Reading Room Production — page 411

AAI18027-001-00000 pg. 2 Scope of Work: NIAID is developing Medical Countermeasures (MCMs) to protect against Ebola virus disease. Therefore, NIAID needs to understand differences in disease when Ebola virus infection occurs by different routes and to ensure that MCMs under development are effective in these different scenarios. The purpose of this study is to further understand the disease caused by aerosolized Ebola virus in a relevant animal model. This study has been developed jointly by NIAID and the National Biological Threat Characterization Center (NBTCC) in coordination with DHS/S&T BTCP. NBTCC shall perform work on a non-interference basis with DHS/S&T priorities and the NBACC Annual Plan. Under this work plan, the NBTCC with guidance from the BTCP shall: (1) NBTCC shall conduct pre-execution activities to obtain all necessary approvals to conduct the project (2) NBTCC shall provide NIAID and BTCP a draft study protocol for the in vitro study and a final study protocol following incorporation of NIAID and BTCP input. NBTCC shall first assess their inhalation exposure system with Ebola virus and optimize aerosol generation, sampling, and assay methodologies. The target median aerodynamic particle sizes will be 1-3 μm, to allow comparison to previously published studies with aerosolized filoviruses which utilized small particle aerosols to facilitate penetration to the deep lung, and 10-12 μm, to facilitate deposition in the oronasal region of the upper respiratory tract. (3) NBTCC shall provide NIAID (4) and BTCP a draft study protocol for the small particle study and a final study protocol following incorporation of NIAID and BTCP input. Conduct studies to determine the influence of Ebola virus aerodynamic 1-3 μm particle sizes on the median lethal dose and disease presentation in a nonhuman primate (NHP) model of inhalational Ebola virus disease (EVD). They shall assess the median lethal dose of Ebola virus small particle aerosols in NHPs using a modified up-and-down methodology. NBTCC estimates that approximately 24 NHPs will be required for each experiment. (5) NBTCC shall provide NIAID and BTCP a draft study protocol for the large particle study and a final study protocol following incorporation of NIAID and BTCP input. Conduct studies to determine the influence of Ebola virus aerodynamic 10-12 μm particle sizes on the median lethal dose and disease presentation in a nonhuman primate (NHP) model of inhalational Ebola virus disease (EVD). They shall assess the median lethal dose of Ebola virus small particle aerosols in NHPs using a modified up-and-down methodology. NBTCC estimates that approximately 24 NHPs will be required for each experiment. (6) NBTCC shall provide NIAID and BTCP a draft study report, host a NIAID and BTCP audit and then provide a final report addressing and incorporating NIAID and BTCP comments and feedback Under this work plan, NIAID will: • Fund this work. NIAID personnel will provide feedback on draft study protocols for NBTCC to incorporate into final study protocols. NIAID personnel will also review the study report and perform an audit of the draft study report and raw data.