DOI: 10.4103/bbrj.bbrj_22_26 ISSN: 2588-9834

In silico Design of a Novel Multi-epitope Chimeric Vaccine Targeting Mycobacterium tuberculosis Specific Antigens

R. Princess, A. Annie Aglin, Arul Jayanthi Antonisamy
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Background:

While the Bacillus Calmette–Guérin vaccine provides early-life protection, its waning efficacy in adults remains a critical barrier to global tuberculosis (TB) control. Despite several candidates targeting region of difference (RD) loci proteins entering clinical trials, a successful replacement has yet to emerge. Consequently, the design of multi-valent, multi-epitope peptide vaccine can elicit the robust humoral and cell-mediated immune responses required for sustained, long-term protection against Mycobacterium tuberculosis .

Methods:

To develop the vaccine, 38 RD-loci proteins from the H37Rv strain were screened for CD4 + and CD8 + epitopes based on their binding affinity to common Human Leukocyte Antigen (HLA) allele. The construct was validated in silico for stability, safety, and nonallergenicity. The vaccine’s efficacy was further evaluated through molecular docking followed by molecular dynamics (MD) simulations to confirm robust binding affinity and stability with the toll-like receptor (TLR) 2 and TLR4 receptor.

Results:

A total of 7 B-cell, 9 cytotoxic T-lymphocyte (CTL), and 11 helper T lymphocyte epitopes were predicted and strategically integrated with the adjuvant human beta defensin-3 and neutrophil peptide-1 at N-and C-termini using flexible linkers to enhance immunogenicity. Comprehensive in silico profiling validated the chimeric construct as nontoxic, nonallergenic, and highly antigenic. Furthermore, molecular docking analysis demonstrated a robust interaction with the TLR2 receptor, characterized by a significant binding affinity, suggesting high potential for initiating a potent immune response.

Conclusion:

Collectively, these in silico findings demonstrate that the designed multi-epitope vaccine possesses the necessary structural and immunogenic properties to elicit robust humoral and cellular immune responses. The construct’s high antigenicity, combined with its stable interaction with key immune receptors, positions it as a highly promising candidate for TB prevention.

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