The incidence of primary pulmonary infections for most of the major biothreats is extremely low. Therefore, we will not be able to rely on testing new therapeutics and vaccines during "natural" outbreaks as is commonly done for many more common infections. Further, as is the case with the human immunodeficiency virus, direct challenges with the biothreats in normal human populations is unlikely to be a viable alternative. Because of these issues we will need to rely on animal models much more than usual for understanding the basic pathophysiology of the disease as well as determining the efficacy of new therapeutics and vaccines. The development of well-characterized nonhuman primate models that recapitulate human disease is extremely important to NIH's mission of biodefense. The combination of UNM and LRRI brings together significant expertise that makes this core very unique in its capabilities. The PI of this program project, Dr. Lyons, at UNMHSC has handled the biothreats for over 2 years and developed all of the protocols and safety requirements for appropriate handling and management of the select agents including Bacillus anthracis and virulent Francisella tularensis. This proposal intends to use both mice and nonhuman primates to identify mechanisms of virulence and host protection. It will combine the strengths in UNMHSC Microbiology with the aerosol and primate expertise of Lovelace Respiratory Research Institute. Specifically the non-human primate core will: 1) Develop reproducible aerosol models in non-human primates for virulent Francisella tularensis and Bacillus anthracis. 2) Perform aerosol challenges, necropsy and tissue harvesting for the aims in Project 1 and 3.