The aim of this study was to predict promiscuous vaccine candidates against Mycobacterium tuberculosis (MTb) using in silico reverse vaccinology. Antigenic peptides from selected MTb strain LJ319 (4,025 proteins) were analyzed by various immunoinformatics tools; from which 165 outer membrane proteins (OMPs) suitable for vaccine designing were predicted. Further antigenicity, allergenicity, transmembrane α-helices, and solubility filters refine this number to 16 OMPs common in other members of Tb complex. By further analysis, T-cell and B-cell epitopes were predicted and subjected to characterization studies. After characterization, 26 promiscuous Epitopic peptides (MHC I: 4, MHC II: 7, and B cell: 15) were screened and joined to form 3 possible vaccine constructs (VC1, VC2, and VC3). To enhance immunomodulating effect of these constructs adjuvants (Accession No. WP_003403353.1, WP_031737436.1, and WP_094028633.1), and PADRE sequence (AKVAAWTLKAAAC) were added. The physiochemical characterization and molecular docking studies of vaccine constructs with HLA genes revealed VC1 can be further studied to control host and Tb interactions as it had the highest binding score was also a safe and immunogenic construct. Further studies are needed to ensure the expression and translation efficiency of the potential vaccine construct.
Key words: Vaccine; Tuberculosis; Drug resistance; in silico; Epitope; IEDB
|
