Therapeutic vaccines against hepatitis C virus

Hepatitis C virus (HCV) is a blood-borne pathogen which has chronically infected about 130–210 million people worldwide. Current standard-of-care (SoC) therapy is an inadequate and expensive treatment with more side effects. Two direct-acting antiviral agents (DAAs) (telaprevir and boceprevir) in combination with SoC therapy have been used in patients infected with HCV genotype 1. Although these drugs result in a shortening of therapy, they also have additional side effects and are expensive. In their stead, several second-generation DAAs are being investigated. What important is that all-oral, interferon (IFN)- and ribavirin-free regimens for the treatment of HCV-infected patients are now being investigated, and will be applied in the next year. Preventive measures against HCV, including vaccine development, are also now in progress. However, no therapeutic vaccine against HCV has been produced to date. An effective vaccine should induce robust and broadly cross-reactive CD4⁺, CD8⁺T-cell and neutralising antibody (NAb) responses. Current data indicate that vaccines can usually not completely prevent HCV infection but rather prevent the progression of HCV infection to chronic and persistent infection, which may be a realistic goal. This review discusses the important roles of NAbs and CD8⁺T-cells in the development of therapeutic vaccines, and summarizes some important epitopes of HCV recognized by CD8⁺T-cells and some prospective therapeutic vaccine approaches.