Designing a Novel Multi-Epitope Vaccine against HTLV-1 Related Adult T-Cell Leukemia/Lymphoma: An In Silico Approach

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Author(s): Elnaz Farahi, Mohammad Javad Mokhtari, Younes Ghasemi, Navid Nezafat*

Journal Name: Current Proteomics

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Background: Cancer is a genetic disorder, in which several factors like oncoviruses are involved. Among viruses, Human T-lymphotropic virus 1 (HTLV-1) is a human oncovirus that long-term infection leads to Adult T-cell leukemia/lymphoma (ATLL). The lack of vaccine against HTLV-1 and limited efficacy of available treatments for ATLL due to the weakness of immune system, led us to develop novel therapeutic\prophylactic epitope vaccine, which are able to potentiate immune system against HTLV-1.

Methods: In this research, the amino acid sequences of TAX, HBZ, gp62 and NY-ESO-1 were retrieved from the UniProt database. Afterwards, the bioinformatics analyses were performed to select the cytotoxic T lymphocytes (CTL) and helper T lymphocyte (HTL) epitopes using IEDB, RANKPEP, CTLpred and PA Complex servers. The selected epitopes along with RS09 protein adjuvant were connected to each other via proper amino acid linkers. RS09 adjuvant was used as a TLR4 agonist to assure the induction of immune response. Then, the three-dimensional model of protein vaccine was generated via Phyer2 software. In the next step, the optimization of final structure of protein vaccine was performed using GalaxyRefine, Galaxyloop and KOBAMIN servers.

Results: Evaluation of 3D protein vaccine with ERRAT, PROSA-web and Ramachandran plots, servers showed that the vaccine possesses the high-quality structure; moreover, the vaccine was antigen and non-allergen.

Conclusion: We believe that the designed vaccine candidate can stimulate cellular and humoral immunity effectively; however, the potency of vaccine should confirm via in vitro and in vivo immunological assays.

Keywords: ATLL, cancer; epitope, HTLV-1, RS09, vaccine

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(E-pub Ahead of Print)
DOI: 10.2174/1570164617999200717232832
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