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

Résumé fourni par la source

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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