A potential vaccine candidate against chronic hepatitis C (HCV) infections is presented in a thesis from Karolinska Institutet. The new genetic vaccine can activate immune responses that are needed to clear HCV, a disease that today is difficult to treat effectively.
The hepatitis C virus (HCV) is a major cause of chronic liver disease worldwide. It is estimated that HCV affects approximately 170 million people around the world. Today, no vaccine is available to prevent or cure HCV infections. Antiviral therapy is used quite effectively, but in 60-80 per cent of the patients become chronic carriers of the virus in their liver. One feature of HCV infection is the high rate of viral persistence. The mechanism of viral persistence is largely unknown, although the high genetic variability is thought to play a key role.
In Lars Frelin’s thesis the HCV NS3 protein is studied in detail since it performs key functions in the viral life cycle. These are unwinding and strand separation of the viral RNA and proteolytic processing of the precursor polyprotein. To obtain the complete protease the NS4A co-factor was included in the NS3-based vaccines. NS4A has been shown to enhance the stability of NS3 and to target the NS3/4A complex to intracellular membranes. The latter is most likely of importance for the formation of the replication complex. Also, the NS3 region has a limited genetic variability and several studies have now demonstrated that NS3-specific CD4+ and CD8+ T-cell responses are crucial for the resolution of HCV infections. Thus, several factors suggest that the NS3 region should be well suited for vaccine development.
Ulla Bredberg-Radén | alfa
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