Mycobacterium tuberculosis resides in alveolar macrophages as a non-dividing and dormant state causing latent tuberculosis. Currently, no vaccine available against the latent tuberculosis. Latent Mtb expresses ~48 genes under the control of DosR regulon. Among these, putative nitroreductases have significantly high expression levels, help Mtb to cope up with nitrogen stresses, and possess antigenic properties. In the current study, immunoinformatics methodologies are applied to predict the promiscuous antigenic T-cell epitopes from putative nitro-reductases, Rv2032, Rv3127, Rv3129, and Rv3131 of the DosR regulon. The promiscuous antigenic T-cell epitopes prediction was performed on the basis of their potential to induce an immune response and forming a stable interaction with the HLA alleles. IFN-γ and IL-4 inducing abilities were also predicted for the MHC-II class. The highest antigenic promiscuous epitopes were assembled for designing an in-silico vaccine construct. A TLR-2 agonist Phenol-soluble modulin alpha 4 (PsmA4) was exploited as an adjuvant. Molecular docking and Molecular Dynamics Simulations were used to predict the stability of vaccine construct with TLR-2 immune receptor. The predicted promiscuous epitopes may be helpful in the construction of a subunit vaccine against LTBI, which can also be administered along with BCG to increase the efficacy of BCG. Experimental validation is a prerequisite of in-silico designed vaccine construct for protection against TB infection.
Copyright © 2018. Published by Elsevier B.V.