Struble Evi Budo, Ma Li, Zhong Lilin, Lesher A, Beren Joel, Zhang Pei
Laboratory of Plasma Derivatives, Division of Hematology, OBRR, FDA, Bethesda, MD 20892, USA.
Clin Dev Immunol. 2012;2012:538701. doi: 10.1155/2012/538701. Epub 2012 Sep 9.
Despite increased use of monoclonal and polyclonal antibody therapies, including during pregnancy, there is little data on appropriate animal models that could humanely be used to understand determinants of protection and to evaluate safety of these biologics in the mother and the developing fetus. Here, we demonstrate that pregnant guinea pigs can transport human IgG transplacentally at the end of pregnancy. We also observe that human IgG binds to an engineered soluble variant of the guinea pig neonatal Fc receptor in vitro in a manner similar to that demonstrated for the human variant, suggesting that this transplacental transport mirrors the receptor-based mechanism seen in humans. Using an intravenous antihepatitis B-specific immune globulin preparation as an example, we show that this transport results in neutralizing activity in the mother and the newborn that would potentially be prophylactic against hepatitis B viral infection. These preliminary data lay the groundwork for introducing pregnant guinea pigs as an appropriate model for the evaluation of antibody therapies and advancing the health of women and neonates.
尽管单克隆和多克隆抗体疗法的使用有所增加，包括在孕期的使用，但关于可人道地用于了解保护决定因素以及评估这些生物制剂在母亲和发育中的胎儿体内安全性的合适动物模型的数据却很少。在此，我们证明怀孕的豚鼠在妊娠末期可经胎盘转运人IgG。我们还观察到，人IgG在体外与豚鼠新生儿Fc受体的工程化可溶性变体结合，其方式与在人类变体中所显示的方式相似，这表明这种经胎盘转运反映了在人类中所见的基于受体的机制。以静脉注射抗乙型肝炎特异性免疫球蛋白制剂为例，我们表明这种转运在母亲和新生儿体内产生了中和活性，这可能对预防乙型肝炎病毒感染具有保护作用。这些初步数据为引入怀孕豚鼠作为评估抗体疗法的合适模型以及促进妇女和新生儿健康奠定了基础。
