title: Hepatitis C virus-like particles combined with novel adjuvant systems enhance virus-specific immune responses.
abstract: 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.
authors.affiliation: Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Qiao
authors.forename: Kazumoto
authors.initials: K
authors.lastname: Murata
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Davis
authors.forename: Sook-Hyang
authors.initials: SH
authors.lastname: Jeong
authors.forename: T Jake
authors.initials: TJ
authors.lastname: Liang
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000917:Antibody Formation; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D015789:HLA-A2 Antigen / Q000235:genetics; D016174:Hepacivirus / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000276:immunology / Q000517:prevention & control*; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012503:Saponins / Q000494:pharmacology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D014761:Viral Hepatitis Vaccines / Q000276:immunology*; D014771:Virion / Q000276:immunology
chemical_list: C000616023:AS01B adjuvant; D000276:Adjuvants, Immunologic; D016207:Cytokines; D015789:HLA-A2 Antigen; D008050:Lipid A; D012503:Saponins; D014761:Viral Hepatitis Vaccines; C078785:saponin QA-21V1; C048436:monophosphoryl lipid A