Basic research for the development of peptide vaccination against Hepatitis C virus infection

点击翻译按钮获取中文摘要

Identification of CTL-epitope peptides: We selected and synthesized 44 9-mer or 10-mer peptides that were theoretically bind to HLA-A24 molecule from HCV1 b-derived protein by in silico analysis. We further picked up 6 peptides by patients' IgG antibody screening from the 44 peptides and CTL-inducing activity of the 6 peptides were subsequently examined using HCV-infected patients' peripheral blood mononuclear cells. Finally, we identified 3 peptides that are able to induce CTL in HLA-A24 patients (Hepatology Research, 2007). We also identified HLA-A3 supertype-restricted CTL-epitope peptides using similar strategy. Namely, we selected 46 peptides that were theoretically bind to HLA-A3 supertype (HLA-A3, -All, -A31, -A33) molecule from HCV1 b proteins by in silico analysis and finally 3 peptides that are able to induce CTL in HLA-A3 supertype patients were identified (Cancer Immunology Immunotherapy, 2007). The HLA-A2, -A24, and -A3 supertype are found in 40%, 60%, and 44%, respectivel … More y, of Japanese. Therefore, the previously identified vaccine candidate peptides for HLA-A2, together with the newly identified peptides for HLA-A24 and-A3 supertype patients, are able to cover the majority of HCV1 b patients in Japan.Anti-HCV peptide antibody as bio-marker: Relationship between serum IgG antibodies reactive to the CTL-epitope peptides and clinical status of HCV1 b-infected patients was analyzed. The serum IgG levels reactive to Core 35-44 peptide were found to correlate, with disease progression, such as progression from chronic hepatitis to liver cirrhosis or hepatocellular carcinoma. In contrast, the serum IgG levels to NS5A 2132-2142 peptide expressed reverse correlation to the disease progression (Med. Microbiol. Immunol., 2007).Clinical trial of peptide vaccination: To assess the safety and immune responses to a peptide vaccination of HCV1 b-derived peptides, 12 HCV1 b-positive patients, who were unresponsive to interferon-based therapy, were enrolled in the trial and safety and immunological effects of the vaccination were confirmed (Vaccine, 2007). Less