Affiliation:
1. Lovelace Respiratory Research Institute, Albuquerque, New Mexico
2. Public Health Research Institute at the International Center for Public Health, NJMS-UMDNJ, Newark, New Jersey
3. Departments of Pathology and Internal Medicine, University of New Mexico Health Science Center, Albuquerque, New Mexico
Abstract
ABSTRACT
Vaccines against primary pneumonic plague, a potential bioweapon, must be tested for efficacy in well-characterized nonhuman primate models. Telemetered cynomolgus macaques (
Macaca fascicularis
) were challenged by the aerosol route with doses equivalent to approximately 100 50% effective doses of
Yersinia pestis
strain CO92 and necropsied at 24-h intervals postexposure (p.e.). Data for telemetered heart rates, respiratory rates, and increases in the temperature greater than the diurnal baseline values identified the onset of the systemic response at 55 to 60 h p.e. in all animals observed for at least 70 h p.e. Bacteremia was detected at 72 h p.e. by a
Yersinia
16S rRNA-specific quantitative reverse transcription-PCR and was detected later by the culture method at the time of moribund necropsy. By 72 h p.e. multilobar pneumonia with diffuse septal inflammation consistent with early bacteremia was established, and all lung tissues had a high bacterial burden. The levels of cytokines or chemokines in serum were not significantly elevated at any time, and only the interleukin-1β, CCL2, and CCL3 levels were elevated in lung tissue. Inhalational plague in the cynomolgus macaque inoculated by the aerosol route produces most clinical features of the human disease, and in addition the disease progression mimics the disease progression from the anti-inflammatory phase to the proinflammatory phase described for the murine model. Defined milestones of disease progression, particularly the onset of fever, tachypnea, and bacteremia, should be useful for evaluating the efficacy of candidate vaccines.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Reference22 articles.
1. Adamovicz, J. J., and P. L. Worsham. 2006. Plague, p. 107-135. In J. Swearengen (ed.), Biodefense research methodology and animal models. Taylor & Francis, Boca Raton, FL.
2. Bosio, C. M., A. W. Goodyear, and S. W. Dow. 2005. Early interaction of Yersinia pestis with APCs in the lung. J. Immunol.175:6750-6756.
3. Delayed Inflammatory Response to Primary Pneumonic Plague Occurs in Both Outbred and Inbred Mice
4. Cheng, Y. S., H. Irshad, P. Kuehl, T. D. Holmes, R. Sherwood, and C. H. Hobbs. 2008. Lung deposition of droplet aerosols in monkeys. Inhal. Toxicol.20:1029-1036.
5. Cohen, R. J., and J. L. Stockard. 1967. Pneumonic plague in an untreated plague-vaccinated individual. JAMA202:365-366.
Cited by
27 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献