Y. pestis Murine Bioaerosol Animal Model for plague

Yersinia pestis, a Gram-negative bacterium, is the causative agent for bubonic and pneumonic plague. Y. pestis is a potential bioterrorism agent when released as an aerosol, due to its characteristic rapidly progressing symptoms and high mortality rate following inhalation infection. Although pneumonic plague is treatable with antibiotics, treatment must be administered shortly after exposure. With the emergence of antibiotic-resistant strains, interest remains high in the development of new vaccines or therapeutics as medical countermeasures (MCMs) for aerosolized Y. pestis.

Aerosol Generation System

For reproducible aerosol exposure in animal challenge studies, a reliable and robust aerosol generation system is required. IITRl’s proprietary, nose-only aerosol generation system has proven to be highly effective in generating and stabilizing aerosolized bacteria for inhalation infection in vaccine or antimicrobial challenge studies in rodents and rabbits. The system’s ability to deliver a high concentration of viable challenge material to each target animal has been demonstrated across a wide range of starting culture concentrations, see Figure 1 below.

The spray factor for Y. pestis (viable aerosol concentration / inoculum concentration) was shown to be 1.4 x 10-5; this spray factor value was stable over multiple runs and across 105 to 109 CFU/mL inoculum concentrations for Swiss Webster mice with an LD50 of 2000 CFU. Published results using this system can be found in these papers: P. Fellows, et al, Vaccine 28(49):7748-56 (2010) and P. Fellows, W. Lin, et al, 19(4), 468-476 (2012).

Figure 1: Comparison of Spray Factors over Several Concentrations of Y. pestis

Lethal Mouse Model for Aerosolized Y. pestis in BALB/c mice

IITRI has also developed and characterized a BALB/c murine model for pneumonic plague using the nose-only aerosol generation and exposure system for aerosol challenge studies using Y. pestis. BALB/c mice were infected with aerosolized Y. pestis CO92 in a series of exposure concentrations similar to the model developed with Swiss Webster mice. In the survival curve shown in Figure 2, a direct dose/mortality relationship was shown for the BALB/c mouse model. The LD50 was determined to be 8060 CFU/animal.

Figure 2. Survival of BALB/c Mice at Different Exposure Concentrations of Y. pestis

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