Induction of broadly neutralizing antibodies using a secreted form of the hepatitis C virus E1E2 heterodimer as a vaccine candidate

Proc Natl Acad Sci U S A. 2022 Mar 15;119(11):e2112008119. doi: 10.1073/pnas.2112008119. Epub 2022 Mar 9.


SignificanceHepatitis C virus chronically infects approximately 1% of the world's population, making an effective vaccine for hepatitis C virus a major unmet public health need. The membrane-associated E1E2 envelope glycoprotein has been used in clinical studies as a vaccine candidate. However, limited neutralization breadth and difficulty in producing large amounts of homogeneous membrane-associated E1E2 have hampered efforts to develop an E1E2-based vaccine. Our previous work described the design and biochemical validation of a native-like soluble secreted form of E1E2 (sE1E2). Here, we describe the immunogenic characterization of the sE1E2 complex. sE1E2 elicited broadly neutralizing antibodies in immunized mice, with increased neutralization breadth relative to the membrane-associated E1E2, thereby validating this platform as a promising model system for vaccine development.

Keywords: E1E2 envelope glycoproteins; hepatitis C virus; secreted; vaccine.

MeSH terms

  • Animals
  • Broadly Neutralizing Antibodies* / biosynthesis
  • Broadly Neutralizing Antibodies* / blood
  • Hepatitis C Antibodies* / biosynthesis
  • Hepatitis C Antibodies* / blood
  • Hepatitis C* / prevention & control
  • Immunogenicity, Vaccine*
  • Mice
  • Protein Multimerization
  • Viral Envelope Proteins* / chemistry
  • Viral Envelope Proteins* / immunology
  • Viral Hepatitis Vaccines* / chemistry
  • Viral Hepatitis Vaccines* / immunology


  • Broadly Neutralizing Antibodies
  • E1 protein, Hepatitis C virus
  • Hepatitis C Antibodies
  • Viral Envelope Proteins
  • Viral Hepatitis Vaccines
  • glycoprotein E2, Hepatitis C virus