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Assessment of primary responses and induction of memory in primates infected with HCV and vaccinated with a candidate HCV vaccine

The HCV NS345Core polyprotein candidate vaccine was formulated in ISCOMATRIX?, a saponin based adjuvant, which has been demonstrated to promote antibody responses and induce T helper cell as well as cytotoxic T lymphocyte responses . Five chimpanzees received a 1 mg intramuscular dose of HCV Polyprotein in ISCOMATRIX? vaccine at 0, 1, 2, and 5 months before being challenged 6 months after the last dose with 100 CID50 of an heterologous HCV1a strain (HCV-H).

While the results from this study demonstrated the ability of the ISCOMATRIX? formulation of the NS345Core polyprotein to elicit HCV-specific CD4 and CD8 T cell responses, they also showed that these responses were not sufficient to confer protective immunity from infection with an heterologous HCV strain. In fact, while 40% of control animals cleared the virus, 80% of the polyprotein-vaccinated chimps developed chronic infection after a single intravenous challenge with HCV-H, as demonstrated by persistent HCV-RNA positive PCR results and slight, but consistent, increased ALT levels .

Nevertheless, evidence of antiviral activity was found in all vaccinated chimpanzees, which showed lower viremia and ALT levels in comparison to infected control animals, during the acute phase of infection. Since a broad CD4 and CD8 T cell response have been associated with a benign course of infection and higher number of HCV Core specific CTL’s have been found to correlate with an improved response to treatment with pegylated Interferon-alpha an Ribavirin (4-6) the results of the present study encourage the exploitation of HCV-polyprotein ISCOMATRIX? as a possible therapeutic vaccine, at least for those HCV chronic patients showing low or no response to current therapies.

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