American Association for Aerosol Research - Abstract Submission

AAAR 33rd Annual Conference
October 20 - October 24, 2014
Rosen Shingle Creek
Orlando, Florida, USA

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Non-Human Primate Model Development Using Large Particle Aerosolized Cowpox Virus

MATTHEW LACKEMEYER, Kyle Bohannon, Amy Papaneri, Gary Sparks, Reed Johnson, Peter Jahrling, NIAID

     Abstract Number: 553
     Working Group: Bioaerosols

Abstract
Zoonotic orthopoxvirus infections continue to be a threat to public health in numerous countries. For instance, cowpox and monkeypox viruses are endemic in Europe and Africa, respectively, where they have caused repeated human infections, sometimes with grave consequences. In addition, orthopoxviruses are considered possible starting materials for the construction of biological weapons. To improve public-health preparedness and medical countermeasure development, well characterized nonhuman primate models need to be established for human orthopoxvirus infections. Aerosolization represents the most natural route of infection for orthopoxviruses and would also be the most likely route of infection during an intentional biological attack. For countermeasure licensure, the US Food and Drug Administration (FDA) asks for drug evaluation in animal models that mimic the natural course of the targeted disease, including infection route. Aerosol particle size and respiratory tract deposition play a key role in disease course, presentation, and time to death. In general, aerosol generation of small particles (<3 micro-meters) penetrate deep within the alveolar region, whereas aerosolization of large particles (7-11 micro-meters) move within the nasopharyngeal region, depositing within the nose, mouth, pharynx, and larynx. Particles that are intermediate in size (3-6 micro-meters) will deposit within the tracheobronchial region. Controlling the particle size and evaluating the site of infection will further refine the development of aerosol nonhuman primate models for orthopoxvirus infections and thus facilitate medical countermeasure development. We previously established a small-particle cowpox virus aerosol exposure model, which unfortunately did not mimic human disease. Here we present the results of a similar study in rhesus monkeys challenged with four distinct large particle aerosols.