Safety and immunogenicity of HCV E1E2 vaccine adjuvanted with MF59 administered to healthy adults

Vaccine. 2010 Aug 31;28(38):6367-73. doi: 10.1016/j.vaccine.2010.06.084. Epub 2010 Jul 7.

Abstract

Background: Hepatitis C virus (HCV) causes chronic liver disease that often leads to cirrhosis and hepatocellular carcinoma. In animal studies, chimpanzees were protected against chronic infection following experimental challenge with either homologous or heterologous HCV genotype 1a strains which predominate in the USA and Canada. We describe the first in humans clinical trial of this prophylactic HCV vaccine.

Methods: HCV E1E2 adjuvanted with MF59C.1 (an oil-in-water emulsion) was given at 3 different dosages on day 0 and weeks 4, 24 and 48 in a phase 1, placebo-controlled, dose escalation trial to healthy HCV-negative adults.

Results: There was no significant difference in the proportion of subjects reporting adverse events across the groups. Following vaccination subjects developed antibodies detectable by ELISA, CD81 neutralization and VSV/HCV pseudotype neutralization. There were no significant differences between vaccine groups in the number of responders and geometric mean titers for each of the three assays. All subjects developed lymphocyte proliferation responses to E1E2 and an inverse response to increasing amounts of antigen was noted.

Conclusions: The vaccine was safe and generally well-tolerated at each of the 3 dosage levels and induced antibody and lymphoproliferative responses. A larger study to further evaluate safety and immunogenicity is warranted.

Trial registration: ClinicalTrials.gov NCT00500747.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Adult
  • Antibodies, Neutralizing / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Proliferation
  • Double-Blind Method
  • Female
  • Hepacivirus / immunology*
  • Hepatitis Antibodies / blood
  • Hepatitis C / immunology
  • Hepatitis C / prevention & control*
  • Humans
  • Immunization Schedule
  • Male
  • Middle Aged
  • Polysorbates / administration & dosage*
  • Squalene / administration & dosage*
  • Viral Hepatitis Vaccines / administration & dosage
  • Viral Hepatitis Vaccines / adverse effects
  • Viral Hepatitis Vaccines / immunology*
  • Young Adult

Substances

  • Adjuvants, Immunologic
  • Antibodies, Neutralizing
  • Hepatitis Antibodies
  • MF59 oil emulsion
  • Polysorbates
  • Viral Hepatitis Vaccines
  • Squalene

Associated data

  • ClinicalTrials.gov/NCT00500747