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Multi-epitope vaccine candidates based on mycobacterial membrane protein large (MmpL) proteins against Mycobacterium ulcerans.


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.

SUBMITTER: Ishwarlall TZ 

PROVIDER: S-EPMC10645115 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Multi-epitope vaccine candidates based on mycobacterial membrane protein large (MmpL) proteins against <i>Mycobacterium ulcerans</i>.

Ishwarlall Tamara Z TZ   Adeleke Victoria T VT   Maharaj Leah L   Okpeku Moses M   Adeniyi Adebayo A AA   Adeleke Matthew A MA  

Open biology 20231108 11


Buruli ulcer (BU) is a neglected tropical disease. It is caused by the bacterium <i>Mycobacterium ulcerans</i> and is characterized by skin lesions. Several studies were performed testing the Bacillus Calmette-Guérin (BCG) vaccine in human and animal models and <i>M. ulcerans-</i>specific vaccines in animal models. However, there are currently no clinically accepted vaccines to prevent <i>M. ulcerans</i> infection. The aim of this study was to identify T-cell and B-cell epitopes from the mycobac  ...[more]

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