Hepatitis C virus-like particles induce virus-specific humoral and cellular immune responses in mice

Hepatology. 2001 Aug;34(2):417-23. doi: 10.1053/jhep.2001.26523.

Abstract

We have recently described the production of hepatitis C virus-like particles (HCV-LPs) in insect cells that resemble the putative virions. Here we evaluate the humoral and cellular immunogenicity of the virus-like particles with or without viral p7 protein, a small viral polypeptide that resides between the structural and nonstructural regions of the HCV polyprotein and whose function has not been defined. Immunized BALB/c mice developed high titers of anti-E2 antibodies and virus-specific cellular immune responses including cytotoxic T lymphocytes and T helper responses with gamma interferon production. The virus-like particles without p7 generated a higher cellular immune response with a more T(H)1 profile than the particles with p7. Immunization of heat-denatured particles resulted in substantially lower humoral and cellular responses, suggesting that the immunogenicity is strongly dependent on particle formation. Administration of CpG oligonucleotide or cationic lipid 3beta-[N-(N',N'-dimethylaminoethane)carbamoyl]cholesterol (DC-Chol), two potent adjuvants, did not significantly enhance the immunogenicity of HCV-LPs. Our results indicate that HCV-LPs can induce humoral and cellular immune responses and offer a promising approach to vaccine development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic
  • Animals
  • Antibody Formation
  • Cholesterol / analogs & derivatives
  • Cholesterol / immunology
  • Female
  • Hepacivirus / immunology*
  • Immunity, Cellular
  • Immunization
  • Mice
  • Mice, Inbred BALB C
  • Oligonucleotides / immunology
  • T-Lymphocytes, Cytotoxic / physiology
  • T-Lymphocytes, Helper-Inducer / physiology
  • Virion / immunology*

Substances

  • Adjuvants, Immunologic
  • Oligonucleotides
  • 3-(N-(N',N'-dimethylaminoethane)carbamoyl)cholesterol
  • Cholesterol