在动物模型中妊娠期间乙型肝炎中和抗体的经胎盘转移:对新生儿和产妇健康的影响

Hepatitis research and treatment Pub Date : 2014-01-01 Epub Date: 2014-03-27 DOI:10.1155/2014/159206
Li Ma, Malgorzata G Norton, Iftekhar Mahmood, Zhong Zhao, Lilin Zhong, Pei Zhang, Evi B Struble
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摘要

尽管新生儿暴露后预防 (PEP) 在预防乙型肝炎病毒母婴传播方面取得了成功,但在非美国的临床试验中,在妊娠末期为母亲注射乙型肝炎免疫球蛋白 (HBIG)(以及新生儿被动式暴露后预防)只能部分改善结果。也就是说,相当大比例的新生儿在出生后第一年就受到了感染。我们利用人类 IgG 经胎盘转移的相关动物模型来研究妊娠末期 HBV 中和抗体(nAb)母体和胎儿水平的剂量、时间和亚类依赖性。怀孕豚鼠在分娩前 2-5 天接受 50 或 100 IU/kg HBIGIV。对母体及其胎儿的人类总 IgG、IgG 亚类和 nAb 进行了测定。此外,还对豚鼠 Fc 新生儿受体与 HBIGIV 以及所有人类 IgG 亚类的结合进行了体外分析。我们的研究表明,妊娠豚鼠体内的 nAb 经胎盘转移到了仔鼠体内;在分娩过程中没有发生转移。转移的 nAb 量与剂量和时间有关。因此,在临床上选择有效的剂量非常重要:微量剂量可能是剂量不足,尤其是在病毒血症较高的情况下。
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Transplacental Transfer of Hepatitis B Neutralizing Antibody during Pregnancy in an Animal Model: Implications for Newborn and Maternal Health.

Despite the success of postexposure prophylaxis (PEP) of the newborn in preventing mother-to-child transmission of hepatitis B virus), in non-US clinical trials, administering hepatitis B immune globulin (HBIG) to mothers at the end of pregnancy (in addition to passive-active PEP of the newborn) only partially improved outcomes. That is, a significant percentage of newborns became infected during their first year of life. We used a relevant animal model for human IgG transplacental transfer to study dose, time and subclass dependence of HBV neutralizing antibody (nAb) maternal, and fetal levels at the end of pregnancy. Pregnant guinea pigs received 50 or 100 IU/kg HBIGIV 2-5 days before delivery. Human total IgG, IgG subclasses, and nAb in mothers and their litters were measured. In vitro analyses of guinea pig Fc neonatal receptor binding to HBIGIV, as well as to all human IgG subclasses, were also performed. Our study showed that nAb transferred transplacentally from the pregnant guinea pigs to their litters; no transfer occurred during parturition. The amount of the transferred nAb was dose and time dependent. Thus, selection of an efficacious dose in the clinic is important: microdosing may be underdosing, particularly in cases of high viraemia.

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