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

• Published in: Hepatology (Baltimore, Md.) Vol. 37; no. 1; pp. 52 - 59
• Main Authors: Qiao, Ming, Murata, Kazumoto, Davis, Anthony R., Jeong, Sook-Hyang, Liang, T.Jake
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA Elsevier Inc 2003; W.B. Saunders; Wiley
• Subjects: Adjuvants, Immunologic - pharmacology; Animals; Antibody Formation; Antigen Presentation; Biological and medical sciences; CD8-Positive T-Lymphocytes - immunology; Cytokines - immunology; Epidemiology. Vaccinations; General aspects; Hepacivirus - immunology; Hepatitis C, Chronic - immunology; Hepatitis C, Chronic - prevention & control; HLA-A2 Antigen - genetics; Infectious diseases; Lipid A - analogs & derivatives; Lipid A - pharmacology; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Transgenic; Saponins - pharmacology; T-Lymphocytes, Cytotoxic - immunology; Th1 Cells - immunology; Viral Hepatitis Vaccines - immunology; Virion - immunology; Immune response; Virus like particle; Rodentia; Transgenic animal; Hepatic disease; Experimental study; Infection; Immunoprophylaxis; Vertebrata; Mammalia; Mouse; Viral disease; Immunological adjuvant; Digestive diseases; Biological effect; Viral hepatitis C
• ISSN: 0270-9139; 1527-3350
• 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)-γ and interleukin (IL)-4 and intracellular cytokine staining of IFN-γ 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. (H EPATOLOGY 2003;37:52-59.)