Battelle Biomedical Research Center, 505 King Ave., Columbus, OH 43201, USA.
Microb Pathog. 2011 Jan;50(1):12-22. doi: 10.1016/j.micpath.2010.10.002. Epub 2010 Oct 30.
A recombinant vaccine (rF1V) is currently being developed for protection against pneumonic plague. An essential component in evaluating efficacy of the rF1V vaccine is the development of a well-understood animal model that shows similarity to human disease. The objective of this study was to determine the inhaled median lethal dose (LD₅₀), evaluate the pathophysiology of disease and identify appropriate study endpoints in a cynomolgus macaque (CM) model of pneumonic plague. Eighteen CMs were challenged by head-only aerosol exposure with seven dosages of Yersinia pestis CO92. An LD₅₀ of 24 colony forming units was estimated using Probit analysis. Disease pathology was evaluated by blood culture, clinical pathology, histopathology and telemetry. CMs that died became febrile following challenge and died 34-92 h after onset of fever. Bacteremia, increased respiration and heart rate, decreased blood pressure and loss of diurnal rhythm were also observed in conjunction with onset of fever. Histopathological examinations revealed significant findings in the lungs (intra-alveolar neutrophils and fibrinous pleuritis) consistent with pneumonic plague. These data indicate that the disease pathology observed in CMs following aerosol exposure to Y. pestis CO92 is similar to that of pneumonic plague in humans. Thus, the CM is an appropriate model to evaluate efficacy of a recombinant F1V vaccine candidate.
一种针对肺鼠疫的重组疫苗（rF1V）目前正在开发中。评估 rF1V 疫苗功效的一个重要组成部分是开发一种对人类疾病具有相似性的、充分了解的动物模型。本研究的目的是确定吸入性半数致死剂量（LD₅₀），评估疾病的病理生理学，并确定在肺鼠疫食蟹猴（CM）模型中适当的研究终点。18 只 CM 通过头部气溶胶暴露接受了七种剂量的鼠疫耶尔森氏菌 CO92 的挑战。使用 Probit 分析估计 LD₅₀为 24 个集落形成单位。通过血培养、临床病理学、组织病理学和遥测来评估疾病病理。在挑战后，死亡的 CM 变得发热，并在发热开始后 34-92 小时死亡。还观察到菌血症、呼吸和心率增加、血压下降以及昼夜节律丧失与发热同时发生。组织病理学检查显示，CM 肺部出现与肺鼠疫一致的明显病变（肺泡内中性粒细胞和纤维性胸膜炎）。这些数据表明，CM 在用 Y. pestis CO92 气溶胶暴露后观察到的疾病病理与人类肺鼠疫相似。因此，CM 是评估重组 F1V 疫苗候选物功效的合适模型。
