The challenge of developing a vaccine against hepatitis C virus.

Hepatitis C virus (HCV) is a single stranded positivesense RNA virus belonging to the Flaviviridae family [1]. Members of this family are small enveloped viruses that have been classified into three different genera: Pestivirus, which contains animal pathogens such as bovine viral diarrhea virus and hog cholera virus; Flavirirus, which contains mostly arthropod-transmitted human pathogens such as dengue fever and yellow fever viruses; and Hepacivirus, whose only member is HCV [1]. The recently discovered GB virus-B (GBV-B), which causes hepatitis in experimentally infected tamarins, will probably be classified with HCV [2,3]. HCV is an important human pathogen, but the scope of its impact on human health has only recently been truly appreciated. The prevalence of HCV infection in the general population varies depending on the geographical area and ranges from less than 1% in Northern Europe to as high as 20% in some developing countries such as Egypt. It has been estimated that approximately 170 million people are chronically infected with HCV worldwide [4]. However, despite effective screening of blood and blood products, and use of sterile techniques, acute HCV is still a problem in industrialized countries. For example, around 40 000 new HCV infections occur each year in the US [5] and the majority of individuals with acute infection become persistently infected [6]. The source of these infections is principally the illicit use of parenteral drugs. Exposure to contaminated blood, especially via contaminated needles, syringes and surgical instruments, also accounts for the spread of HCV in developing countries. Chronic HCV infection is an important cause of liver cirrhosis and hepatocellular carcinoma in the Western World and Japan and, furthermore, represents the most frequent indication for liver transplantation in developed countries. Treatment of chronic HCV infection has improved considerably during the last few years: the combination of interferon and the nucleoside analogue ribavirin achieves a sustained virological response in approximately 40% of patients with chronic hepatitis C [7–9]. It is possible that during the next few years, new antiviral agents such as inhibitors of the viral protease, helicase or polymerase will further improve the response rate of the current therapeutic agents. However, antiviral therapy is not affordable in most developing countries, where the prevalence of HCV is generally the highest. Thus, given the huge reservoir of HCV worldwide, the development of an effective vaccine will be the only way to control disease associated with HCV infection.