Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, FDA, Bethesda, Maryland, USA.
Infect Immun. 2012 Apr;80(4):1530-6. doi: 10.1128/IAI.06310-11. Epub 2012 Jan 17.
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.
百日咳是由细菌病原体百日咳博德特氏菌引起的高度传染性急性呼吸道疾病。尽管几乎普遍接种了疫苗,但在美国,百日咳的发病率在过去 20 年中一直在稳步上升。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该病和疫苗介导的保护机制的认识存在差距。由于缺乏能够复制人类疾病全貌的动物模型,关于百日咳发病机制和疫苗有效性的重要问题仍未得到解答。由于当前的动物模型无法满足这些需求,我们着手开发一种非人类灵长类动物的百日咳模型。我们用野生型百日咳博德特氏菌菌株对恒河猴和狒狒进行了接种,并对动物的临床疾病进行了评估。我们发现只有 25%的恒河猴发生了百日咳。相比之下,100%的接种狒狒出现了临床百日咳。在从初次感染中康复 6 个月后再次感染时,康复的狒狒出现了强烈的回忆性反应。我们的结果表明,狒狒提供了一个极好的临床百日咳模型,将使研究人员能够研究百日咳的发病机制和疾病进展,评估目前许可的疫苗,并开发出改进的疫苗和疗法。