title: Phase I clinical study of a peptide vaccination for hepatitis C virus-infected patients with different human leukocyte antigen-class I-A alleles.
abstract: Hepatitis C virus (HCV) infection has a high risk of liver cirrhosis and hepatocellular carcinoma at later stages. We recently identified a peptide derived from the HCV core protein capable of inducing both cellular and humoral responses to nearly all HCV-positive patients in Japan with different human leukocyte antigen (HLA)-class I-A alleles. To assess the safety and immune responses to this novel peptide, we conducted a phase I dose-escalation study of the vaccination for 26 HCV-positive patients who were either non-responders to the interferon-based therapy (n = 23) or refused it (n = 3). The regimen was well tolerated, with no severe vaccine-related toxicity. Twenty-five and 22 patients completed the first and second cycle vaccination (6 and 12 vaccine injections), respectively. After a series of six vaccine injections, peptide-specific CTL activity was augmented in peripheral blood mononuclear cells from 15 of 25 patient samples, with an expected optimal dose of 1 mg peptide. After 12 vaccine injections, peptide-specific IgG production was augmented in plasma from the majority of patients (15 of 22 patients) tested, but not in a dose-dependent fashion. There were two HCV RNA responders with >1 log declines. Among patients whose pre-vaccination levels of alanine aminotransferase and alpha feto-protein exceeded the normal ranges, a <30% decrease was found in 7 of 24 and three of six patients, respectively. Because of its tolerability and higher rate of immune boosting, this protocol is recommended for a phase II study to investigate its clinical efficacy.
authors: Department of Immunology and Immunotherapy, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors: Shigeru
authors: S
authors: Yutani
authors: Nobukazu
authors: N
authors: Komatsu
authors: Shigeki
authors: S
authors: Shichijo
authors: Kazumi
authors: K
authors: Yoshida
authors: Hiroko
authors: H
authors: Takedatsu
authors: Minoru
authors: M
authors: Itou
authors: Ryoko
authors: R
authors: Kuromatu
authors: Tatsuya
authors: T
authors: Ide
authors: Masatoshi
authors: M
authors: Tanaka
authors: Michio
authors: M
authors: Sata
authors: Akira
authors: A
authors: Yamada
authors: Kyogo
authors: K
authors: Itoh
mesh_terms: D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000517:prevention & control* / Q000821:virology; D005260:Female; D015234:HLA-A Antigens / Q000235:genetics*; D018936:Hepatitis C Antigens / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000150:complications / Q000235:genetics / Q000628:therapy*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008103:Liver Cirrhosis / Q000517:prevention & control / Q000821:virology; D008113:Liver Neoplasms / Q000517:prevention & control* / Q000821:virology; D008297:Male; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D022223:Vaccines, Subunit / Q000276:immunology / Q000627:therapeutic use; D014758:Viral Core Proteins / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D015234:HLA-A Antigens; D018936:Hepatitis C Antigens; D007074:Immunoglobulin G; D022223:Vaccines, Subunit; D014758:Viral Core Proteins