Development of prophylactic and therapeutic vaccines against hepatitis C virus.

The hepatitis C virus was discovered 15 years ago as the agent responsible for most cases of transfusion-associated hepatitis non-A, non-B. At present, 180 million people worldwide are estimated to be infected with the virus, producing severe and progressive liver disease in millions and representing the most common reason for liver transplantation in adults. Although the spread of the virus can be halted by the application of primary prevention strategies, such as routine testing of blood donations, inactivation of blood products and systematic use of disposable needles and syringes, the development of a prophylactic vaccine could facilitate the control of this infection and protect those at high risk of being infected with hepatitis C virus. As the present therapy of chronic hepatitis C virus infections, consisting of a combined administration of pegylated interferon-alpha and ribavirin, is only successful in 50% of patients infected with genotype 1, and is costly and associated with serious side effects, there is an urgent need for better tolerated and more effective treatment modalities, and a therapeutic vaccine may be the solution. This review first provides an overview of the present knowledge regarding the interaction between the virus and immune system of the infected host, with special attention given to the possible mechanisms responsible for chronic evolution of the infection. The numerous candidate vaccines that have been developed in the past 10 years are discussed, including the studies in which their immunogenicity has been examined in rodents and chimpanzees. Finally, the only studies of therapeutic vaccines performed in humans to date are considered.