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 adjuvant (HCV Core ISCOMATRIX vaccine). ISCOMATRIX 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 vaccines have been shown to be safe and generally well tolerated in several clinical trials. Preliminary studies demonstrated that the prototype HCV Core ISCOMATRIX 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 vaccine in healthy individuals. The 30 subjects received three immunizations of HCV Core ISCOMATRIX vaccines or placebo vaccine on days 0, 28 and 56. The HCV Core ISCOMATRIX vaccines contained 5, 20 or 50 microg HCV Core protein with 120 mug ISCOMATRIX 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 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 vaccine in HCV infected subjects.

Immunogenicity of a reduced dose of A/H3N2 in the 2005 southern hemisphere formulation of inactivated split influenza vaccine.

BACKGROUND: The 2005 southern hemisphere formulation of the inactivated split-virion influenza vaccine Vaxigrip unintentionally contained a lower concentration of haemagglutinin (HA) than European Pharmacopoeia (EP) and WHO specifications for one of the three strains. OBJECTIVES: To evaluate the immunogenicity of the 2005 southern hemisphere formulation of an influenza vaccine containing 9 microg/dose of HA for A/Wellington/1/2004(H3N2) strain, and 15 microg/dose for each of the A/New Caledonia/20/99(H1N1) strain and B/Shanghai/361/2002-like strains. PATIENTS/METHODS: In an open, non-controlled multicentre clinical trial, 75 healthy adults (18-59 years) and 65 healthy older adults (> or =60 years) were vaccinated once. Serum samples were obtained on D0 and 21 for haemagglutination inhibition (HAI) antibody titration. RESULTS: A high proportion of adults (64%) and elderly (68%) were already seroprotected (HAI titre of > or =40) against A/Wellington/1/2004(H3N2) before vaccination, probably due to high circulation of an antigenically similar H3N2 strain and a high 2004 vaccination rate. By D21, seroprotection rates against H3N2 attained 93.8% and 96.0% in adults and elderly respectively. The other two immunogenicity criteria for annual licensure of influenza vaccines in Europe were also met in both age groups for the H3N2 strain, and also for the H1N1 and B strains. CONCLUSIONS: These results enabled the 2005 southern hemisphere vaccine to be used in expectation that it would provide satisfactory protection against influenza, despite the reduced H3N2 antigen content.