Faculty of Medicine and Institute for Life Sciences, University of Southampton, Academic Unit of Clinical Experimental Sciences, NIHR Clinical Research Facility and NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Mailpoint 218, University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton, SO16 6YD, UK.
Curr Top Microbiol Immunol. 2024;445:155-175. doi: 10.1007/82_2022_260.
Bordetella pertussis, a slow-growing Gram-negative coccobacillus and the causative agent of whooping cough, is one of the leading causes of vaccine-preventable death and morbidity globally. A state of asymptomatic human carriage has not yet been demonstrated by population studies but is likely to be an important reservoir for community transmission of infection. Such a carriage state may be a target for future vaccine strategies. This chapter presents a short summary of the characteristics of B. pertussis, which should be taken into account when developing a human challenge model and any future experimental medicine interventions. Three studies involving deliberate infection with B. pertussis have been described to date. The first of these was a scientifically and ethically unacceptable paediatric challenge study involving four children in 1930. The second was an investigation of a putative live vaccine using a genetically modified and attenuated strain of B. pertussis. Finally, a systematically constructed human challenge model using a wild-type, potentially pathogenic strain has been established. The latter study has demonstrated that deliberate induction of asymptomatic colonisation in humans is safe and immunogenic, with colonised participants exhibiting seroconversion to pertussis antigens. It has also shown nasal wash to be a more sensitive method of detecting the presence of B. pertussis than either pernasal swab or throat swab, and that B. pertussis carriage can be cleared effectively with Azithromycin. The development of this wild-type B. pertussis human challenge model will allow the investigation of host-pathogen and facilitate future vaccine development.
百日咳博德特氏菌是一种生长缓慢的革兰氏阴性球杆菌，也是百日咳的病原体，它是全球可通过疫苗预防的死亡和发病的主要原因之一。人群研究尚未证明存在无症状人类带菌状态，但这种状态很可能是社区传播感染的重要储主。这种带菌状态可能是未来疫苗策略的目标。本章简要介绍了百日咳博德特氏菌的特征，在开发人体挑战模型和任何未来的实验医学干预措施时都应考虑这些特征。迄今为止，已经描述了三项涉及故意感染百日咳博德特氏菌的研究。第一项研究是 1930 年涉及四名儿童的科学和伦理上不可接受的儿科挑战研究。第二项是使用基因修饰和减毒的百日咳博德特氏菌菌株对疑似活疫苗的调查。最后，建立了一个使用野生型、潜在致病性菌株的系统构建的人体挑战模型。后一项研究表明，在人类中故意诱导无症状定植是安全且具有免疫原性的，定植参与者对百日咳抗原产生血清转化。它还表明，鼻洗液比经鼻拭子或咽拭子更能敏感地检测到百日咳博德特氏菌的存在，并且阿奇霉素可有效清除百日咳博德特氏菌的定植。这种野生型百日咳博德特氏菌人体挑战模型的发展将允许对宿主-病原体进行研究，并有助于未来的疫苗开发。
