Sustained viral load reduction in treatment-naive HCV genotype 1 infected patients after therapeutic peptide vaccination

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• 作者：Christoph S. Klade^b ; Elisabeth Schuller^b ; ^{elisabeth.schuller@almirall.com} ; Thomas Boehm^b ; Alexander von Gabain^b ; Michael P. Manns^a
• 关键词：IC41 peptide vaccine ; Therapeutic HCV vaccination
• 刊名：Vaccine
• 出版年：2012
• 期刊代码：89_0264410x
• 类别：imm
• 出版时间：19 April, 2012
• 卷：30
• 期：19
• 页码：2943-2950
• 文件大小：875 K

摘要

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-na茂ve 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 脳 10⁶ 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.