Design of a Multi-Epitope Vaccine against Tuberculosis from Mycobacterium tuberculosis PE_PGRS49 and PE_PGRS56 Proteins by Reverse Vaccinology

Abstract

Tuberculosis is a disease caused by Mycobacterium tuberculosis, representing the second leading cause of death by an infectious agent worldwide. The available vaccine against this disease has insufficient coverage and variable efficacy, accounting for a high number of cases worldwide. In fact, an estimated third of the world’s population has a latent infection. Therefore, developing new vaccines is crucial to preventing it. In this study, the highly antigenic PE_PGRS49 and PE_PGRS56 proteins were analyzed. These proteins were used for predicting T- and B-cell epitopes and for human leukocyte antigen (HLA) protein binding efficiency. Epitopes GGAGGNGSLSS, FAGAGGQGGLGG, GIGGGTQSATGLG (PE_PGRS49), and GTGWNGGKGDTG (PE_PGRS56) were selected based on their best physicochemical, antigenic, non-allergenic, and non-toxic properties and coupled to HLA I and HLA II structures for in silico assays. A construct with an adjuvant (RS09) plus each epitope joined by GPGPG linkers was designed, and the stability of the HLA-coupled construct was further evaluated by molecular dynamics simulations. Although experimental and in vivo studies are still necessary to ensure its protective effect against the disease, this study shows that the vaccine construct is dynamically stable and potentially effective against tuberculosis.

Discovering peptides and computational investigations of a multiepitope vaccine target Mycobacterium tuberculosis

“…In this study, we aim to design a MEV candidate against tuberculosis to contribute towards the End MTB Strategy. Several vaccines for MT have been developed to provide possible candidates for novel vaccine designs [ 15 , 18 , 19 , 59 ]. While a few new proteins with antigenic qualities were chosen for the current study to identify epitopes and develop the vaccine, most known antigenic proteins or proteins found in exosome vesicles were used in these previous studies to uncover antigenic epitopes.…”

“…Besides, the advantage of epitope vaccines over traditional subunit vaccines lies in the ability to combine immunodominant human HTL, CTL, and LBL epitopes from different antigens, thereby enhancing immunogenicity and reducing adverse effects. Currently, many MEVs based on epitope designs from multiple antigens against tuberculosis are being researched [ [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] ]. Among them, Jiang et al selected 17 latent tuberculosis infection and regions of difference (LTBI-RD) antigens (Rv1511, Rv1736c, Rv1737c, Rv1980c, Rv1981c, Rv2031c, Rv2626c, Rv2653c, Rv2656c, Rv2659c, Rv2660c, Rv3425, Rv3429, Rv3872, Rv3873, Rv3878, and Rv3879) to identify immunodominant epitopes [ 12 ].…”