1Disease Biomarker Analysis and Molecular Regulation, St. Marianna University Graduate School of Medicine, 2-16-1, Sugao, Miyamae-Ku, Kawasaki, 216-8511, Japan.
2Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan.
3Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
4Division of Gastroenterology and Hepatology, Kawasaki Municipal Tama Hospital, Kawasaki, Japan.
5Department of Child Health, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
6Clinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine, Kawasaki, Japan.
7Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.
8Department of Infectious Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
9Disease Biomarker Analysis and Molecular Regulation, St. Marianna University Graduate School of Medicine, 2-16-1, Sugao, Miyamae-Ku, Kawasaki, 216-8511, Japan. [email protected].
AbstractBACKGROUND: 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.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: 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.
KEYWORDS: Genotypes; Hepatitis B virus; Polyclonal anti-HBs antibodies; Universal vaccination
1Disease Biomarker Analysis and Molecular Regulation,St.Marianna University Graduate School of Medicine,2-16-1,Sugao,Miyamae-Ku,Kawasaki,216-8511,Japan。
日本川崎市的圣玛丽安娜大学医学院内科学的胃肠病学和肝脏病学的2Division。
名古屋市立大学大学院医学科学研究科病毒学与肝脏病学室,名古屋市。
4Division of Gastroenterology and Hepatology,Kawasaki Municipal Tama Hospital,Kawasaki,Japan。
5日本筑波大学医学部儿童健康科。
6临床蛋白质组学和分子医学,圣玛丽安娜大学医学研究生院,川崎,日本。
7日本东京国立传染病研究所病毒学II部。
8日本东京大学医学研究科传染病教授。
9Disease Biomarker Analysis and Molecular Regulation,St.Marianna University Graduate School of Medicine,2-16-1,Sugao,Miyamae-Ku,Kawasaki,216-8511,Japan。 [email protected]。