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

Vector Vaccines

The use of viral vectors for the delivery of HCV RNA is an appealing vaccine choice. Adenoviral vectors have shown to be potent inducers of HCV-specific T-cell responses in the chimpanzee model and to reduce peak HCV viremia during primary infection.[62] This approach may induce a broader range of viral epitopes than a peptide-based approach since the immunogen contained within the vaccine is not HLA restricted.

Modified vaccinia Ankara (MVA) is a highly attenuated poxvirus strain that has been used safely in several vaccine designs for conditions such as HIV, colorectal cancer, TB and melanoma. A therapeutic vaccine (TG4040) using MVA that expresses NS3/4/5B proteins has been evaluated for safety and immunogenicity in an open-label, multicenter, dose-escalation study (Table 4). Preliminary results were presented at the European Association for the Study of Liver Disease conference in 2009.[107] A total of 15 chronically infected HCV patients received three weekly injections, nine of whom received a fourth injection at 6 months. In six out of 15 patients, a decline in HCV viral load (0.5–1.4 log10) was observed in association with a significant CD8+ T-cell response. A Phase II trial using the vaccine in combination with standard treatment is planned.[203]

Adenovirus vectors are also being employed in a Phase I vaccine trial to deliver NS HCV proteins (NS3–5B) to 36 healthy volunteers.[204] The vaccine vectors are genetically modified so that they are unable to replicate and the polymerase activity of the NS proteins is inactivated to further enhance vaccine safety. To overcome the problem of pre-existing anti-adenoviral antibodies, which may limit vector efficacy, two adenoviral vectors to which humans are rarely exposed are used: Ad6 and a simian vector AdCh3. Early data from this trial were presented at the American Association for the Study of Liver Disease in 2009 where this approach was reported to be highly immunogenic in healthy volunteers following a single priming injection (Ad6).[73] Further studies are planned in HCV-infected patients.


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