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.
J Gastroenterol. 2017 Sep;52(9):1051-1063. doi: 10.1007/s00535-017-1316-3. Epub 2017 Feb 14.
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.
在普遍的乙型肝炎（HB）疫苗接种中，单一疫苗衍生的多克隆抗-HBs 抗体（抗-HBs）需要抑制非疫苗基因型的 HB 病毒（HBV）感染。我们通过实验解决了这个问题。
通过接种基因型 A 或 C 来源的 HBs 抗原（HBsAg，gtA 血清或 gtC 血清）获得抗-HBs 阳性血清。通过 ELISA 测量它们对基因型 A 和 C 衍生的 HBsAg（gtA-Ag 和 gtC-Ag）的反应性。使用体外感染模型评估血清中和 HBV 的能力。
在 135 种抗-gtA-Ag 反应性的 gtA 血清中，134 种（99.3%）对 gtC-Ag 反应性。所有（100%）120 种抗-gtC-Ag 反应性的 gtC 血清都对 gtA-Ag 反应性。对 gtA-Ag 的反应性与对 gtC-Ag 的反应性呈强相关性（gtA 血清，ρ=0.989；gtC 血清，ρ=0.953；p<0.01）。在 gtA 血清（n=10）中，抗-HBs 与 gtC-Ag 的结合不如与 gtA-Ag 完全（96.4% vs. 100%，p<0.05）。同样，在 gtC 血清（n=10）中，抗-HBs 与 gtA-Ag 的结合不如与 gtC-Ag 完全（96.0% vs. 100%，p<0.01）。因此，gtA 血清和 gtC 血清中的 3.6%和 4.0%的抗-HBs 分别是疫苗基因型 HBsAg 特异性的。在中和试验中，将抗-HBs 滴度调整至 100 mIU/mL 的 gtA 血清（n=4）和 gtC 血清（n=3）同样抑制了基因型 C HBV 感染（92.8% vs. 95.4%，p=0.44）。然而，在 30 mIU/mL 时，gtA 血清的抑制感染效果不如 gtC 血清（60.2% vs. 90.2%，p<0.05）。
接种基因型 A 或 C 来源的 HBsAg 提供了能够与非疫苗基因型 HBsAg 充分结合的多克隆抗-HBs。然而，一小部分抗-HBs 是针对疫苗基因型 HBsAg 的特异性的。需要高滴度的抗-HBs 来预防非疫苗基因型的 HBV 感染。UMIN/CTR UMIN000014363。
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