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Chiron Corp., Emeryville, CA 94608; and
CSL Ltd., Parkville, Victoria, Australia
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 
1-µm
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.
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