title: A novel hepatitis B virus surface antigen immunoassay as sensitive as hepatitis B virus nucleic acid testing in detecting early infection.
abstract: BACKGROUND
  The aim was to considerably enhance the sensitivity of hepatitis B virus (HBV) surface antigen (HBsAg) detection and investigate whether the window period for HBV detection could be reduced.
  
  
  METHODS
  A high-sensitivity chemiluminescent enzyme immunoassay (CLEIA) was developed for quantitative HBsAg detection by a combination of monoclonal antibodies, each one for a specific epitope of HBsAg, and by improving the conjugation technique. The sensitivity of the assay was compared with that of the existing chemiluminescent immunoassay (CLIA). Commercially available seroconversion panels and samples of HBV-infected chimpanzees were tested with the developed prototype to assess whether the window period for HBsAg detection could be reduced to that for DNA detection.
  
  
  RESULTS
  Compared to the existing CLIA, the CLEIA prototype detected HBsAg with approximately 230-fold higher sensitivity and showed a reduced window period. HBsAg detection by the CLEIA prototype and HBV DNA detection by polymerase chain reaction (PCR) occurred simultaneously. The mean time for the CLEIA prototype to first detect HBsAg was approximately 17.4 days less than that for the existing systems. Further, CLEIA prototype enabled HBsAg detection even in anti-HBs-positive seroconversion samples. In the inoculated chimpanzees the HBsAg and HBV DNA became detectable simultaneously and concentrations increased in parallel, whereas HBsAg remained detectable longer than HBV DNA in the declining phase of viremia.
  
  
  CONCLUSIONS
  The CLEIA prototype yielded results comparable with those of HBV DNA PCR. This novel high-sensitivity assay may be useful for early detection of HBV infection and monitoring patients with a history of infection.
authors.affiliation: R&D Division, Advanced Life Science Institute, Inc., Saitama, Japan. nnagata@alsi-i.co.jp
authors.forename: Naoko
authors.initials: N
authors.lastname: Matsubara
authors.forename: Osamu
authors.initials: O
authors.lastname: Kusano
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Sugamata
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Itoh
authors.forename: Masaaki
authors.initials: M
authors.lastname: Mizuii
authors.forename: Junko
authors.initials: J
authors.lastname: Tanaka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yoshizawa
mesh_terms: D000818:Animals; D004279:DNA, Viral / Q000235:genetics* / Q000378:metabolism; D006509:Hepatitis B / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D006514:Hepatitis B Surface Antigens / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D007118:Immunoassay / Q000379:methods*; D007201:Indicator Dilution Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D002679:Pan troglodytes; D013379:Substrate Specificity; D013997:Time Factors
chemical_list: D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens