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

Authors

  • Ming Qiao,

    1. Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD
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  • Kazumoto Murata,

    1. Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD
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  • Anthony R. Davis,

    1. Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD
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  • Sook-Hyang Jeong,

    1. Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD
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  • T. Jake Liang M.D.

    Corresponding author
    1. Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD
    • Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 10 Center Dr., Room 9B16, Bethesda, MD 20892-1800. Fax: 301-402-0491
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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)-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.

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