Immunizations with chimeric hepatitis B virus-like particles to induce potential anti-hepatitis C virus neutralizing antibodies.
BACKGROUND
Virus-like particles (VLPs) are highly immunogenic and proven to induce protective immunity. The small surface antigen (HBsAg-S) of hepatitis B virus (HBV) self-assembles into VLPs and its use as a vaccine results in protective antiviral immunity against HBV infections. Chimeric HBsAg-S proteins carrying foreign epitopes allow particle formation and have the ability to induce anti-foreign humoral and cellular immune responses.


RESULTS
The insertion of the hypervariable region 1 (HVR1) sequence derived from the envelope protein 2 (E2) of hepatitis C virus (HCV) into the major antigenic site of HBsAg-S ('a'-determinant) resulted in the formation of highly immunogenic VLPs that retained the antigenicity of the inserted HVR1 sequence. BALB/c mice were immunized with chimeric VLPs, which resulted in antisera with anti-HCV activity. The antisera were able to immunoprecipitate native HCV envelope complexes (E1E2) containing homologous or heterologous HVR1 sequences. HCV E1E2 pseudotyped HIV-1 particles (HCVpp) were used to measure entry into HuH-7 target cells in the presence or absence of antisera that were raised against chimeric VLPs. Anti-HVR1 VLP sera interfered with entry of entry-competent HCVpps containing either homologous or heterologous HVR1 sequences. Also, immunizations with chimeric VLPs induced antisurface antigen (HBsAg) antibodies, indicating that HBV-specific antigenicity and immunogenicity of the 'a'-determinant region is retained.


CONCLUSIONS
A multivalent vaccine against different pathogens based on the HBsAg delivery platform should be possible. We hypothesize that custom design of VLPs with an appropriate set of HCV-neutralizing epitopes will induce antibodies that would serve to decrease the viral load at the initial infecting inoculum.
Department of Microbiology, Monash University, Clayton, Victoria, Australia.
Patricia T K
PT
Vietheer
Irene
I
Boo
Heidi E
HE
Drummer
Hans-Jürgen
HJ
Netter
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D016174:Hepacivirus / 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*; D006801:Humans; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014761:Viral Hepatitis Vaccines / Q000008:administration & dosage* / Q000276:immunology; D014771:Virion / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D006514:Hepatitis B Surface Antigens; D018937:Hepatitis C Antibodies; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; D014761:Viral Hepatitis Vaccines; C091015:glycoprotein E2, Hepatitis C virus