A peptide-based human T cell leukemia virus type I vaccine containing T 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 I (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-I-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.
Baba
E
E
First Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Nakamura
M
M
Ohkuma
K
K
Kira
J
J
Tanaka
Y
Y
Nakano
S
S
Niho
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D015480:Deltaretrovirus Antibodies / Q000096:biosynthesis* / Q000276:immunology; D015485:Deltaretrovirus Antigens / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology*; D005260:Female; D015686:Gene Products, env / Q000276:immunology*; D015490:HTLV-I Infections / Q000097:blood / Q000276:immunology; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000276:immunology*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015682:Retroviridae Proteins, Oncogenic / Q000276:immunology*; D016415:Sequence Alignment; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology
D015480:Deltaretrovirus Antibodies; D015485:Deltaretrovirus Antigens; D000939:Epitopes; D015686:Gene Products, env; D010446:Peptide Fragments; D011947:Receptors, Antigen, B-Cell; D011948:Receptors, Antigen, T-Cell; D015682:Retroviridae Proteins, Oncogenic; D014765:Viral Vaccines; C055266:gp46 protein, Human T-cell leukemia virus type I