A PEPTIDE-BASED HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I VACCINE CONTAINING T-CELL AND B-CELL EPITOPES THAT INDUCES HIGH TITERS OF NEUTRALIZING ANTIBODIES

We have recently identified the principal linear neutralizing B cell epitopes of human T cell leukemia virus type (HTLV-I) on the envelope protein gp46, amino acids (aa) 187-199, by using a number of human mAbs. We therefore propose that this region would be a good candidate for a peptide-based HTLV-I vaccine. To develop a peptide-based vaccine that can induce a high titer of neutralizing Abs against HTLV-I, we first synthesized peptides of various lengths containing aa187-199. Because the addition of gp46 aa181-186 or aa200-210 to either the N-terminus or C-terminus of SP187-199 did not alter the antigenicity of the principal neutralizing determinant, we prepared two peptide-based vaccines, MAP181-203 and MAP181-210, by conjugating SP181-203 and SP181-210 with a branched polylysine oligomer. In rabbits, x4 to x8 and x8 to x64 titers of the neutralizing Abs were induced by immunization with MAP181-203 and MAP181-210, respectively. Furthermore, high titers of neutralizing Abs (x40 to x320) were elicited in five different strains of rats by immunization with MAP181-210. We also identified the major T cell epitope on gp46 aa194-210 in various Strains of rats immunized with MAP181-210. Furthermore, the peripheral T lymphocytes obtained from the majority of HTLV-I-infected patients including HTLV-1-associated myelopathy/tropical spastic paraparesis, adult T cell leukemia/lymphoma, and healthy carriers, proliferated in response to the peptides containing aa194-210. These results indicated that MAP181-210 contains a T cell helper epitope on aa194-210 not only in rats and rabbits, but also in humans with various HLA haplotypes. It is therefore possible that MAP181-210 could become one of the candidates for a peptide-based HTLV-I vaccine for human use.