Grant: Operating Grant - Health Canada/CIHR Research Initiative on Hepatitis C

Hepatitis C virus (HCV) is the etiological agent of non-A, non-B hepatitis. An estimated 170 million people are infected with HCV, which amounts to 1-3% 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 HCV patients, but 40-50% of patients do not respond, so the development of alternative treatments and vaccines is critical. The induction of cellular immunity is thought to be critical for both preventive and therapeutic hepatitis C vaccines. Dendritic cells (DCs) are pivotal in the development of immune responses to infectious agents, and very suitable as vehicles for antigens in immunotherapy. Although the evidence is not consistent, the maturation and function of DCs may be impaired during persistent HCV infection. By evaluating functional and gene expression profiles of HCV-infected DCs and DCs from chronic HCV patients we intend to gain insight into the interactions between HCV and human DCs. This will allow us to select stimuli to effectively mature DCs from chronic HCV patients, which can then be used for DC therapy. Since DC maturation and function are modulated by the microenvironment, which may be different and not optimal in CHC patients in vivo, we expect DC therapy to be effective against chronic hepatitis C. DC therapy would circumvent the diminished and down-regulated DC function of chronic HCV patients in vivo by giving necessary maturation stimuli ex vivo. Even if as others suggest, HCV does not affect DC function, DC-based vaccines are highly effective inducers of cell-mediated immune responses and thus are expected to be promising not only as a therapeutic for chronic HCV patients, but also as a prophylactic for high-risk populations.