疫苗获得性多克隆抗HBs抗体对预防非疫苗基因型的HBV感染的

StephenW

J Gastroenterol. 2017 Feb 14. doi: 10.1007/s00535-017-1316-3. [Epub ahead of print]
Effects of vaccine-acquired polyclonal anti-HBs antibodies on the prevention of HBV infection of non-vaccine genotypes.Kato M1,2, Hamada-Tsutsumi S3, Okuse C4, Sakai A5, Matsumoto N2, Sato M6, Sato T6, Arito M6, Omoteyama K6, Suematsu N6, Okamoto K6, Kato T7, Itoh F2, Sumazaki R5, Tanaka Y3, Yotsuyanagi H8, Kato T6, Kurokawa MS9.
Author information

• 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

PMID:28197802DOI:10.1007/s00535-017-1316-3

StephenW

J Gastroenterol。 2017年2月14日。doi：10.1007 / s00535-017-1316-3。 [印刷前电子版]
疫苗获得性多克隆抗HBs抗体对预防非疫苗基因型的HBV感染的效果。
Kato M1,2，Hamada-Tsutsumi S3，Okuse C4，Sakai A5，Matsumoto N2，Sato M6，Sato T6，Arito M6，Omoteyama K6，Suematsu N6，Okamoto K6，Kato T7，Itoh F2，Sumazaki R5，Tanaka Y3，Yotsuyanagi H8，Kato T6，Kurokawa MS9。
作者信息

    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]。

抽象
背景：

在普遍性乙型肝炎（HB）疫苗接种中，单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）的感染。我们实验地解决了这个问题。
方法：

通过用基因型A或C衍生的HBs抗原（HBsAg，gtA-血清或gtC-血清）接种获得抗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价血清中和HBV的能力。
结果：

在135种抗-gtA-Ag-反应性gtA血清中，134种（99.3％）是抗-κC-Ag-反应性的。所有（100％）120抗-κC-Ag-反应性gtC-血清是抗-κA-Ag-反应性的。对gtA-Ag的反应性与对gtC-Ag的反应性（gtA-血清，ρ= 0.989; gtC-血清，ρ= 0.953; p <0.01）强相关。在gtA血清（n = 10）中，gt-Ag（96.4％）比gtA-Ag（100％，p <0.05）更少地完全吸收抗HBs至gtA-Ag。类似地，在gtC-血清（n = 10）中，gtC-Ag的抗HBs与gtA-Ag（96.0％）比用gtC-Ag（100％，p <0.01）较少完全吸收。因此，在gtA血清和gtC-血清中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，抗HBs滴度调节至100mIU / mL的gtA血清（n = 4）和gtC-血清（n = 3）同样抑制基因型C HBV感染（92.8对比95.4％，p = 0.44） 。然而，在30mIU / mL，gtA血清比gtC-血清不太有效地抑制感染（60.2对比90.2％，p <0.05）。
结论：

用基因型A或C衍生的HBsAg疫苗接种提供了与非疫苗基因型HBsAg充分结合的多克隆抗HBs。然而，一小部分抗HBs对疫苗基因型HBsAg是特异性的。需要高抗HBs滴度以防止非疫苗基因型的HBV感染。 UMIN / CTR UMIN000014363。
关键词：

基因型;乙型肝炎病毒;多克隆抗HBs抗体;普遍接种

PMID：
    28197802
DOI：
    10.1007 / s00535-017- 1316-3