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

Article Authors:N K Polakos; D Drane; J Cox; P Ng; M J Selby; D Chien; D T O'Hagan; M Houghton; X Paliard
Article Title:Characterization of hepatitis C virus core-specific immune responses primed in rhesus macaques by a nonclassical ISCOM vaccine.
Reference Detail
Reference ID:1001939
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.
Affiliations:Chiron Corp., Emeryville, CA 94608, USA.
Reference Type:Literature
PubMed ID:11207320
Journal:J Immunol
Journal Volume:166
Article Pages:3589-98
Journal ISSN:0022-1767
Article Chemical List: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
Article MeSH List:Adjuvants, Immunologic(administration & dosage ); Alleles; Animals; CD4-Positive T-Lymphocytes(immunology; metabolism ); Cell Survival(immunology ); Epitopes, T-Lymphocyte(immunology ); Female; Genes, MHC Class I(immunology ); Hepacivirus(genetics; immunology ); Hepatitis Antibodies(biosynthesis ); ISCOMs(administration & dosage; immunology ); Immunity, Cellular(immunology ); Immunization Schedule; Injections, Intradermal; Injections, Intramuscular; Lymphocyte Activation; Macaca mulatta(immunology ); Mice; Mice, Inbred C57BL; Solubility; T-Lymphocyte Subsets(immunology; metabolism ); T-Lymphocytes, Cytotoxic(cytology; immunology ); Vaccines, Synthetic(administration & dosage; immunology ); Viral Core Proteins(administration & dosage; genetics; immunology ); Viral Envelope Proteins(administration & dosage; immunology ); Viral Hepatitis Vaccines(administration & dosage; genetics; immunology )
Curation Last Updated:2015-01-27 18:42:30