title: Effects of vaccine-acquired polyclonal anti-HBs antibodies on the prevention of HBV infection of non-vaccine genotypes.
abstract: In universal hepatitis B (HB) vaccination, single vaccine-derived polyclonal anti-HBs antibodies (anti-HBs) need to inhibit infection of HB viruses (HBV) of non-vaccine genotypes. We experimentally addressed this issue.
  
  
  
  Anti-HBs-positive sera were obtained by vaccination with genotype A- or C-derived HBs antigen (HBsAg, gtA-sera or gtC-sera). Their reactivity to genotype A- and C-derived HBsAg (gtA-Ag and gtC-Ag) was measured by ELISA. The capacity of sera to neutralize HBV was evaluated using an in vitro infection model.
  
  
  
  Of 135 anti-gtA-Ag-reactive gtA-sera, 134 (99.3%) were anti-gtC-Ag-reactive. All (100%) 120 anti-gtC-Ag-reactive gtC-sera were anti-gtA-Ag-reactive. The reactivity to gtA-Ag was strongly correlated with that to gtC-Ag (gtA-sera, ρ = 0.989; gtC-sera, ρ = 0.953; p < 0.01). In gtA-sera (n = 10), anti-HBs to gtA-Ag were less completely absorbed with gtC-Ag (96.4%) than with gtA-Ag (100%, p < 0.05). Similarly, in gtC-sera (n = 10), anti-HBs to gtC-Ag were less completely absorbed with gtA-Ag (96.0%) than with gtC-Ag (100%, p < 0.01). Thus, 3.6 and 4.0% of anti-HBs in gtA-sera and gtC-sera were vaccine genotype HBsAg-specific, respectively. In the neutralization test, gtA-sera (n = 4) and gtC-sera (n = 3) with anti-HBs titers adjusted to 100 mIU/mL equally inhibited genotype C HBV infection (92.8 vs. 95.4%, p = 0.44). However, at 30 mIU/mL, the gtA-sera less effectively inhibited infection than the gtC-sera (60.2 vs. 90.2%, p < 0.05).
  
  
  
  Vaccination with genotype A- or C-derived HBsAg provided polyclonal anti-HBs that sufficiently bound to non-vaccine genotype HBsAg. However, a small portion of anti-HBs were specific to the vaccine genotype HBsAg. High anti-HBs titers would be required to prevent HBV infection of non-vaccine genotypes. UMIN/CTR UMIN000014363.
authors.affiliation: Disease Biomarker Analysis and Molecular Regulation, St. Marianna University Graduate School of Medicine, 2-16-1, Sugao, Miyamae-Ku, Kawasaki, 216-8511, Japan.|Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Kato
authors.affiliation: Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Hamada-Tsutsumi
authors.affiliation: Division of Gastroenterology and Hepatology, Kawasaki Municipal Tama Hospital, Kawasaki, Japan.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Okuse
authors.affiliation: Department of Child Health, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Sakai
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Matsumoto
authors.affiliation: Clinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine, Kawasaki, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Sato
authors.affiliation: Clinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine, Kawasaki, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sato
authors.affiliation: Clinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine, Kawasaki, Japan.
authors.forename: Mitsumi
authors.initials: M
authors.lastname: Arito
authors.affiliation: Clinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine, Kawasaki, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Omoteyama
authors.affiliation: Clinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine, Kawasaki, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Suematsu
authors.affiliation: Clinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine, Kawasaki, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Okamoto
authors.affiliation: Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Takanobu
authors.initials: T
authors.lastname: Kato
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Itoh
authors.affiliation: Department of Child Health, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Sumazaki
authors.affiliation: Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Infectious Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yotsuyanagi
authors.affiliation: Clinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine, Kawasaki, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kato
authors.affiliation: Disease Biomarker Analysis and Molecular Regulation, St. Marianna University Graduate School of Medicine, 2-16-1, Sugao, Miyamae-Ku, Kawasaki, 216-8511, Japan. manae@marianna-u.ac.jp.
authors.forename: Manae Suzuki
authors.initials: MS
authors.lastname: Kurokawa
mesh_terms: D000293:Adolescent; D000328:Adult; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D006509:Hepatitis B / Q000276:immunology / Q000517:prevention & control*; D006510:Hepatitis B Antibodies / Q000097:blood*; D006514:Hepatitis B Surface Antigens / Q000097:blood; D017325:Hepatitis B Vaccines / Q000008:administration & dosage* / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008297:Male; D014611:Vaccination; D055815:Young Adult
chemical_list: D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines
keywords: Genotypes; Hepatitis B virus; Polyclonal anti-HBs antibodies; Universal vaccination