International journal of mycobacteriology · 2026
In silico Designing of a Multiepitope Vaccine using the Hallmark Proteins of Mycobacterium tuberculosis Involved in Different Aspects of Virulence.
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Fayaz Haleema, Ali Waseem, Shrivastava Gauri, Prandiyal Shivangi, Ehtesham Nasreen Z, Hasnain Seyed E, Alam Anwar
Аннотация
BACKGROUND: Mycobacterium tuberculosis ( M.tb ) remains a leading global cause of mortality. The current Bacillus Calmette-Guérin vaccine lacks efficacy in adults and fails to generate a long-term memory response. With the rise of multidrug-resistant strains, there is an urgent need for novel vaccines that can provide broader protection. This study aimed to design a multiepitope vaccine (MEV) targeting hallmark proteins involved in different aspects of M.tb virulence.
METHODS: Four unique M.tb proteins, Rv1507A (role in memory response), Rv1509 (role in phagolysosomal escape), Rv1954A (role in macrophage activation/antigen presentation), and Rv2231A (role in persistence) were selected. In silico analyses were performed to identify epitopes with high-binding affinity for Toll-like receptors (TLRs). Two MEVs were optimized for codon and were linked with adjuvants that could bind with TLR4 or TLR2 (TLR4-laterosporulin and TLR2-PorB). Physicochemical properties, allergenicity, toxicity, and structural stability were evaluated, followed by molecular docking with TLR receptors, molecular dynamic (MD) simulation, in silico cloning, and immune simulations.
RESULTS: Both MEVs exhibited favorable biophysical properties and high structural stability. Molecular docking confirmed strong binding affinities with TLR2 and TLR4 receptors, suggesting a robust activation of innate and adaptive immunity. Immunological simulations predicted a potent immune response characterized by high cytokine production and memory cell differentiation. The designed MEV demonstrated approximately 90% global population coverage.
CONCLUSIONS: The designed MEVs effectively bridge gaps in existing TB immunization by targeting multiple aspects of M.tb pathogenesis. These in silico leads provide a promising framework for preclinical studies, potentially moving toward a more effective clinical solution against TB.
METHODS: Four unique M.tb proteins, Rv1507A (role in memory response), Rv1509 (role in phagolysosomal escape), Rv1954A (role in macrophage activation/antigen presentation), and Rv2231A (role in persistence) were selected. In silico analyses were performed to identify epitopes with high-binding affinity for Toll-like receptors (TLRs). Two MEVs were optimized for codon and were linked with adjuvants that could bind with TLR4 or TLR2 (TLR4-laterosporulin and TLR2-PorB). Physicochemical properties, allergenicity, toxicity, and structural stability were evaluated, followed by molecular docking with TLR receptors, molecular dynamic (MD) simulation, in silico cloning, and immune simulations.
RESULTS: Both MEVs exhibited favorable biophysical properties and high structural stability. Molecular docking confirmed strong binding affinities with TLR2 and TLR4 receptors, suggesting a robust activation of innate and adaptive immunity. Immunological simulations predicted a potent immune response characterized by high cytokine production and memory cell differentiation. The designed MEV demonstrated approximately 90% global population coverage.
CONCLUSIONS: The designed MEVs effectively bridge gaps in existing TB immunization by targeting multiple aspects of M.tb pathogenesis. These in silico leads provide a promising framework for preclinical studies, potentially moving toward a more effective clinical solution against TB.