The quality of the cellular immunity has an important influence on the clinical outcome of HCV infection. Moreover, accumulating evidence underpins the key role of broadly neutralizing antibodies (bnAbs) in the control of acute and chronic HCV infection. Notably, 20-30% of exposed individuals naturally clear the infection and immunization with recombinant glycoproteins elicits neutralizing antibodies in animal models. These findings raise hopes that development of a prophylactic HCV vaccine is possible.
The HCV surface proteins E1 and E2 are the major targets for bnAbs and therefore in the focus of vaccine research. However, HCV has evolved a number of evasion mechanisms, which complicate development of E1-E2-directed vaccines: Extensive sugar modifications of E1 and E2, and flexibility of key antibody target sites reduce immunogenicity. Moreover, most antibodies are directed against highly variable viral “decoy” target sites, which readily mutate, rendering these antibodies ineffective.