Analysis of Putative Epitope Candidates of Mycobacterium tuberculosis Against Pakistani Human Leukocyte Antigen Background: An Immunoinformatic Study for the Development of Future Vaccine

Abstract

Tuberculosis (TB), a chronic disease caused by Mycobacterium tuberculosis (Mtb), is a global health issue across the world. Pakistan ranks fifth among the countries, which are facing, a significantly great number of mortalities and morbidities due to TB. Unfortunately, all previously reported treatments are not successful for the eradication of TB. Here in this study, we report an emerging treatment option for this disease. We have applied immunoinformatics to predict highly conserved B and T-cell epitopes from Mtb, showing significant binding affinities to the frequent HLA alleles in the Pakistani population. A total of ten highly referenced and experimentally validated epitopes were selected from the Immune Epitope Database (IEDB), followed by their conservancy analysis using weblogos. The consensus sequences and variants derived from these sequences were examined, for their binding affinities, with prevalent HLA alleles of Pakistan. Moreover, the antigenic and allergenic natures of these peptides were also evaluated via Vaxijen and AllerTOP, respectively. Consequently, all potentially allergenic and non-antigenic, peptide fragments, were excluded from the analysis. Among all putative epitopes, three CD8 + T-cell epitopes were selected, as ideal vaccine candidates and, population coverage analysis revealed that the combination of these three peptides was covering, 67.28% Pakistani Asian and 57.15% mixed Pakistani populations. Likewise, eleven linear and six conformational or discontinuous B-cell epitopes were also marked as potential vaccine candidates based on their prediction score, non-allergenic nature, and antigenic properties. These epitopes, however, need the final validation via wet-lab studies. After their approval, these epitopes would be effective candidates for the future designing of epitope-based vaccines against Mtb infections in Pakistan.

An Immunoinformatic Strategy to Develop New Mycobacterium tuberculosis Multi-epitope Vaccine

“…Since the only approved TB vaccine, BCG, have demonstrated variable efficacy especially in adults and as live attenuated vaccine has low safety profile, lots of investigations have been focused on the development of anti-TB vaccines. There are also some investigations using immunoinformatic approach to design multi-epitope vaccines against TB (Bibi et al 2021 ; Mahmood et al 2021 ; Sharma et al 2021 ). In these studies, mostly known antigenic proteins or proteins in the exosome vesicles have been employed to find antigenic epitopes while in the present study a few new proteins with antigenic properties have been selected to find epitopes and to design the vaccine.…”