A new epitope peptide derived from hepatitis C virus 1b possessing the capacity to induce cytotoxic T-lymphocytes in HCV1b-infected patients with HLA-A11, -A31, and -A33.

Abstract

Hepatitis C virus (HCV) frequently causes chronic hepatitis, cirrhosis, and hepatocellular carcinoma after long-term persistent infection. Among various genotypes of HCV, HCV1b is resistant to standard interferon therapy, and thus the development of new treatment modality is needed. To provide a scientific basis for specific immunotherapy for HCV1b, we investigated HCV1b-derived epitope peptides recognized by human leukocyte antigen (HLA)-A11, -A31, or -A33-restricted cytotoxic T-lymphocytes (CTLs), and report here three novel vaccine candidate peptides selected by both antibody screening and CTL-inducing capacity from among 46 peptides of conserved regions of HCV1b sequences with binding motifs to HLA-A11, -A31, and -A33. Significant levels of IgG reactive to each of the three peptides were detected in the plasma of more than 50% of the HCV1b(+) patients. One peptide at positions 30-39 of the core protein induced peptide-specific CTLs from peripheral blood mononuclear cells (PBMCs) of HLA-A11(+), -A31(+), and -A33(+) patients. The other two peptides at positions 35-43 of the core protein and at positions 918-926 of the non-structural protein 2 also induced peptide-specific CTLs from the PBMCs of HLA-A11(+) and -A33(+) patients. Therefore, the peptide at positions 30-39 of the core protein could be an appropriate target molecule of specific immunotherapy for all HLA-A11(+), -A31(+), and -A33(+) patients with HCV1b-related diseases.