Abstract
Clearance of infections caused by the hepatitis C virus (HCV) correlates with HCV-specific T cell function. We therefore evaluated therapeutic vaccination in 12 patients with chronic HCV infection. Eight patients also underwent a subsequent standard-of-care (SOC) therapy with pegylated interferon (IFN) and ribavirin. The phase I/IIa clinical trial was performed in treatment naive HCV genotype 1 patients, receiving four monthly vaccinations in the deltoid muscles with 167, 500, or 1,500 μg codon-optimized HCV nonstructural (NS) 3/4A-expressing DNA vaccine delivered by in vivo electroporation (EP). Enrollment was done with 2 weeks interval between patients for safety reasons. Treatment was safe and well tolerated. The vaccinations significantly improved IFN-γ-producing responses to HCV NS3 during the first 6 weeks of therapy. Five patients experienced 2-10 weeks 0.6-2.4 log10 reduction in serum HCV RNA. Six out of eight patients starting SOC therapy within 1-30 months after the last vaccine dose were cured. This first-in-man therapeutic HCV DNA vaccine study with the vaccine delivered by in vivo EP shows transient effects in patients with chronic HCV genotype 1 infection. The interesting result noted after SOC therapy suggests that therapeutic vaccination can be explored in a combination with SOC treatment.
Publication types
-
Clinical Trial
-
Clinical Trial, Phase I
-
Clinical Trial, Phase II
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adult
-
Antiviral Agents / administration & dosage
-
Antiviral Agents / adverse effects
-
Antiviral Agents / therapeutic use*
-
Combined Modality Therapy
-
Electroporation
-
Female
-
Hepacivirus / genetics
-
Hepacivirus / immunology
-
Hepacivirus / physiology
-
Hepatitis C, Chronic / genetics
-
Hepatitis C, Chronic / therapy*
-
Hepatitis C, Chronic / virology
-
Humans
-
Interferon-alpha / administration & dosage
-
Interferon-alpha / adverse effects
-
Interferon-alpha / therapeutic use*
-
Interferons
-
Interleukins / genetics
-
Lymphocyte Activation
-
Male
-
Middle Aged
-
Polyethylene Glycols / administration & dosage
-
Polyethylene Glycols / adverse effects
-
Polyethylene Glycols / therapeutic use*
-
RNA, Viral / blood
-
Recombinant Proteins / administration & dosage
-
Recombinant Proteins / adverse effects
-
Recombinant Proteins / therapeutic use
-
Ribavirin / administration & dosage
-
Ribavirin / adverse effects
-
Ribavirin / therapeutic use*
-
Standard of Care
-
T-Lymphocytes / immunology
-
Vaccines, DNA / administration & dosage
-
Vaccines, DNA / adverse effects
-
Vaccines, DNA / immunology
-
Vaccines, DNA / therapeutic use*
-
Viral Hepatitis Vaccines / administration & dosage
-
Viral Hepatitis Vaccines / adverse effects
-
Viral Hepatitis Vaccines / therapeutic use*
-
Viral Load
Substances
-
Antiviral Agents
-
interferon-lambda, human
-
Interferon-alpha
-
Interleukins
-
RNA, Viral
-
Recombinant Proteins
-
Vaccines, DNA
-
Viral Hepatitis Vaccines
-
Polyethylene Glycols
-
Ribavirin
-
Interferons
-
peginterferon alfa-2a