Structural and Biophysical Characterization of the HCV E1E2 Heterodimer for Vaccine Development

Viruses. 2021 May 29;13(6):1027. doi: 10.3390/v13061027.


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.

Keywords: E1; E1E2 glycoprotein complex; E2; biophysical characterization; envelope glycoproteins; hepatitis C virus (HCV); protein expression; protein purification; secreted E1E2; vaccine design.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Epitopes / immunology
  • HEK293 Cells
  • Hepacivirus / chemistry*
  • Hepacivirus / genetics
  • Hepacivirus / immunology
  • Hepatitis C / prevention & control*
  • Hepatitis C / virology
  • Humans
  • Mice
  • Models, Molecular
  • Protein Conformation
  • Protein Multimerization
  • Viral Envelope Proteins / chemistry*
  • Viral Envelope Proteins / immunology
  • Viral Envelope Proteins / metabolism
  • Viral Hepatitis Vaccines / chemistry*


  • Epitopes
  • Viral Envelope Proteins
  • Viral Hepatitis Vaccines