An important consideration in the manufacture of HCV-based VLPs is the cell-type used for their manufacture. For example, it has been shown that vaccination with recombinant HCV envelope proteins expressed in mammalian cells, but not in yeast or insect cells, protect chimpanzees from primary infection by an homologous HCV isolate [20] . Similarly, Rosa et al have demonstrated that mammalian cell-derived recombinant envelope proteins bind to human cells with higher affinity than those produced in yeast or insect cells and appear to be antigenically and functionally similar to the viral proteins produced in an infected host cell [21] . More recently, vaccination of macaques using VLPs in a prime-boost regime has been reported to induce broadly neutralising antibody responses against different HCV genotypes [22] . Although all of these studies provide encouraging results supporting the development of HCV VLP-based vaccines, the fact that heterologous viral vectors and/or unrealistic dosing regimes are required to induce protective immunity indicates that it is necessary to improve their immunogenicity.