In-silico development of a novel TLR2-mediating multi-epitope vaccine against Mycobacterium tuberculosis

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), still remains one of the leading causes of mortality worldwide. The elusive nature of this pathogen and its ability to develop drug resistance makes it a serious threat to global health. BCG, the only preventive vaccine for TB, has a limited efficacy and provides partial protection against the disease. A new effective recombinant vaccine capable of producing a stronger and more comprehensive immune response is required to address this global threat. In the present study, we adopted an in-silico approach to develop a multi-epitope vaccine by screening 198 "regulatory proteins" of Mtb H37Rv strain. Epitopes generated from these proteins were screened on the basis of antigenicity, cytokine profile, allergenicity, toxicity, conservancy and population coverage. Selected epitopes were docked with predominant MHC alleles that were used to develop a vaccine construct using suitable linkers and adjuvant. The construct was subjected to homology modelling, tertiary structure validation and refinement and was eventually docked with Toll-like receptor 2 receptor. Molecular dynamic simulation studies revealed stable interactions between the vaccine construct and TLR-2 receptor. The construct also displayed a high probability to elicit a protective immune response involving both humoral and cell-mediated components. In conclusion, the findings suggest that the constructed vaccine has the potential to induce a robust immune response against Mtb. However, further in-vitro and in-vivo studies are required to assess the safety, efficacy, and long-term protective effects of the vaccine construct.

The online version contains supplementary material available at 10.1007/s40203-025-00322-8.