A poxvirus vaccine is safe, induces T-cell responses, and decreases viral load in patients with chronic hepatitis C
F Habersetzer, G Honnet, C Bain, M Maynard–Muet… - Gastroenterology, 2011 - Elsevier
F Habersetzer, G Honnet, C Bain, M Maynard–Muet, V Leroy, JP Zarski, C Feray…
Gastroenterology, 2011•ElsevierBACKGROUND & 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 …
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 …
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 106, 107, or 108 plaque-forming units of TG4040 on study days 1, 8, and 15. Six additional patients were given the highest dose of vaccine (108 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 log10 to −1.24 log10, 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.
Elsevier
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