Design of a multi-epitope vaccine against drug-resistant mycobacterium tuberculosis and mycobacterium bovis using reverse vaccinology.

Akurut, E; Gavamukulya, Y; Mulindwa, J; Isiagi, M; Galiwango, R; Bbuye, M; Lujumba, I; Kiberu, D; Nabisubi, P; Kebirungi, G; +7 more...Kambugu, A; Castelnuovo, B; Nkurunungi, GORCID logo; Jjingo, D; Oketch, B; Kateete, DP; Mboowa, G and (2025) Design of a multi-epitope vaccine against drug-resistant mycobacterium tuberculosis and mycobacterium bovis using reverse vaccinology. Scientific reports, 15 (1). 27298-. ISSN 2045-2322 DOI: 10.1038/s41598-025-11768-3
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The global burden of Mycobacterium tuberculosis (M. tuberculosis) and Mycobacterium bovis (M. bovis), the rise of drug-resistant strains, necessitates an urgent need for developing more effective vaccines. This study employed an in-silico approach to design a multi-epitope vaccine targeting the PE_PGRS16 protein, a conserved virulence factor found across both species, including drug-resistant strains. PE_PGRS16 was chosen due to its extracellular localization, adhesion properties, and virulence characteristics, making it a promising vaccine target. Epitopes for B-cells, Cytotoxic T Lymphocytes, and Helper T Lymphocytes were selected based on antigenicity, non-toxicity, and immune response potential. The vaccine construct demonstrated favorable properties, including high antigenicity, solubility, and stability, with a low instability index (-31.31) and binding energy (-44.566) when docked to TLR4, suggesting its potential for immune activation. Griselimycin was incorporated as an adjuvant to enhance immunogenicity, as predicted by C-ImmSim simulations. Population coverage analysis for East Africa revealed high applicability, with 98.35% coverage for Class I epitopes, 100% coverage for Class II epitopes, and 100% combined coverage, with average hit values of 8.4, 12.26, and 20.66, respectively. These results suggest broad potential for global vaccine deployment. This study presents a novel multi-epitope vaccine targeting PE_PGRS16, with the potential to combat Mycobacterium tuberculosis and Mycobacterium bovis infections, including drug-resistant forms. Further experimental validation is necessary to confirm its efficacy and safety.


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