Characterization of hepatitis C virus core-specific immune responses primed in rhesus macaques by a nonclassical ISCOM vaccine

J Immunol. 2001 Mar 1;166(5):3589-98. doi: 10.4049/jimmunol.166.5.3589.

Abstract

Current therapies for the treatment of hepatitis C virus (HCV) infection are only effective in a restricted number of patients. Cellular immune responses, particularly those mediated by CD8(+) CTLs, are thought to play a role in the control of infection and the response to antiviral therapies. Because the Core protein is the most conserved HCV protein among genotypes, we evaluated the ability of a Core prototype vaccine to prime cellular immune responses in rhesus macaques. Since there are serious concerns about using a genetic vaccine encoding for Core, this vaccine was a nonclassical ISCOM formulation in which the Core protein was adsorbed onto (not entrapped within) the ISCOMATRIX, resulting in approximately 1-microm particulates (as opposed to 40 nm for classical ISCOM formulations). We report that this Core-ISCOM prototype vaccine primed strong CD4(+) and CD8(+) T cell responses. Using intracellular staining for cytokines, we show that in immunized animals 0.30-0.71 and 0.32-2.21% of the circulating CD8(+) and CD4(+) T cells, respectively, were specific for naturally processed HCV Core peptides. Furthermore, this vaccine elicited a Th0-type response and induced a high titer of Abs against Core and long-lived cellular immune responses. Finally, we provide evidence that Core-ISCOM could serve as an adjuvant for the HCV envelope protein E1E2. Thus, these data provide evidence that Core-ISCOM is effective at inducing cellular and humoral immune responses in nonhuman primates.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Alleles
  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Survival / immunology
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • Genes, MHC Class I / immunology
  • Hepacivirus / genetics
  • Hepacivirus / immunology*
  • Hepatitis Antibodies / biosynthesis
  • ISCOMs / administration & dosage
  • ISCOMs / immunology*
  • Immunity, Cellular / immunology
  • Immunization Schedule
  • Injections, Intradermal
  • Injections, Intramuscular
  • Lymphocyte Activation
  • Macaca mulatta / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Solubility
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Cytotoxic / cytology
  • T-Lymphocytes, Cytotoxic / immunology
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / immunology
  • Viral Core Proteins / administration & dosage
  • Viral Core Proteins / genetics
  • Viral Core Proteins / immunology*
  • Viral Envelope Proteins / administration & dosage
  • Viral Envelope Proteins / immunology
  • Viral Hepatitis Vaccines / administration & dosage
  • Viral Hepatitis Vaccines / genetics
  • Viral Hepatitis Vaccines / immunology*

Substances

  • Adjuvants, Immunologic
  • E1 protein, Hepatitis C virus
  • Epitopes, T-Lymphocyte
  • Hepatitis Antibodies
  • ISCOMs
  • Vaccines, Synthetic
  • Viral Core Proteins
  • Viral Envelope Proteins
  • Viral Hepatitis Vaccines
  • nucleocapsid protein, Hepatitis C virus
  • glycoprotein E2, Hepatitis C virus