Approximately 71 million people are infected with hepatitis C virus causing substantial morbidity and mortality worldwide. Efforts to eliminate HCV have been improved with the development of safe and highly effective direct-acting antivirals, but for elimination to be achieved, a vaccine must be developed to reduce the number of new infections and prevent reinfection. To date, no pathogen has been eliminated without the development of a prophylactic vaccine. Chimpanzee adenovirus (ChAd) is a leading vaccine platform for COVID-19 aimed at generating neutralizing antibodies to the SARS-CoV-2 spike protein. It is a viral vector platform developed at Oxford University from a genetically modified attenuated rare serotype (ChAdOx1), therefore there is low seroprevalence in the human population which will circumvent pre-existing immunity. We investigated the use of this platform with a leading HCV vaccine candidate aimed at generating humoral immunity. We have previously reported that by removing the hypervariable regions from glycoprotein E2 a soluble recombinant protein (D123) can be produced and was shown to elicit cross neutralising antibodies in guinea pigs when administered as an adjuvanted soluble protein. In this study, we delivered the D123 vaccine candidate in ChAdOx1 and investigated the optimal prime-boost strategy. Animals were administered three doses, three weeks apart of either ChAdOx1D123, ChAdOx1D123 and boosted with soluble adjuvanted D123, or three doses of soluble adjuvanted D123 protein. All strategies elicited E2 specific antibodies in mice, however, titres were significantly higher in groups that received D123 protein, either as a boost with ChAdOx1D123 prime or three doses of D123. Enhanced antibody mediated E2-CD81 inhibition was observed to be statistically highest using ChAdOx1D123 prime/D123 protein boost, with this heterologous combination also eliciting both type specific and cross neutralising antibodies. Type specific neutralising antibodies were targeted to 3 major neutralisation epitopes located at residues 412-428, 429-448 and 523-549 which includes the CD81 binding loop. The results of this study show that addition of a protein boost after a ChAdOx1 prime using D123 is the optimal strategy for delivering a B cell immunogen for an HCV vaccine and suggests that this strategy could be explored for other pathogens including COVID-19.