title: Induction of oral tolerance towards hepatitis B envelope antigens in a murine model.
abstract: BACKGROUND
  Hepatitis B virus (HBV) is a non-cytopathic virus, and the hepatocellular injury that occurs as a consequence of HBV infection is mediated by the host antiviral immune response. Subjects with natural tolerance to HBV have minimal or no liver injury despite chronic viremia. We have shown that immune tolerance towards viruses can be induced by oral administration of viral proteins.
  
  
  OBJECTIVE
  To test whether oral induction of tolerance can be induced towards HBV antigens, and whether oral tolerance induction downregulates preexisting anti-HBV immune response.
  
  
  METHODS
  Oral tolerance was induced via feeding of five low oral doses of HBV proteins (HBsAg+preS1+preS2, BioHepB). This was followed by two inoculations with the BioHepB vaccine. Humoral immune tolerance was evaluated by measuring serum levels of anti-HBs antibody titers at monthly intervals. To determine if oral tolerance induction downregulates pre-existing anti-HBs immunity, mice were inoculated twice with the BioHepB vaccine, followed by feeding of BioHepB-HBV proteins.
  
  
  RESULTS
  Feeding of HBV proteins markedly inhibited production of anti-HBs antibodies in naive mice. Anti-HBs titers were 45 versus 135 mIU/ml, in tolerized versus non-tolerized controls (P<0.005). Moreover, oral tolerance induction effectively down-regulated pre-existing immunity and reduced the anti-HBs titers in previously immunized mice to 112 versus 223 mIU/ml, in tolerized compared with non-tolerized controls (P<0.01).
  
  
  CONCLUSIONS
  Induction of oral tolerance towards HBV proteins downregulates the antiviral humoral immune response in naive mice, and in the presence of preexisting anti-HBV immunity. This approach should be further investigated as a method for alleviation of antiviral-mediated liver injury in chronic HBV hepatitis.
authors.affiliation: Department of Medicine, Liver Unit, Hadassah University Hospital, PO Box 12000, IL91120, Jerusalem, Israel.
authors.forename: I
authors.initials: I
authors.lastname: Gotsman
authors.forename: R
authors.initials: R
authors.lastname: Beinart
authors.forename: R
authors.initials: R
authors.lastname: Alper
authors.forename: E
authors.initials: E
authors.lastname: Rabbani
authors.forename: D
authors.initials: D
authors.lastname: Engelhardt
authors.forename: Y
authors.initials: Y
authors.lastname: Ilan
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D006510:Hepatitis B Antibodies / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000008:administration & dosage* / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000276:immunology; D006515:Hepatitis B virus / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000276:immunology* / Q000628:therapy*; D006801:Humans; D007108:Immune Tolerance; D051379:Mice; D008807:Mice, Inbred BALB C; D014611:Vaccination
chemical_list: D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines