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布鲁氏菌属羊种经气管内接种孕豚鼠是研究生殖发病机制和疫苗的改良模型。

Intratracheal Inoculation with Brucella melitensis in the Pregnant Guinea Pig Is an Improved Model for Reproductive Pathogenesis and Vaccine Studies.

机构信息

Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, USA.

Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&M University, College Station, Texas, USA.

出版信息

Infect Immun. 2020 Sep 18;88(10). doi: 10.1128/IAI.00204-20.

DOI:10.1128/IAI.00204-20
PMID:32690632
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7504952/
Abstract

Reproductive failure is the hallmark of brucellosis in animals. An uncommon but important complication in pregnant women who become acutely infected with is spontaneous pregnancy loss or vertical transmission to the fetus. Unfortunately, the mechanism behind reproductive failure is still obscure, partially due to the lack of a proper study model. Recently, it was demonstrated that intratracheal (IT) inoculation of nonpregnant guinea pigs would replicate features of clinical disease in humans. To determine if IT inoculation would induce reproductive disease, guinea pigs were infected at mid-gestation and monitored daily for fever and abortions. Fever developed between day 14 to 18 postinoculation, and by 3 weeks postinoculation, 75% of pregnant guinea pigs experienced stillbirths or spontaneous abortions mimicking natural disease. Next, to investigate the guinea pig as a model for evaluating vaccine efficacy during pregnancy, nonpregnant guinea pigs were vaccinated with S19, 16MΔ + Quil-A, or 100 μl PBS + Quil-A (as control). Guinea pigs were bred and vaccinated guinea pigs were challenged at mid-gestation with IT inoculation and monitored for fever and abortions. Vaccination with both vaccines prevented fever and protected against abortion. Together, this study indicates that pregnant guinea pigs are an appropriate animal model to study reproductive disease and offer an improved model to evaluate the ability of vaccine candidates to protect against a serious manifestation of disease.

摘要

生殖失败是动物布鲁氏菌病的标志。孕妇急性感染后会出现自发性流产或垂直传播给胎儿,这是一种不常见但很重要的并发症。不幸的是,生殖失败的机制仍不清楚,部分原因是缺乏适当的研究模型。最近,研究表明向未怀孕的豚鼠气管内(IT)接种可复制人类临床疾病的特征。为了确定 IT 接种是否会引起生殖疾病,在妊娠中期对豚鼠进行感染,并每天监测其发热和流产情况。接种后第 14 至 18 天出现发热,接种后 3 周时,75%的怀孕豚鼠发生死产或自然流产,类似于自然疾病。接下来,为了研究豚鼠作为评估妊娠期疫苗效力的模型,用 S19、16MΔ+Quil-A 或 100 μl PBS+Quil-A(对照)对未怀孕的豚鼠进行疫苗接种。然后对豚鼠进行繁殖,并在妊娠中期用 IT 接种对已接种疫苗的豚鼠进行攻毒,监测其发热和流产情况。两种疫苗均可预防发热并防止流产。综上所述,该研究表明怀孕豚鼠是研究生殖疾病的合适动物模型,并提供了一种改进的模型来评估疫苗候选物预防严重疾病表现的能力。