Hepatitis C virus-like particles combined with novel adjuvant systems enhance virus-specific immune responses

Hepatology. 2003 Jan;37(1):52-9. doi: 10.1053/jhep.2003.50000.


We have previously described the generation of hepatitis C virus-like particles (HCV-LPs) in insect cells and shown that immunization with HCV-LPs elicited both humoral and cellular immune responses in mice. To further characterize the HCV-LPs as a vaccine candidate, we evaluated the effects of adjuvant AS01B (monophosphoryl lipid A [MPL] and QS21), CpG 10105, and the combination of the 2 adjuvants on the immunogenicity of HCV-LPs in AAD mice (transgenic for HLA-A2.1). All HCV-LP-immunized mice (with or without adjuvant) developed high titers of anti-HCV E1/E2 antibodies after 4 injections intramuscularly. However, antibody titers in mice immunized with HCV-LP plus AS01B, plus CpG 10105, or plus the combination of AS01B and CpG 10105 were 4, 3, and 10 times higher, respectively, than that of HCV-LP alone. Isotype analysis of the induced anti-envelope antibodies showed that HCV-LP alone induced a predominant immunoglobulin (Ig) G1 response. In contrast, when the 2 adjuvants AS01B and CpG 10105 were combined, the response became predominantly IgG2a whereas HCV-LP plus AS01B or CpG 10105 gave a mixed IgG1 and IgG2a response, indicating that AS01B and CpG 10105 promote a more T-helper type 1 (Th1) response and that combining the 2 adjuvants results in an additive or synergistic interaction. These observations were further confirmed by the results of CD4(+) enzyme-linked immunospot assay for interferon (IFN)-gamma and interleukin (IL)-4 and intracellular cytokine staining of IFN-gamma producing CD8(+) cells. In conclusion, HCV-LP is a promising vaccine candidate against HCV infection and the adjuvants used are potent immune enhancers for this approach.

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Animals
  • Antibody Formation
  • Antigen Presentation
  • CD8-Positive T-Lymphocytes / immunology
  • Cytokines / immunology
  • HLA-A2 Antigen / genetics
  • Hepacivirus / immunology*
  • Hepatitis C, Chronic / immunology
  • Hepatitis C, Chronic / prevention & control*
  • Lipid A / analogs & derivatives*
  • Lipid A / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Saponins / pharmacology*
  • T-Lymphocytes, Cytotoxic / immunology
  • Th1 Cells / immunology
  • Viral Hepatitis Vaccines / immunology*
  • Virion / immunology


  • AS01B adjuvant
  • Adjuvants, Immunologic
  • Cytokines
  • HLA-A2 Antigen
  • Lipid A
  • Saponins
  • Viral Hepatitis Vaccines
  • saponin QA-21V1
  • monophosphoryl lipid A