Hepatitis C

Hepatitis C virus (HCV) is a major public health problem, with over 180 million persons infected worldwide and at risk for developing cirrhosis or liver cancer. Current interferon-based treatment options are expensive, often associated with considerable toxicity, and moreover are of limited efficacy. Thus, vaccines capable of either preventing new infections or exerting a therapeutic effect on established infections would be of value. Both types of vaccines remain elusive goals, however, in part because immunity against the virus is very poorly understood. An impressive degree of genetic (and likely antigenic) variation among HCV strains is another barrier to vaccine development. In addition, there are no readily available animal models of hepatitis C, which greatly complicates vaccine development. Protective immunity has been correlated mainly with virus-specific CD4+ and CD8+ T-cell responses, while the role played by antibodies to the virus is less clear but still potentially important. Immunization with recombinant viral envelope proteins induces primarily antibody and CD4+ Th-cell responses. While not preventing acute infection, such a vaccine may have prevented persistent infection in chimpanzees challenged with a virus closely related to the vaccine strain. Other vaccine strategies that have been explored include the use of synthetic peptides, genetic immunization, recombinant vectors, virus-like particles, or combinations of these. While many of these approaches have induced CD8+ T-cell responses, as well as CD4+ Th and B-cell responses, few have shown clear evidence of providing protective immunity against HCV challenge. Other efforts have focused on ex vivo stimulation of dendritic cells, and passive immunization with polyclonal and monoclonal antibodies. This chapter summarizes what is known of the immune responses that control HCV infection and different strategies that have been pursued for HCV vaccine development, and outlines the current status of vaccine candidates in pre-clinical and clinical development.