Evaluation of peptide based vaccines and inhibitors to prevent the onset of HTLV-I associated diseases

HTLV-1 is the etiologic agent of ATL, HAM/TSP, as well as other inflammatory disorders. In the absence of a prophylactic vaccine for HTLV-1 or effective treatment for HAM/TSP, three peptide based strategies were evaluated. Prophylactic vaccination was evaluated using two B-cell epitope immunogens derived from the envelope glycoprotein in squirrel monkeys. Protective efficacy of the peptides could not be adequately evaluated because all monkeys spontaneously resolved the challenge with EVO/1540 cells. The stronger the cytolytic response against HTLV-1, the less likely one is to develop HAM/TSP. To increase the cytolytic responses of HTLV-1 infected individuals, computer algorithms were used to identify HLA-A*0201 restricted peptides from Gag, Tax, and Pol proteins. Peptides with optimal anchor residues were synthesized as wild-type epitopes, but peptides with suboptimal anchor residues were synthesized along with epitope enhanced mutants that possessed optimal anchor residues. Enhanced mutants increased cytolytic responses against the wild-type epitope, but were unable to lyse an HLA-A*0201 positive, HTLV-1 infected cell line. These results suggest that the Tax 11-19 epitope may be the only relevant HLA-A*0201 restricted epitope for vaccination. HAM/TSP patients generally have an elevated provirus load, which may contribute to disease. To limit cell-to-cell transmission of virus, peptide fusion inhibitors were evaluated for their ability to inhibit HTLV-1-mediated syncytia. Strategies employed included the use of L-amino acid and retro-inverso peptides form the P400 and P197 regions of Env. This dissertation shows three different peptide based approaches that could be used to combat various aspects of HTLV-1 and associated diseases.