Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&M University, Bryan, Texas, USA.
Tulane University, School of Medicine, Tulane National Primate Research Center, Covington, Louisiana, USA.
Infect Immun. 2019 Nov 18;87(12). doi: 10.1128/IAI.00178-19. Print 2019 Dec.
, the etiological agent of Q fever, is a Gram-negative bacterium transmitted to humans by inhalation of contaminated aerosols. Acute Q fever is often self-limiting, presenting as a febrile illness that can result in atypical pneumonia. In some cases, Q fever becomes chronic, leading to endocarditis that can be life threatening. The formalin-inactivated whole-cell vaccine (WCV) confers long-term protection but has significant side effects when administered to presensitized individuals. Designing new vaccines against remains a challenge and requires the use of clinically relevant modes of transmission in appropriate animal models. We have developed a safe and reproducible aerosol challenge in three different animal models to evaluate the effects of pulmonary acquired infection. Using a MicroSprayer aerosolizer, BL/6 mice and Hartley guinea pigs were infected intratracheally with Nine Mile phase I (NMI) and demonstrated susceptibility as determined by measuring bacterial growth in the lungs and subsequent dissemination to the spleen. Histological analysis of lung tissue showed significant pathology associated with disease, which was more severe in guinea pigs. Infection using large-particle aerosol (LPA) delivery was further confirmed in nonhuman primates, which developed fever and pneumonia. We also demonstrate that vaccinating mice and guinea pigs with WCV prior to LPA challenge is capable of eliciting protective immunity that significantly reduces splenomegaly and the bacterial burden in spleen and lung tissues. These data suggest that these models can have appreciable value in using the LPA delivery system to study pulmonary Q fever pathogenesis as well as designing vaccine countermeasures to aerosol transmission.
Q 热的病原体，贝氏柯克斯体，是一种革兰氏阴性细菌，通过吸入受污染的气溶胶传播给人类。急性 Q 热通常是自限性的，表现为发热性疾病，可导致非典型肺炎。在某些情况下，Q 热会变成慢性，导致可能危及生命的心内膜炎。甲醛灭活全细胞疫苗（WCV）可提供长期保护，但在给预致敏个体接种时会产生明显的副作用。设计针对 的新疫苗仍然是一个挑战，需要在适当的动物模型中使用临床相关的传播方式。我们已经开发了三种不同动物模型中的安全且可重复的 气溶胶挑战，以评估肺获得性感染的影响。使用 MicroSprayer 气溶胶发生器，BL/6 小鼠和 Hartley 豚鼠经气管内感染 9 英里一期（NMI），通过测量肺部细菌生长和随后向脾脏的传播来确定其易感性。肺组织的组织学分析显示与疾病相关的显著病理学，在豚鼠中更为严重。使用大颗粒气溶胶（LPA）输送的感染在非人类灵长类动物中进一步得到证实，这些动物出现发热和肺炎。我们还证明，在用 LPA 挑战之前用 WCV 对小鼠和豚鼠进行疫苗接种能够引起保护性免疫，显著减少脾肿大以及脾脏和肺部组织中的细菌负荷。这些数据表明，这些模型在使用 LPA 输送系统研究肺 Q 热发病机制以及设计针对气溶胶传播的疫苗对策方面具有相当的价值。
