Designing a Novel Multi-Epitope Vaccine Against Htlv-1 Related Adult T-cell Leukemia/Lymphoma: An In Silico Approach

Abstract

\n\nCancer is a genetic disorder in which several factors like oncoviruses are\ninvolved. Among viruses, Human T-lymphotropic virus 1 (HTLV-1) is a human oncovirus whose\nlong-term infection leads to Adult T-Cell Leukemia/Lymphoma (ATLL).\n\n\n\nThe lack of a vaccine against HTLV-1 and limited efficacy of available treatments for ATLL due\nto the weakness of the immune system led us to develop novel therapeutic\\prophylactic epitope\nvaccine, which is able to potentiate the immune system against HTLV-1.\n\n\n\nIn this research, the amino acid sequences of TAX, HBZ, gp62 and NY-ESO-1 were retrieved\nfrom the UniProt database. Afterwards, the bioinformatics analyses were performed to select\nthe Cytotoxic T Lymphocytes (CTL) and Helper T Lymphocyte (HTL) epitopes using IEDB,\nRANKPEP, CTLpred and PA Complex servers. The selected epitopes, along with RS09 protein adjuvant,\nwere connected to each other via proper amino acid linkers.\n\n\n\nRS09 adjuvant was used as a TLR4 agonist to assure the induction of immune response. Then, the\nthree-dimensional model of the protein vaccine was generated via Phyer2 software. In the next\nstep, the optimization of the final structure of the protein vaccine was performed using\nGalaxyRefine, Galaxyloop and KOBAMIN servers.\n\n\n\nEvaluation of 3D protein vaccine with ERRAT, PROSA-web and Ramachandran plots\nservers showed that the vaccine possesses a high-quality structure; moreover, the vaccine was antigen\nand non-allergen.\n\n\n\nWe believe that the designed vaccine candidate can stimulate cellular and humoral immunity\neffectively; however, the potency of the vaccine should confirm via in vitro and in vivo immunological\nassays.\n