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

• Published in: Open biology Vol. 13; no. 11; p. 230330
• Main Authors: Ishwarlall, Tamara Z., Adeleke, Victoria T., Maharaj, Leah, Okpeku, Moses, Adeniyi, Adebayo A., Adeleke, Matthew A.
• Format: Journal Article
• Language: English
• Published: The Royal Society 08-11-2023
• Subjects: Buruli ulcer; immunoinformatics; Mycobacterium ulcerans; vaccine design
• ISSN: 2046-2441; 2046-2441
• DOI: 10.1098/rsob.230330

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.