Design of multi-epitope based vaccine against Mycobacterium tuberculosis: a subtractive proteomics and reverse vaccinology based immunoinformatics approach

Tuberculosis is an airborne transmissible disease caused by Mycobacterium tuberculosis that infects millions of lives worldwide. There is still no single comprehensive therapy or preventative available for the lethal illness. Currently, the available vaccine, BCG is ineffectual in preventing the prophylactic adult pulmonary TB and reactivation of latent tuberculosis. Therefore, this investigation was intended to design a new multi-epitope vaccine that can address the existing problems. The subtractive proteomics approach was implemented to prioritize essential, virulence, druggable, and antigenic proteins as suitable vaccine candidates. Furthermore, a reverse vaccinology-based immunoinformatics technique was employed to identify potential B-cell, helper T lymphocytes (HTL), and cytotoxic T lymphocytes (CTL) epitopes from the target proteins. Immune-stimulating adjuvant, linkers, and PADRE (Pan HLA-DR epitopes) amino acid sequences along with the selected epitopes were used to construct a chimeric multi-epitope vaccine. The molecular docking and normal mode analysis (NMA) were carried out to evaluate the binding mode of the designed vaccine with different immunogenic receptors (MHC-I, MHC-II, and Tlr4). In addition, the MD simulation, followed by essential dynamics study and MMPBSA analysis, was carried out to understand the dynamics and stability of the complexes. In-silico cloning was accomplished using E.coli as an expression system to express the designed vaccine successfully. Finally, the immune simulation study has foreseen that our designed vaccine could induce a significant immune response by elevation of different immunoglobulins in the host. However, there is an imperative need for the experimental validation of the designed vaccine in animal models to confer effectiveness and safety.

Automated summary

Tuberculosis is a global airborne transmissible disease caused by Mycobacterium tuberculosis. The current vaccine, BCG, is ineffective in preventing adult pulmonary TB and latent tuberculosis. In this study, a new multi-epitope vaccine was designed using subtractive proteomics and immunoinformatics techniques. The designed vaccine showed promising binding modes with immunogenic receptors and demonstrated stability in molecular dynamics simulations. In silico cloning successfully expressed the designed vaccine, and immune simulation predicted a significant immune response. However, experimental validation in animal models is needed for effectiveness and safety.