The Need for a Therapeutic HCV Vaccine
Current gold-standard therapy for HCV infection is weekly subcutaneous injections of pegylated interferon (PEG-IFN) combined with daily oral ribavirin for a period of 24 weeks for genotypes 2 and 3, and 48 weeks for genotypes 1 and 4. Therapy is fraught with significant side effects and leads to a sustained virological response (SVR; patients are negative for the virus by reverse transcription PCR 6 months after finishing therapy) in approximately 40–50% of patients with genotype 1 infection, 65–70% with genotype 3 and 80% of those with genotype 2. PEG-IFN and ribavirin treatment is also expensive and, at an average cost of approximately GB£7000 in the UK for a treatment course, is unaffordable in developing countries.
Two viral protease inhibitors (telaprevir and boceprevir) are currently in Phase III clinical trials for HCV and more are in development. These drugs will need concomitant PEG-IFN/ribavirin therapy to avoid the rapid emergence of viral mutants and are currently only effective against genotype 1 infection. It is expected they will increase SVR rates following treatment to 70%.[17,18] Because these drugs will be used together with PEG-IFN/ribavirin, the cost of treatment will rise further and additional side effects, in particular skin rashes, can be anticipated. The cost of a 3-month course of protease inhibitor in the UK is currently predicted to be GB£18,000–22,000 [Vertex Pharmaceuticals, Pers. Comm.]. Many other direct antiviral therapies are in development but these are unlikely to reach clinical application in the next few years.
Interestingly, the SVR rate of individuals that are treated in the early phase of infection with IFN alone is very high (70–90%). The reasons for this are not known but may relate to the fact that the infecting virus has not yet evolved to subvert the effects of IFN – or alternatively, that IFN therapy harnesses the host's robust natural immunity that is present in acute infection in a way that it is unable to do so once chronic infection is established. Similarly, it is plausible that a therapeutic vaccination strategy may prove more efficacious in early infection. In clinical practice, however, acute infection is frequently asymptomatic and patients usually do not present to clinicians until chronic infection is established.
Clearly, a therapeutic vaccine that increases SVR rates in chronic infection, or reduces the duration of therapy would represent a major step forward.
Expert Rev Vaccines. 2011;10(5):659-672. © 2011 Expert Reviews Ltd.
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