Abstract
Human T-cell lymphotropic virus type 1 (HTLV-1) is an infectious virus that has been linked to adult T cell leukemia /lymphoma, aggressive CD4-T cell malignancy and many other immune-related medical illnesses. So far, no effective vaccine is known to combat HTLV-1, hence, the current research work was performed to design a potential multi-epitope-based subunit vaccine (MEBV) by adopting the latest methodology of reverse vaccinology. Briefly, three highly antigenic proteins (Glycoprotein, Accessory protein, and Tax protein) with no or minimal (<37%) similarity with human proteome were sorted out and potential B- and T-cell epitopes were forecasted from them. Highly antigenic, immunogenic, non-toxic, non-allergenic and overlapping epitopes were short-listed for vaccine development. The chosen T-cell epitopes displayed a strong binding affinity with their corresponding Human Leukocyte Antigen alleles and demonstrated 95.8% coverage of the world’s population. Finally, nine Cytotoxic T Lymphocytes, six Helper T Lymphocytes and five Linear B Lymphocytes epitopes, joint through linkers and adjuvant, were exploited to design the final MEBV construct, comprising of 382 amino acids. The developed MEBV structure showed highly antigenic properties while being non-toxic, soluble, non-allergenic, and stable in nature. Moreover, disulphide engineering further enhanced the stability of the final vaccine protein. Additionally, Molecular docking analysis and Molecular Dynamics (MD) simulations confirmed the strong association between MEBV construct and human pathogenic immune receptor TLR-3. Repeated-exposure simulations and Immune simulations ensured the rapid antigen clearance and higher levels of cell-mediated immunity, respectively. Furthermore, MEBV codon optimization and in-silico cloning was carried out to confirm its augmented expression. Results of our experiments suggested that the proposed MEBV could be a potential immunogenic against HTLV-1; nevertheless, additional wet lab experiments are needed to elucidate our conclusion.
Highlights
The Human T-cell lymphotropic virus 1 (HTLV-1) is a part of family “Retroviridae”, subfamily “Orthoretrovirinae” and genus “Deltaretrovirus” [1]
Full proteome of HTLV-1 was downloaded from Uniprot (Proteome ID: UP000007683) HTLV-1 proteome consisted of nine different proteins
Antigenicity of all of these proteins was evaluated by VaxiJen v.2.0, results of which represented that only six proteins had vaxijan score >0.45 the sequence of only these proteins was submitted to Blastp for identifying their similarity with human proteins
Summary
The Human T-cell lymphotropic virus 1 (HTLV-1) is a part of family “Retroviridae”, subfamily “Orthoretrovirinae” and genus “Deltaretrovirus” [1]. It is the first human retrovirus to be ever reported, having been identified independently in the United States [2] and Japan [3] in 1980 and 1982 respectively. HTLV-1 is widespread in the United States, South America, Africa, Oceania, Caribbean and Japan [2, 6,7,8]. Polygamy and insecure sex are the potential risk factors of HTLV-1 infection, whereas, transmission within humans occur due to injecting drugs via parenteral routes, blood transfusion and breastfeeding [9,10,11]
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