The present invention features nucleic acid constructs that can be used as a HCV nucleic acid vaccine, vaccine component, or in the production of a HCV vaccine. Described constructs include those: (1) encoding for a chimeric HCV polypeptide containing a NS3-4A region based on a first HCV strain and an NS3-NS4A-NS4B-NS5A or an NS3-NS4A-NS4B-NS5A-NS5B region based on a second strain and (2) a chimpanzee based adenovector encoding an HCV polypeptide.