Epitopes described in "Therapeutic vaccination of chronic hepatitis C nonresponder patients with the peptide vaccine IC41."

Article Authors:Christoph S Klade; Heiner Wedemeyer; Thomas Berg; Holger Hinrichsen; Grazyna Cholewinska; Stefan Zeuzem; Hubert Blum; Michael Buschle; Sandra Jelovcan; Vera Buerger; Erich Tauber; Juergen Frisch; Michael P Manns
Article Title:Therapeutic vaccination of chronic hepatitis C nonresponder patients with the peptide vaccine IC41.
Reference Detail
Reference ID:1012332
Abstract:BACKGROUND & AIMS: IC41 is a synthetic peptide vaccine containing 7 relevant hepatitis C virus (HCV) T-cell epitopes and the T helper cell (Th)1/Tc1 adjuvant poly-L-arginine. IC41 has been shown to be safe and to induce HCV-specific interferon (IFN)-gamma-secreting CD4+ and CD8+ T cells in healthy volunteers. We aimed to investigate whether IC41 is able to induce HCV-specific T-cell responses also in chronic hepatitis C patients. METHODS: Sixty HLA-A2-positive chronic HCV patients not responding to or relapsing from standard therapy were randomized in a double-blind phase II study into 5 groups to receive 6 vaccinations of IC41 (3 different dose groups), HCV peptides alone, or poly-L-arginine alone. RESULTS: IC41 was well tolerated, and no drug-related serious adverse events or induction of hepatitis were observed. T-cell proliferation was recorded in up to 67% of patients in the 3 IC41 vaccine groups but only in 17% of patients treated with peptides alone. IFN-gamma enzyme-linked immunospot assay responses were observed exclusively in the IC41 groups with response rates up to 42%. There were 3 RNA responders with transient >1-log declines of HCV serum RNA associated with the strongest IFN-gamma enzyme-linked immunospot assay values within all 60 patients. CONCLUSIONS: This study showed that the HCV peptide vaccine IC41 can induce HCV-specific Th1/Tc1 responses in a subset of difficult to treat HCV nonresponder patients despite persisting viremia. However, changes in HCV RNA occurred only in single patients. Because strongest T-cell responses were associated with HCV RNA decline, further studies with optimized vaccine regimens and combination therapies have been initiated.
Affiliations:Intercell AG, Vienna, Austria.
Reference Type:Literature
PubMed ID:18471515
Journal Volume:134
Article Pages:1385-95
Journal ISSN:1528-0012
Article Chemical List:RNA, Viral;Vaccines, Subunit;Viral Vaccines
Article MeSH List:Adult; Aged; CD4-CD8 Ratio; Cell Proliferation; Double-Blind Method; Female; Follow-Up Studies; Hepacivirus(genetics; immunology ); Hepatitis C, Chronic(immunology; therapy; virology ); Humans; Male; Middle Aged; RNA, Viral(genetics ); T-Lymphocytes(immunology; pathology ); Treatment Outcome; Vaccination(methods ); Vaccines, Subunit; Viral Vaccines(therapeutic use )
Curation Last Updated:2015-07-24 20:08:52