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Cynomolgus macaque model for pneumonic plague.
MedLine Citation:
PMID:  21040776     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
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.
Authors:
Richard Warren; Hank Lockman; Roy Barnewall; Robert Krile; Oscar Bermeo Blanco; Daphne Vasconcelos; Jessica Price; Robert V House; Mark A Bolanowksi; Patricia Fellows
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-30
Journal Detail:
Title:  Microbial pathogenesis     Volume:  50     ISSN:  1096-1208     ISO Abbreviation:  Microb. Pathog.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-03     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8606191     Medline TA:  Microb Pathog     Country:  England    
Other Details:
Languages:  eng     Pagination:  12-22     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Ltd. All rights reserved.
Affiliation:
Battelle Biomedical Research Center, 505 King Ave., Columbus, OH 43201, USA.
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