Vaccination for Hepatitis C Virus

Closing in on an Evasive Target

John Halliday; Paul Klenerman; Eleanor Barnes


Expert Rev Vaccines. 2011;10(5):659-672. 

In This Article

Abstract and Introduction


Hepatitis C virus (HCV) infects more than 170 million people globally and is a leading cause of liver cirrhosis, transplantation and hepatocellular carcinoma. Current gold-standard therapy often fails, has significant side effects in many cases and is expensive. No vaccine is currently available. The fact that a significant proportion of infected people spontaneously control HCV infection in the setting of an appropriate immune response suggests that a vaccine for HCV is a realistic goal. A comparative analysis of infected people with distinct clinical outcomes has enabled the characterization of many important innate and adaptive immune processes associated with viral control. It is clear that a successful HCV vaccine will need to exploit and enhance these natural immune defense mechanisms. New HCV vaccine approaches, including peptide, recombinant protein, DNA and vector-based vaccines, have recently reached Phase I/II human clinical trials. Some of these technologies have generated robust antiviral immunity in healthy volunteers and infected patients. The challenge now is to move forward into larger at-risk or infected populations to truly test efficacy.


Hepatitis C virus (HCV) infects more than 170 million people globally with another 3 million people newly infected each year.[1,2] Following acute infection, 20% of people eradicate the virus over weeks or months and are often asymptomatic. The remaining 80% of people will develop chronic disease, of whom approximately 20% will eventually develop liver cirrhosis and 1–5% will develop liver cancer.[3–5] HCV infection is now the leading cause for liver transplantation in the Western world. Disease prevalence varies by region, with the highest rates in parts of Asia and Africa where up to 20% of the population are infected.[6] The current treatment for HCV is pegylated interferon and ribavirin. This is expensive, prolonged, has an extensive side-effect profile and frequently fails. Clearly then, there is a real need for both a prophylactic vaccine that will prevent or attenuate primary infection, and also a therapeutic HCV vaccine that will increase cure rates of infected patients, and substantial progress has been made in this endeavor in recent years.

This article will first detail our current understanding of HCV infection, pathogenesis and treatment, and highlight the significant degree of viral diversity that presents a real challenge to vaccine development. Next we will review host–viral immune interactions and the broader challenges to the successful development of a vaccine. Finally, we will examine vaccine approaches that have reached human clinical trials and present our vision of this rapidly moving field for the future.


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