Antigenicity and immunogenicity of novel chimeric hepatitis B surface antigen particles with exposed hepatitis C virus epitopes

J Virol. 2001 Mar;75(5):2130-41. doi: 10.1128/JVI.75.5.2130-2141.2001.

Abstract

The small envelope protein of hepatitis B virus (HBsAg-S) can self-assemble into highly organized virus like particles (VLPs) and induce an effective immune response. In this study, a restriction enzyme site was engineered into the cDNA of HBsAg-S at a position corresponding to the exposed site within the hydrophilic a determinant region (amino acid [aa] 127-128) to create a novel HBsAg vaccine vector allowing surface orientation of the inserted sequence. We inserted sequences of various lengths from hypervariable region 1 (HVR1) of the hepatitis C virus (HCV) E2 protein containing immunodominant epitopes and demonstrated secretion of the recombinant HBsAg VLPs from transfected mammalian cells. A number of different recombinant proteins were synthesized, and HBsAg VLPs containing inserts up to 36 aa were secreted with an efficiency similar to that of wild-type HBsAg. The HVR1 region exposed on the particles retained an antigenic structure similar to that recognized immunologically during natural infection. VLPs containing epitopes from either HCV-1a or -1b strains were produced that induced strain-specific antibody responses in immunized mice. Injection of a combination of these VLPs induced antibodies against both HVR1 epitopes that resulted in higher titers than were achieved by vaccination with the individual VLPs, suggesting a synergistic effect. This may lead to the development of recombinant particles which are able to induce a broad anti-HCV immune response against the HCV quasispecies or other quasispecies-like infectious agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology
  • Epitopes, B-Lymphocyte / immunology
  • Hepacivirus / genetics
  • Hepacivirus / immunology*
  • Hepatitis B Surface Antigens / genetics
  • Hepatitis B Surface Antigens / immunology*
  • Hepatitis B Surface Antigens / metabolism
  • Hepatitis B virus / genetics
  • Hepatitis B virus / immunology
  • Hepatitis B virus / metabolism
  • Hepatitis C / prevention & control
  • Hepatitis C Antibodies / blood*
  • Hepatitis C Antigens / immunology*
  • Humans
  • Immunization
  • Mice
  • Recombinant Fusion Proteins / immunology
  • Vaccines, Synthetic / immunology
  • Viral Hepatitis Vaccines / immunology*
  • Viral Proteins / genetics
  • Viral Proteins / immunology*
  • Virion / genetics
  • Virion / immunology

Substances

  • Epitopes, B-Lymphocyte
  • HVR1 protein, Hepatitis C virus
  • Hepatitis B Surface Antigens
  • Hepatitis C Antibodies
  • Hepatitis C Antigens
  • Recombinant Fusion Proteins
  • Vaccines, Synthetic
  • Viral Hepatitis Vaccines
  • Viral Proteins