A Poxvirus Vaccine Is Safe, Induces T-Cell Responses, and Decreases Viral Load in Patients With Chronic Hepatitis C

作者：Habersetzer Francois; Honnet Geraldine; Bain Christine; Maynard Muet Marianne; Leroy Vincent; Zarski Jean Pierre; Feray Cyrille; Baumert Thomas F; Bronowicki Jean Pierre; Doffoel Michel; Trepo Christian; Agathon Delphine; Toh Myew Ling; Baudin Martine; Bonnefoy Jean Yves; Limacher Jean Marc; Inchauspe Genevieve^*

来源：Gastroenterology, 2011, 141(3): 890-U618.

DOI：10.1053/j.gastro.2011.06.009

• Therapeutic Vaccine
• Virology
• Liver Disease
• Immunity

BACKGROUND & AIMS: Therapy for chronic hepatitis C (CHC) has limited efficacy, adverse effects, and high costs. Cohort and vaccine-based preclinical studies have indicated the importance of T-cell-based immunity in controlling viral infection. TG4040 is a recombinant poxvirus vaccine that expresses the hepatitis C virus (HCV) proteins NS3, NS4, and NS5B. We performed a phase I clinical trial to assess the safety, immunogenicity, and early antiviral efficacy of TG4040 in patients with CHC. METHODS: In an open-label, dose-escalating study, patients with mild CHC (genotype 1) were assigned to 3 groups of 3 patients each; they received subcutaneous injections of 10(6), 10(7), or 10(8) plaque-forming units of TG4040 on study days 1, 8, and 15. Six additional patients were given the highest dose of vaccine (10(8) plaque-forming units). Patients were followed for 6 months after the last injection. T-cell-based and antibody responses and levels of HCV RNA were measured. RESULTS: All 3 doses of TG4040 were well tolerated, without serious adverse events. Vaccine-induced HCV-specific cellular immune responses were observed in 5 of the 15 patients (33%). A transient decrease in circulating levels of HCV RNA, from -0.52 log(10) to -1.24 log(10), was observed in 8 patients; in 5 patients, the lowest level of HCV RNA was observed on day 37, after the first injection. The most pronounced decrease in viral load occurred in 2 patients, who also had marked vaccine-induced T-cell responses. CONCLUSIONS: In patients with CHC, the viral-vector-based vaccine TG4040 had a good safety profile, induced HCV-specific cellular immune responses, and reduced viral load. This vaccine should be investigated in further clinical studies, in combination with standard of care.

• 出版日期2011-9