A poxvirus vaccine is safe, induces T-cell responses, and decreases viral load in patients with chronic hepatitis C

Gastroenterology. 2011 Sep;141(3):890-899.e1-4. doi: 10.1053/j.gastro.2011.06.009. Epub 2011 Jun 13.

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00529321.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Viral / blood
  • Dose-Response Relationship, Drug
  • Female
  • Genotype
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / drug therapy
  • Hepatitis C, Chronic / pathology*
  • Hepatitis C, Chronic / virology*
  • Humans
  • Interferon-gamma / metabolism
  • Male
  • Middle Aged
  • Poxviridae / immunology*
  • RNA, Viral / blood
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology
  • Viral Load / drug effects*
  • Viral Nonstructural Proteins / immunology
  • Viral Vaccines / adverse effects
  • Viral Vaccines / pharmacology*
  • Viral Vaccines / therapeutic use

Substances

  • Antibodies, Viral
  • NS3 protein, hepatitis C virus
  • NS4 protein, hepatitis C virus
  • RNA, Viral
  • Viral Nonstructural Proteins
  • Viral Vaccines
  • Interferon-gamma
  • NS-5 protein, hepatitis C virus

Associated data

  • ClinicalTrials.gov/NCT00529321