Toth, Eric A.Chagas, AndrezzaPierce, Brian G.Fuerst, Thomas R.An effective vaccine for the hepatitis C virus (HCV) is a major unmet medical and public health need, and it requires an antigen that elicits immune responses to multiple key conserved epitopes. Decades of research have generated a number of vaccine candidates; based on these data and research through clinical development, a vaccine antigen based on the E1E2 glycoprotein complex appears to be the best choice. One bottleneck in the development of an E1E2-based vaccine is that the antigen is challenging to produce in large quantities and at high levels of purity and antigenic/functional integrity. This review describes the production and characterization of E1E2-based vaccine antigens, both membrane-associated and a novel secreted form of E1E2, with a particular emphasis on the major challenges facing the field and how those challenges can be addressed.en-UShepatitis C virus (HCV)envelope glycoproteinsE1E2E1E2 glycoprotein complexsecreted E1E2protein expressionprotein purificationbiophysical characterizationvaccine designArticle