Priming of CD4+ and CD8+ T cell responses using a HCV core ISCOMATRIX vaccine: a phase I study in healthy volunteers.

The disease burden and public health impact of chronic HCV infection continues to be a major problem globally. Current treatment for chronic HCV infection is not effective in all patients and is frequently associated with unacceptable side effects. Clearly a need exists for improved treatments and one such strategy is the use of therapeutic vaccines. Although still not completely understood, emerging data indicate that the generation of CD4(+) and CD8(+) T cells are important for the clearance of HCV. We have developed a prototype vaccine with the HCV Core protein and ISCOMATRIX (TM) adjuvant (HCV Core ISCOMATRIX (TM) vaccine). ISCOMATRIX (TM) vaccines have been shown to induce CD4+ and CD8+ T cell responses to a range of antigens in both animal models and in human studies. Additionally, ISCOMATRIX (TM) vaccines have been shown to be safe and generally well tolerated in several clinical trials. Preliminary studies demonstrated that the prototype HCV Core ISCOMATRIX (TM) vaccine induced strong CD4+ and CD8+ T cell responses in monkeys following immunization. Here we show the results of a Phase I placebo controlled, dose escalation clinical study designed to evaluate the safety, tolerability and immunogenicity of the HCV Core ISCOMATRIX (TM) vaccine in healthy individuals. The 30 subjects received three immunizations of HCV Core ISCOMATRIX (TM) vaccines or placebo vaccine on days 0, 28 and 56. The HCV Core ISCOMATRIX (TM) vaccines contained 5, 20 or 50 mu g HCV Core protein with 120 mu g ISCOMATRIX (TM) adjuvant. The adverse events reported were generally mild to moderate in severity, of short duration and self-limiting. The most common adverse events were injection site reactions such as pain and redness as well as myalgia. Antibody responses were detected in all but one of the participants receiving the HCV Core ISCOMATRIX (TM) vaccine and there was no indication of a dose response. CD8(+) T cell responses were only detected in two of the eight participants receiving the highest dose. T cell cytokines were detected in 7 of the 8 participants in the highest dose group. The results of this study support the further evaluation of this prototype HCV Core ISCOMATRIX (TM) vaccine in HCV infected subjects.