title: Molecular analysis of antigenicity and immunogenicity of a vaccine-induced escape mutant of hepatitis B virus.
abstract: BACKGROUND
  To analyze the mechanisms of mutant escape, we established a murine model of hepatitis B virus (HBV) infection and studied the interaction of the envelope protein of the virion with various kinds of anti-hepatitis B antibody.
  
  
  METHODS
  Mutation from glycine to arginine at aa145 was introduced into replication-competent DNA of HBV. The resulting mutant HBV DNA was transfected into cultured hepatoma cells and livers of mice using liposome-mediated gene transfer. Then, interactions between the antigenic envelope protein (in culture or in circulation) and anti-hepatitis B antibody were examined.
  
  
  RESULTS
  Mutant envelope protein escaped human hepatitis B immunoglobulin, rabbit polyclonal anti-hepatitis B surface antigen (HBsAg) antibody, and monoclonal anti-a antibody in vitro and in vivo. There was a difference in the degree of inhibition between hepatitis B immunoglobulin and the other two antibody types in vitro. Transfection with an HBV construct containing a mutation in the a-loop resulted in levels of HBsAg in circulation and seroconversion to anti-HBs antibody that were similar to those produced by a wild-type construct.
  
  
  CONCLUSIONS
  The degree of escape by the mutant envelope protein differed according to antibody type. Of the three types of antibody used in this study, HBV immunoglobulin was least affected by mutation in the a-loop. There appears to be no correlation between antigenicity and immunogenicity of the escape mutant, and the a-loop mutant may cause hepatitis with the usual serum viral markers.
authors.affiliation: Institute of Gastroenterology, Tokyo Women's Medical University, 8-1 Kawadacho, Shinjuku-ku, Tokyo 162-8666, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Shizuma
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Kayo
authors.initials: K
authors.lastname: Ishikawa
authors.forename: Takuma
authors.initials: T
authors.lastname: Naritomi
authors.forename: Aiko
authors.initials: A
authors.lastname: Iizuka
authors.forename: Naoko
authors.initials: N
authors.lastname: Kanai
authors.forename: Miho
authors.initials: M
authors.lastname: Ogawa
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Torii
authors.forename: Riho
authors.initials: R
authors.lastname: Joh
authors.forename: Naoaki
authors.initials: N
authors.lastname: Hayashi
mesh_terms: D000818:Animals; D015153:Blotting, Western; D006514:Hepatitis B Surface Antigens / Q000235:genetics* / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology; D007136:Immunoglobulins / Q000276:immunology; D008099:Liver / Q000166:cytology; D051379:Mice; D023421:Models, Animal; D008969:Molecular Sequence Data; D009154:Mutation; D014162:Transfection
chemical_list: D006514:Hepatitis B Surface Antigens; D007136:Immunoglobulins; C045213:hepatitis B hyperimmune globulin