Characterization of hepatitis C virus core-specific immune responses primed in rhesus macaques by a nonclassical ISCOM vaccine.
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.
Polakos
N K
NK
Chiron Corp., Emeryville, CA 94608, USA.
Drane
D
D
Cox
J
J
Ng
P
P
Selby
M J
MJ
Chien
D
D
O'Hagan
D T
DT
Houghton
M
M
Paliard
X
X
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000483:Alleles; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002470:Cell Survival / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D005805:Genes, MHC Class I / Q000276:immunology; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D006508:Hepatitis Antibodies / Q000096:biosynthesis; D016882:ISCOMs / Q000008:administration & dosage / Q000276:immunology*; D007111:Immunity, Cellular / Q000276:immunology; D007115:Immunization Schedule; D007271:Injections, Intradermal; D007273:Injections, Intramuscular; D008213:Lymphocyte Activation; D008253:Macaca mulatta / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012995:Solubility; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D014758:Viral Core Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000008:administration & dosage / Q000276:immunology; D014761:Viral Hepatitis Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
D000276:Adjuvants, Immunologic; C087035:E1 protein, Hepatitis C virus; D018984:Epitopes, T-Lymphocyte; D006508:Hepatitis Antibodies; D016882:ISCOMs; D014614:Vaccines, Synthetic; D014758:Viral Core Proteins; D014759:Viral Envelope Proteins; D014761:Viral Hepatitis Vaccines; C069130:nucleocapsid protein, Hepatitis C virus; C091015:glycoprotein E2, Hepatitis C virus