation
  • Nugraha MF; Medical Program, Faculty of Medicine, Universitas Tanjungpura, Pontianak, Indonesia.
  • Changestu DA; Medical Program, Faculty of Medicine, Universitas Tanjungpura, Pontianak, Indonesia.
  • Ramadhan R; Medical Program, Faculty of Medicine, Universitas Tanjungpura, Pontianak, Indonesia.
  • Salsabila T; Medical Program, Faculty of Medicine, Universitas Tanjungpura, Pontianak, Indonesia.
  • Nurizati A; Medical Program, Faculty of Medicine, Universitas Tanjungpura, Pontianak, Indonesia.
  • Pratiwi SE; Department of Biology and Pathobiology, Faculty of Medicine, Universitas Tanjungpura, Pontianak, Indonesia.
  • Ysrafil Y; Department of Pharmacotherapy, Faculty of Medicine, Universitas Palangka Raya, Palangka Raya, Indonesia.
Osong Public Health Res Perspect ; 15(4): 286-306, 2024 Aug.
Article in En | MEDLINE | ID: mdl-39091165
ABSTRACT

BACKGROUND:

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.
Key words

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Osong Public Health Res Perspect Year: 2024 Document type: Article Affiliation country: Indonesia Country of publication:

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Osong Public Health Res Perspect Year: 2024 Document type: Article Affiliation country: Indonesia Country of publication: