Incorporation of apolipoprotein E into HBV-HCV subviral envelope particles to improve the hepatitis vaccine strategy

Sci Rep. 2021 Nov 8;11(1):21856. doi: 10.1038/s41598-021-01428-7.


Hepatitis C is a major threat to public health for which an effective treatment is available, but a prophylactic vaccine is still needed to control this disease. We designed a vaccine based on chimeric HBV-HCV envelope proteins forming subviral particles (SVPs) that induce neutralizing antibodies against HCV in vitro. Here, we aimed to increase the neutralizing potential of those antibodies, by using HBV-HCV SVPs bearing apolipoprotein E (apoE). These particles were produced by cultured stable mammalian cell clones, purified and characterized. We found that apoE was able to interact with both chimeric HBV-HCV (E1-S and E2-S) proteins, and with the wild-type HBV S protein. ApoE was also detected on the surface of purified SVPs and improved the folding of HCV envelope proteins, but its presence lowered the incorporation of E2-S protein. Immunization of New Zealand rabbits resulted in similar anti-S responses for all rabbits, whereas anti-E1/-E2 antibody titers varied according to the presence or absence of apoE. Regarding the neutralizing potential of these anti-E1/-E2 antibodies, it was higher in rabbits immunized with apoE-bearing particles. In conclusion, the association of apoE with HCV envelope proteins may be a good strategy for improving HCV vaccines based on viral envelope proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / biosynthesis
  • Antibodies, Neutralizing / blood
  • Antigen Presentation / immunology
  • Apolipoproteins E / administration & dosage*
  • Apolipoproteins E / immunology*
  • Cell Line
  • Female
  • Hepacivirus / immunology*
  • Hepatitis B virus / immunology*
  • Hepatitis C / immunology
  • Hepatitis C / prevention & control
  • Hepatitis C Antibodies / biosynthesis
  • Hepatitis C Antibodies / blood
  • Humans
  • Immune Evasion
  • Rabbits
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / immunology
  • Viral Envelope Proteins / administration & dosage
  • Viral Envelope Proteins / immunology
  • Viral Hepatitis Vaccines / administration & dosage*
  • Viral Hepatitis Vaccines / immunology*


  • Antibodies, Neutralizing
  • Apolipoproteins E
  • Hepatitis C Antibodies
  • Recombinant Fusion Proteins
  • Viral Envelope Proteins
  • Viral Hepatitis Vaccines