title: Characterization of the 3rd International Standard for hepatitis B virus surface antigen (HBsAg).
abstract: HBsAg is the most important marker for laboratory diagnosis of HBV infection. Validation and quality control of HBsAg tests requires International Standards (IS). Recently the 2nd IS was replaced by the 3rd IS. Both IS are made from plasma-derived hepatitis B vaccines, but production and geographical origin are different.
  
  
  
  Characterization of the HBsAg in the source material (SM) for the 3rd IS and comparison with the 2nd IS and native HBsAg.
  
  
  
  The SM was analyzed using solid-phase immunoassays, quantitative immune electrophoresis, ultracentrifugation, immunoblotting and HBV DNA sequencing.
  
  
  
  The plasma-derived HBsAg of the SM originated from at least two different HBV strains, both of subgenotype (sgt) B4, typical for Vietnam. The HBsAg subtype was heterogeneous with ayw1 and adw2. The HBsAg concentration was 23,700 IU/ml as determined by solid-phase immunoassay; immune electrophoresis calibrated with sgt B2 revealed a concentration of 24,500 IU/ml while calibration with sgt D1 provided lower values. Proteins in the SM are heterogeneous in size containing only traces of preS. The protein subunits are partially cross-linked.
  
  
  
  The antigenicity of the 3rd IS is suitable for HBsAg calibration in laboratory tests. In contrast to the 2nd IS, the 3rd IS is representative for a highly endemic region. Similar to the 2nd IS and different from native HBsAg, preS domains are depleted, protein subunits are partially cross-linked and the HBsAg particles are partially aggregated in the 3rd IS. The HBV subgenotype differences between the two IS may lead to variations in different quantitative assays.
authors.affiliation: Institute of Medical Virology, Justus Liebig University Giessen, National Reference Centre for Hepatitis B and D Viruses, German Center for Infection Research, Biomedical Research Center Seltersberg, Schubertstr. 81, 35392 Giessen, Germany.
authors.forename: Pia L
authors.initials: PL
authors.lastname: Seiz
authors.affiliation: Institute of Medical Virology, Justus Liebig University Giessen, National Reference Centre for Hepatitis B and D Viruses, German Center for Infection Research, Biomedical Research Center Seltersberg, Schubertstr. 81, 35392 Giessen, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Mohr
authors.affiliation: National Institute for Biological Standards and Control (NIBSC), Blanche Lane, South Mimms, Potters Bar, Hertfordshire, EN6 3QG UK.
authors.forename: Dianna E
authors.initials: DE
authors.lastname: Wilkinson
authors.affiliation: Institute of Medical Virology, Justus Liebig University Giessen, National Reference Centre for Hepatitis B and D Viruses, German Center for Infection Research, Biomedical Research Center Seltersberg, Schubertstr. 81, 35392 Giessen, Germany.
authors.forename: John
authors.initials: J
authors.lastname: Ziebuhr
authors.affiliation: Institute of Medical Virology, Justus Liebig University Giessen, National Reference Centre for Hepatitis B and D Viruses, German Center for Infection Research, Biomedical Research Center Seltersberg, Schubertstr. 81, 35392 Giessen, Germany.
authors.forename: Christian G
authors.initials: CG
authors.lastname: Schüttler
authors.affiliation: Institute of Medical Virology, Justus Liebig University Giessen, National Reference Centre for Hepatitis B and D Viruses, German Center for Infection Research, Biomedical Research Center Seltersberg, Schubertstr. 81, 35392 Giessen, Germany.
authors.forename: Wolfram H
authors.initials: WH
authors.lastname: Gerlich
authors.affiliation: Institute of Medical Virology, Justus Liebig University Giessen, National Reference Centre for Hepatitis B and D Viruses, German Center for Infection Research, Biomedical Research Center Seltersberg, Schubertstr. 81, 35392 Giessen, Germany. Electronic address: dieter.glebe@viro.med.uni-giessen.de.
authors.forename: Dieter
authors.initials: D
authors.lastname: Glebe
mesh_terms: D006509:Hepatitis B / Q000175:diagnosis*; D006514:Hepatitis B Surface Antigens / Q000032:analysis*; D006801:Humans; D007118:Immunoassay / Q000592:standards*; D012015:Reference Standards; D012698:Serologic Tests / Q000592:standards*
chemical_list: D006514:Hepatitis B Surface Antigens
keywords: HBV diagnostics; HBV subgenotype; HBsAg; Immunoassay; International Standard