title: Sustained viral load reduction in treatment-naive HCV genotype 1 infected patients after therapeutic peptide vaccination.
abstract: BACKGROUND
  Novel antivirals augment treatment efficacy in chronic HCV infection, to overcome limitations on safety profile alternative approaches are warranted. The effect of a therapeutic peptide vaccine on HCV viral load was investigated in treatment-naïve genotype 1 HCV patients.
  
  
  METHODS
  Fifty patients received 8 intradermal IC41 vaccinations biweekly with topical application of the TLR7 agonist imiquimod (Group A). In Group B, 21 patients received a condensed schedule of 16 subcutaneous vaccinations weekly without imiquimod.
  
  
  RESULTS
  At Week 16 Group A (n=44) showed a statistically significant (p=0.0013) HCV viral load decline of 0.21 log. 24 weeks after the last vaccination the viral load decreased by 0.47 log (p<0.0001) in 34 subjects. This effect was more pronounced in 17 patients with high baseline HCV (>2×10(6)IU/ml) with a 0.61 log decline, which was statistically significant (p<0.02) starting two weeks after the third vaccination. No apparent effect on HCV viral load was observed in Group B (n=21). In Group A eight patients (24%) showed a viral load response defined as a decline of >0.8 log. Overall, about 30-55% of patients showed T cell responses during the vaccination series and up to six months in both groups. No significant correlations between the HCV viral load decrease and T cell immune response were detected.
  
  
  CONCLUSIONS
  This is the first report on a significant antiviral effect of a peptide vaccine in HCV infected patients. Response kinetics with increased HCV RNA decline 24 weeks after the last IC41 vaccination is encouraging.
authors.affiliation: Intercell AG, Vienna Biocenter 3, A 1030 Vienna, Austria.
authors.forename: Christoph S
authors.initials: CS
authors.lastname: Klade
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Schuller
authors.forename: Thomas
authors.initials: T
authors.lastname: Boehm
authors.forename: Alexander
authors.initials: A
authors.lastname: von Gabain
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000293:Adolescent; D000328:Adult; D000634:Aminoquinolines / Q000008:administration & dosage; D000998:Antiviral Agents / Q000008:administration & dosage*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics; D006526:Hepatitis C / Q000628:therapy*; D006801:Humans; D000077271:Imiquimod; D007167:Immunotherapy / Q000379:methods*; D007271:Injections, Intradermal; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D016896:Treatment Outcome; D022223:Vaccines, Subunit / Q000008:administration & dosage; D014761:Viral Hepatitis Vaccines / Q000008:administration & dosage*; D019562:Viral Load; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D000998:Antiviral Agents; D012367:RNA, Viral; D022223:Vaccines, Subunit; D014761:Viral Hepatitis Vaccines; D000077271:Imiquimod