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An Epitope Platform for Safe and Effective HTLV-1-Immunization: Potential Applications for mRNA and Peptide-Based Vaccines
Authors:Guglielmo Lucchese  Hamid Reza Jahantigh  Leonarda De Benedictis  Piero Lovreglio  Angela Stufano
Affiliation:1.Department of Neurology, Medical University of Greifswald, 17475 Greifswald, Germany;2.Interdisciplinary Department of Medicine-Section of Occupational Medicine, University of Bari, 70124 Bari, Italy; (H.R.J.); (L.D.B.); (P.L.); (A.S.);3.Animal Health and Zoonosis Doctoral Program, Department of Veterinary Medicine, University of Bari, 70010 Bari, Italy
Abstract:Human T-cell lymphotropic virus type 1 (HTLV-1) infection affects millions of individuals worldwide and can lead to severe leukemia, myelopathy/tropical spastic paraparesis, and numerous other disorders. Pursuing a safe and effective immunotherapeutic approach, we compared the viral polyprotein and the human proteome with a sliding window approach in order to identify oligopeptide sequences unique to the virus. The immunological relevance of the viral unique oligopeptides was assessed by searching them in the immune epitope database (IEDB). We found that HTLV-1 has 15 peptide stretches each consisting of uniquely viral non-human pentapeptides which are ideal candidate for a safe and effective anti-HTLV-1 vaccine. Indeed, experimentally validated HTLV-1 epitopes, as retrieved from the IEDB, contain peptide sequences also present in a vast number of human proteins, thus potentially instituting the basis for cross-reactions. We found a potential for cross-reactivity between the virus and the human proteome and described an epitope platform to be used in order to avoid it, thus obtaining effective, specific, and safe immunization. Potential advantages for mRNA and peptide-based vaccine formulations are discussed.
Keywords:HTLV-1   vaccine   peptide   adjuvant   similarity   autoimmunity
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