Harnessing bioinformatics for the development of a promising multi-epitope vaccine against tuberculosis: The ZL9810L vaccine

Tuberculosis (TB) is a global infectious disease posing a serious threat to human health, caused by Mycobacterium tuberculosis (MTB) infection. Although vaccination is the most effective way to prevent and control TB, the existing Bacillus Calmette–Guérin (BCG) vaccine exhibits limited protective efficacy in adult pulmonary TB. Therefore, developing a novel TB vaccine is an urgent need. This study designed a novel multi-epitope vaccine (MEV) to combat MTB infection, utilizing bioinformatics and immunoinformatics approaches. Dominant epitopes of helper T lymphocytes (HTL), cytotoxic T lymphocytes (CTL), and B lymphocytes were selected from antigens of MTB to construct the MEV. To enhance the targeting and immunogenicity of the vaccine, toll like receptor (TLR) agonists and PADRE helper peptides were incorporated into the design. In addition, comprehensive predictions have been made on the physicochemical properties, three-dimensional structure, spatial conformation, and molecular interactions with TLRs of MEVs. These evaluations also extend to the exploration of their immunological characteristics. A novel MEV named ZL9810L was successfully constructed, based on 8 HTL epitopes, 9 CTL epitopes, 10 B lymphocyte epitopes, Toll-like receptor agonists, and auxiliary peptides. Bioinformatics analysis demonstrated that the ZL9810L vaccine has excellent immunogenicity and antigenicity, non-toxicity, and non-sensitization capability, capable of significantly inducing a strong immune response and solubility, with scores of 2.21451, 0.8913, and 0.455 respectively. Moreover, the global population coverage of HLA class I and II allele genes by the ZL9810L vaccine reached 72.89 % and 81.49 %, respectively. Molecular docking analysis indicated good binding capacities of the ZL9810L vaccine to TLR2 and TLR4 receptors, with binding energies of −1028.5 kcal/mol and −1018.8 kcal/mol respectively. Immune simulation predicted that the vaccine could effectively activate innate and adaptive immune cells, including NK cells, macrophages, B lymphocytes, and T lymphocytes. As a candidate for a novel TB vaccine, the ZL9810L vaccine exhibits significant immunogenicity and antigenicity, with no toxicity or allergenicity. The ZL9810L vaccine designed in this study provides a new vaccine candidate for TB control and prevention. [Display omitted] •Design of novel MEV ZL9810L against MTB using bioinformatics and immunoinformatics.•Immunodominant epitopes identified cover HLA class I/II in