title: Chimeric hepatitis B virus/hepatitis C virus envelope proteins elicit broadly neutralizing antibodies and constitute a potential bivalent prophylactic vaccine.
abstract: The development of a prophylactic vaccine against hepatitis C virus (HCV) has become an important medical priority, because 3-4 million new HCV infections are thought to occur each year worldwide. Hepatitis B virus (HBV) is another major human pathogen, but infections with this virus can be prevented with a safe, efficient vaccine, based on the remarkable ability of the envelope protein (S) of this virus to self-assemble into highly immunogenic subviral particles. Chimeric HBV-HCV envelope proteins in which the N-terminal transmembrane domain of S was replaced with the transmembrane domain of the HCV envelope proteins (E1 or E2) were efficiently coassembled with the wild-type HBV S protein into subviral particles. These chimeric particles presented the full-length E1 and E2 proteins from a genotype 1a virus in an appropriate conformation for formation of the E1-E2 heterodimer. Produced in stably transduced Chinese hamster ovary cells and used to immunize New Zealand rabbits, these particles induced a strong specific antibody (Ab) response against the HCV and HBV envelope proteins in immunized animals. Sera containing anti-E1 or anti-E2 Abs elicited by these particles neutralized infections with HCV pseudoparticles and cell-cultured viruses derived from different heterologous 1a, 1b, 2a, and 3 strains. Moreover, the anti-hepatitis B surface response induced by these chimeric particles was equivalent to the response induced by a commercial HBV vaccine.
  
  
  CONCLUSIONS
  Our results provide support for approaches based on the development of bivalent HBV-HCV prophylactic vaccine candidates potentially able to prevent initial infection with either of these two hepatotropic viruses.
authors.affiliation: INSERM U966, Université François Rabelais and CHRU de Tours, Tours, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Beaumont
authors.forename: Romuald
authors.initials: R
authors.lastname: Patient
authors.forename: Christophe
authors.initials: C
authors.lastname: Hourioux
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dimier-Poisson
authors.forename: Philippe
authors.initials: P
authors.lastname: Roingeard
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology* / Q000378:metabolism; D000914:Antibodies, Viral / Q000276:immunology* / Q000378:metabolism; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004195:Disease Models, Animal; D005260:Female; D016174:Hepacivirus / Q000276:immunology* / Q000378:metabolism; D006509:Hepatitis B / Q000517:prevention & control; D006515:Hepatitis B virus / Q000276:immunology* / Q000378:metabolism; D006526:Hepatitis C / Q000517:prevention & control; D056724:Immunity, Humoral / Q000276:immunology; D017510:Protein Folding; D011817:Rabbits; D014759:Viral Envelope Proteins / Q000276:immunology* / Q000378:metabolism; D014761:Viral Hepatitis Vaccines / Q000276:immunology* / Q000627:therapeutic use
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D014759:Viral Envelope Proteins; D014761:Viral Hepatitis Vaccines