Department of Veterinary Biosciences, Ohio State University, Columbus, Ohio;, Email:
Department of Veterinary Biosciences, Ohio State University, Columbus, Ohio.
Comp Med. 2020 Dec 1;70(6):510-519. doi: 10.30802/AALAS-CM-20-000040. Epub 2020 Oct 29.
Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and viral pneumonia in infants and young children worldwide. Currently no vaccine is available to prevent RSV infection, but virus-neutralizing monoclonal antibodies can be given prophylactically, emphasizing the protective potential of antibodies. One concept of RSV vaccinology is mothers' immunization to induce high antibody titers, leading to passive transfer of high levels of maternal antibody to the fetus through the placenta and to the neonate through colostrum. Cotton rats are an excellent small animal model for RSV infection and have been used to test maternal immunization. To mechanistically understand antibody transfer in the cotton rat model, we characterized the cotton rat placenta and Fc receptor localization. Placentas from cotton rats at midgestation (approximately day 14) and at late gestation (approximately day 25) and neonatal (younger than 1 wk) gastrointestinal tracts were collected for light microscopy, immunohistochemistry, and transmission electron microscopy. The cotton rat placenta is hemotrichorial and has 5 distinct layers: decidua, junctional zone, labyrinth, chorionic plate, and yolk sac. Consistent with the transfer of maternal antibodies, the majority of the Fc receptors are present in the yolk sac endoderm and fetal capillary endothelium of the chorionic plate, involving 10% of the cells within the labyrinth. In addition, Fc receptors are present on duodenal and jejunal enterocytes in cotton rats, similar to humans, mice, and rats. These findings provide the structural basis for the pre- and postnatal transfer of maternal antibodies described in cotton rats.
呼吸道合胞病毒(RSV)是全球婴幼儿细支气管炎和病毒性肺炎的主要病因。目前尚无预防 RSV 感染的疫苗,但可预防性给予病毒中和单克隆抗体,这强调了抗体的保护潜力。RSV 疫苗学的一个概念是母亲免疫接种以诱导高抗体滴度,从而通过胎盘将高水平的母体抗体被动转移给胎儿,并通过初乳将抗体转移给新生儿。棉鼠是 RSV 感染的优秀小动物模型,已被用于测试母体免疫接种。为了在棉鼠模型中从机制上了解抗体转移,我们对棉鼠胎盘和 Fc 受体定位进行了表征。从中孕期(约第 14 天)、晚孕期(约第 25 天)和新生(小于 1 周)棉鼠的胎盘中收集胃肠道组织进行光镜、免疫组织化学和透射电子显微镜检查。棉鼠胎盘呈血绒毛膜型,有 5 个不同的层:蜕膜、连接区、绒毛膜、绒毛膜板和卵黄囊。与母体抗体的转移一致,大多数 Fc 受体存在于卵黄囊内胚层和绒毛膜板的胎儿毛细血管内皮中,涉及绒毛膜中 10%的细胞。此外,棉鼠的十二指肠和空肠肠上皮细胞也存在 Fc 受体,与人类、小鼠和大鼠相似。这些发现为棉鼠中描述的母体抗体的产前和产后转移提供了结构基础。