In-silico identification of B-cell epitopes and immunological characterization of the vaccine chimera derived from MTB32A, Ag85B and ESAT-6 for control of Mycobacterium tuberculosis

Abstract

Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), poses a persistent global health challenge, with a staggering 10 million new cases and an estimated 1.6 million deaths reported in 2021 alone. The latent life cycle of TB, coupled with its propensity for multidrug resistance, underscores the gravity of this life-threatening disease. Till date, the Bacille Calmette-Guérin (BCG) vaccine remains the only anti-TB vaccine that is available and licensed for use but displays limited global efficacy as it primarily offers protection to infants and children hence not suitable for all age groups. In response to this critical gap, this study employed advanced in-silico techniques to design and characterize a vaccine chimera that can be further developed for control of tuberculosis in all populations. The study involved the identification of immunodominant linear B cell epitopes from MTB32A, Ag85B, and ESAT-6 proteins through advanced in-silico procedures. Subsequently, the vaccine chimera was designed by mapping five shortlisted epitopes from these proteins and incorporating a suitable adjuvant and linkers. The Beta defensin adjuvant was used in the construction. The resultant vaccine chimera comprised 258 amino acid residues, with a molecular weight of 26985.07 Da and a protrusion index (PI) of 6.47. Additional GRAVY analyses indicated the vaccine chimera to be hydrophilic. Overall, the vaccine chimera was predicted to be antigenic, highly immunogenic, non-allergenic and non-toxic hence ascertaining its safety for use. However, the chimera was found to be unstable, this can be explained by the fact that the construction was a synthetic one that does not exist in nature. Nevertheless, other findings obtained herein reaffirmed the potential of its applicability in vaccine construction. Moreover, the secondary and tertiary structure of this vaccine chimera were also predicted. Therefore, if subsequent experimental validations prove successful, the suggested vaccine chimera in this study could emerge as an effective therapeutic intervention against tuberculosis.