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Multi-epitope vaccine candidates based on mycobacterial membrane protein large (MmpL) proteins against Mycobacterium ulcerans
- Source :
- Open Biology, Vol 13, Iss 11 (2023)
- Publication Year :
- 2023
- Publisher :
- The Royal Society, 2023.
-
Abstract
- Buruli ulcer (BU) is a neglected tropical disease. It is caused by the bacterium Mycobacterium ulcerans and is characterized by skin lesions. Several studies were performed testing the Bacillus Calmette-Guérin (BCG) vaccine in human and animal models and M. ulcerans-specific vaccines in animal models. However, there are currently no clinically accepted vaccines to prevent M. ulcerans infection. The aim of this study was to identify T-cell and B-cell epitopes from the mycobacterial membrane protein large (MmpL) proteins of M. ulcerans. These epitopes were analysed for properties including antigenicity, immunogenicity, non-allergenicity, non-toxicity, population coverage and the potential to induce cytokines. The final 8 CD8+, 12 CD4+ T-cell and 5 B-cell epitopes were antigenic, non-allergenic and non-toxic. The estimated global population coverage of the CD8+ and CD4+ epitopes was 97.71%. These epitopes were used to construct five multi-epitope vaccine constructs with different adjuvants and linker combinations. The constructs underwent further structural analyses and refinement. The constructs were then docked with Toll-like receptors. Three of the successfully docked complexes were structurally analysed. Two of the docked complexes successfully underwent molecular dynamics simulations (MDS) and post-MDS analysis. The complexes generated were found to be stable. However, experimental validation of the complexes is required.
Details
- Language :
- English
- ISSN :
- 20462441
- Volume :
- 13
- Issue :
- 11
- Database :
- Directory of Open Access Journals
- Journal :
- Open Biology
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.b8226adaddc546a0a70d915791c434f5
- Document Type :
- article
- Full Text :
- https://doi.org/10.1098/rsob.230330