title: Therapeutic vaccination of chronic hepatitis C nonresponder patients with the peptide vaccine IC41.
abstract: OBJECTIVE
  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.
authors.affiliation: Intercell AG, Vienna, Austria.
authors.forename: Christoph S
authors.initials: CS
authors.lastname: Klade
authors.forename: Heiner
authors.initials: H
authors.lastname: Wedemeyer
authors.forename: Thomas
authors.initials: T
authors.lastname: Berg
authors.forename: Holger
authors.initials: H
authors.lastname: Hinrichsen
authors.forename: Grazyna
authors.initials: G
authors.lastname: Cholewinska
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.forename: Hubert
authors.initials: H
authors.lastname: Blum
authors.forename: Michael
authors.initials: M
authors.lastname: Buschle
authors.forename: Sandra
authors.initials: S
authors.lastname: Jelovcan
authors.forename: Vera
authors.initials: V
authors.lastname: Buerger
authors.forename: Erich
authors.initials: E
authors.lastname: Tauber
authors.forename: Juergen
authors.initials: J
authors.lastname: Frisch
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
mesh_terms: D000328:Adult; D000368:Aged; D016516:CD4-CD8 Ratio; D049109:Cell Proliferation; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000276:immunology / Q000628:therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D016896:Treatment Outcome; D014611:Vaccination / Q000379:methods*; D022223:Vaccines, Subunit; D014765:Viral Vaccines / Q000627:therapeutic use*
chemical_list: D012367:RNA, Viral; D022223:Vaccines, Subunit; D014765:Viral Vaccines