Nonhuman Primate Model of Pertussis
Nonhuman Primate Model of Pertussis
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DOI：
10.1128/iai.06310-11
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发表时间：
2012-04-01
影响因子：
3.1
通讯作者：
Merkel, Tod J.
中科院分区：
文献类型：
--
作者：
Warfel, Jason M.;Beren, Joel;Merkel, Tod J.
百日咳是一种高度传染性的急性呼吸道疾病，由细菌病原体百日咳博德特氏菌引起。尽管几乎普及了疫苗，但在过去20年中，美国的百日咳发病率一直在稳步上升。我们未能理解和应对这一重要的公共卫生问题，在很大程度上是由于我们对这种疾病和疫苗介导的保护机制的认识存在差距。由于缺乏复制人类疾病全谱的动物模型，有关百日咳发病机制和疫苗有效性机制的重要问题仍未得到解答。由于目前的动物模型不能满足这些需求，我们着手开发一种非人灵长类百日咳模型。我们用野生型B接种恒河猴和橄榄狒狒。百日咳菌株和评估动物的临床疾病。我们发现只有25%的恒河猴患上百日咳。相比之下，100%接种的狒狒出现临床百日咳。当恢复期狒狒从原发性感染中恢复后6个月被感染时，观察到强烈的回忆反应。我们的研究结果表明，狒狒提供了一个很好的临床百日咳模型，这将使研究人员能够研究百日咳的发病机制和疾病进展，评估目前获得许可的疫苗，并开发改进的疫苗和治疗方法。
Pertussis is a highly contagious, acute respiratory illness caused by the bacterial pathogen Bordetella pertussis. Despite nearly universal vaccine coverage, pertussis rates in the United States have been rising steadily over the last 20 years. Our failure to comprehend and counteract this important public health concern is due in large part to gaps in our knowledge of the disease and the mechanisms of vaccine-mediated protection. Important questions about pertussis pathogenesis and mechanisms of vaccine effectiveness remain unanswered due to the lack of an animal model that replicates the full spectrum of human disease. Because current animal models do not meet these needs, we set out to develop a nonhuman primate model of pertussis. We inoculated rhesus macaques and olive baboons with wild-type B. pertussis strains and evaluated animals for clinical disease. We found that only 25% of rhesus macaques developed pertussis. In contrast, 100% of inoculated baboons developed clinical pertussis. A strong anamnestic response was observed when convalescent baboons were infected 6 months following recovery from a primary infection. Our results demonstrate that the baboon provides an excellent model of clinical pertussis that will allow researchers to investigate pertussis pathogenesis and disease progression, evaluate currently licensed vaccines, and develop improved vaccines and therapeutics.