In silico design of a promiscuous chimeric multi-epitope vaccine against Mycobacterium tuberculosis

Abstract

Tuberculosis (TB) is a global health threat, killing approximately 1.5 million people each year. The eradication of <i>Mycobacterium tuberculosis</i>, the main causative agent of TB, is increasingly challenging due to the emergence of extensive drug-resistant strains. Vaccination is considered an effective way to protect the host from pathogens, but the only clinically approved TB vaccine, Bacillus Calmette-Guérin (BCG), has limited protection in adults. Multi-epitope vaccines have been found to enhance immunity to diseases by selectively combining epitopes from several candidate proteins. This study aimed to design a multi-epitope vaccine against TB using an immuno-informatics approach. Through functional enrichment, we identified eight proteins secreted by <i>M. tuberculosis</i> that are either required for pathogenesis, secreted into extracellular space, or both. We then analyzed the epitopes of these proteins and selected 16 helper T lymphocyte epitopes with interferon-γ inducing activity, 15 cytotoxic T lymphocyte epitopes, and 10 linear B-cell epitopes, and conjugated them with adjuvant and Pan HLA DR-binding epitope (PADRE) using appropriate linkers. Moreover, we predicted the tertiary structure of this vaccine, its potential interaction with Toll-Like Receptor-4 (TLR4), and the immune response it might elicit. The results showed that this vaccine had a strong affinity for TLR4, which could significantly stimulate CD4⁺ and CD8⁺ cells to secrete immune factors and B lymphocytes to secrete immunoglobulins, so as to obtain good humoral and cellular immunity. Overall, this multi-epitope protein was predicted to be stable, safe, highly antigenic, and highly immunogenic, which has the potential to serve as a global vaccine against TB.