Antigenicity and immunogenicity of novel chimeric hepatitis B surface antigen particles with exposed hepatitis C virus epitopes.
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.
Netter
H J
HJ
Sir Albert Sakzewski Virus Research Centre, Royal Children's Hospital, Herston, Queensland 4029, Australia. H.Netter@mailbox.uq.edu.au
Macnaughton
T B
TB
Woo
W P
WP
Tindle
R
R
Gowans
E J
EJ
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006526:Hepatitis C / Q000517:prevention & control; D018937:Hepatitis C Antibodies / Q000097:blood*; D018936:Hepatitis C Antigens / Q000276:immunology*; D006801:Humans; D007114:Immunization; D051379:Mice; D011993:Recombinant Fusion Proteins / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology; D014761:Viral Hepatitis Vaccines / Q000276:immunology*; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*; D014771:Virion / Q000235:genetics / Q000276:immunology
D018985:Epitopes, B-Lymphocyte; C400562:HVR1 protein, Hepatitis C virus; D006514:Hepatitis B Surface Antigens; D018937:Hepatitis C Antibodies; D018936:Hepatitis C Antigens; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D014761:Viral Hepatitis Vaccines; D014764:Viral Proteins