Grant: CIHR/Regional Partnership Program/Operating Grants

Hepatitis C virus is one of the viruses that cause liver disease. An estimated 170 million people are infected with hepatitis C virus, which amounts to ~3% of the world population. Although acute infection is often insidious, ~80% of infected people remain chronic carriers. The persistent infection eventually results in either mild chronic hepatitis or extensive liver damage. Treatment with interferon-alpha and ribavirin is effective in some chronic hepatitis C patients, but 40-50% of patients do not respond, and the drugs are expensive and associated with severe side effects, so the development of alternative treatments and vaccines is critical. Amongst al the immune cells involved, dendritic cells are critical for the development of immune responses to infectious agents and to vaccination. However, there is evidence that the dendritic cells of chronic hepatitis C patients are functionally impaired. Since this may make it difficult to induce an immune response to the virus or a vaccine in the patients in vivo, we plan to isolate the dendritic cells from the blood of healthy and hepatitis C virus-infected individuals, and compare their functional properties. This will then allow us to select stimuli to effectively activate the hepatitis C patients' dendritic cells. These activated dendritic cells can then be loaded with hepatitis C antigens and used as delivery vehicle for a therapeutic vaccine against chronic hepatitis C. Such therapy would circumvent the impaired dendritic cell function of chronic hepatitis C patients in vivo by giving necessary maturation stimuli ex vivo. Even if, as others suggest, hepatitis C virus does not affect dendritic cell function, dendritic cell-based vaccines induce very strong cell-mediated immune responses and thus are expected to be promising as a therapeutic in chronic hepatitis C patients, and also as a prophylactic for high-risk populations.