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The emergence of drug resistance has increased treatment difficulty, leaving the Bacillus Calmette-Gu\u00e9rin (BCG) vaccine as the only licensed preventative immunization available. This study focused on identifying the epitopes of <jats:italic>PknD<\/jats:italic> (<jats:italic>Rv0931c<\/jats:italic>) and <jats:italic>Rv0986<\/jats:italic> from <jats:italic>Mycobacterium tuberculosis<\/jats:italic>(<jats:italic>Mtb<\/jats:italic>) strain H37Rv using an in silico method. The goal was to develop a therapeutic mRNA vaccine for preventing CNS TB. The vaccine was designed to be non-allergenic, non-toxic, and highly antigenic. Codon optimization was performed to ensure effective translation in the human host. Additionally, the secondary and tertiary structures of the vaccine were predicted, and molecular docking with TLR-4 was carried out. A molecular dynamics simulation confirmed the stability of the complex. The results indicate that the vaccine structure shows effectiveness. Overall, the constructed vaccine exhibits ideal physicochemical properties, immune response, and stability, laying a theoretical foundation for future laboratory experiments.<\/jats:p>","DOI":"10.1371\/journal.pone.0307877","type":"journal-article","created":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T17:38:33Z","timestamp":1725644313000},"page":"e0307877","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":16,"title":["Development of innovative multi-epitope mRNA vaccine against central nervous system tuberculosis using in silico 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