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.