Perspectives for a vaccine against hepatitis C virus.

There is no vaccine for HCV and the only available treatment, IFNalpha alone or in combination with ribavirin, has proven efficacious in less than 50% of patients. Given that approximately 200 million chronic HCV infections have been estimated worldwide, there is a pressing need to develop vaccination strategies aimed at preventing and possibly eradicating HCV infection. However, several major practical and scientific problems arise in designing an HCV vaccine. First, HCV is only readily detected as RNA by PCR. Second, the only species that can be infected by HCV are humans and chimpanzees. Third, the virus does not replicate efficiently in vitro. Fourth, some viral proteins have very high mutability. Last, there is little information on correlates of immunity. Although an ideal vaccine should protect from infection, in that it should elicit sterilizing immunity, this is quite an ambitious goal in the PCR era. In the case of HCV, where acute HCV infection is a very limited health problem and infection can only be assessed by PCR, a more realistic goal might be to look for vaccines capable of protecting from chronic infection. We have preliminary evidence in chimpanzees that an HCV vaccine consisting of recombinant envelope proteins can elicit antibodies and inflammatory CD4+ T cell responses which can prevent chronic infection in the majority of vaccinees. Although the scientific and clinical challenges that need to be addressed are still substantial, advances in recombinant protein technology, novel adjuvants, and DNA vaccines, will be key in developing strategies to generate protective immunity against chronic HCV infection.