10th International Aerosol Conference September 2 - September 7, 2018 America's Center Convention Complex St. Louis, Missouri, USA
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Exposure of Cynomolgus Macaques To Small Particle Aerosols Containing H5N1 Avian Influenza Triggers Rapid, Lethal Acute Respiratory Distress Syndrome
DOUGLAS REED, Elizabeth Wonderlich, Katherine O' Malley, Jennifer Bowling, Amy Hartman, Jonathan Carney, Charles Scanga, Daniel Perez, Simon Barratt-Boyes, University of Pittsburgh
Abstract Number: 576 Working Group: Infectious Bioaerosol
Abstract Avian influenza viruses including H5N1 and H7N9 can trigger severe, often fatal disease in humans. Severe viral pneumonia caused by H5N1 or H7N9 is thought to be a lower respiratory tract disease whereas seasonal influenza is a upper respiratory tract disease. Intratracheal and/or intranasal inoculation of virus only rarely results in severe, lethal disease in cynomolgus macaques. We developed a system for aerosol exposure of macaques to a highly pathogenic avian influenza virus, H5N1 (A/Vietnam/1203/2004). Macaques were exposed in a head-only chamber side a class III biological safety cabinet in the regional biocontainment laboratory at ABSL-3+. Aerosols were generated with an Aeroneb vibrating mesh nebulizer (Aerogen, Deerfield, IL) controlled by the AeroMP aerosol exposure system (Biaera Technologies, Hagerstown, MD). Aerosol sampling was accomplished using an all-glass impinger (Ace Glass, Vineland, NJ) and Aerodynamic Particle Sizer (TSi, Inc, Shoreview, MD). Initial studies prior to macaque exposures demonstrated that for virus aerosols the Aeroneb was consistently superior to the Collison 3-jet as measured by spray factor. Relative to fluorescein, there was little or no loss of influenza with the Aeroneb compared to a >90% loss of influenza with the Collison 3-jet nebulizer. Particle sizes generated by the Aeroneb were in the respirable range that would reach the deep lung. Within 18 hours of infection, macaques were febrile and there were significant changes in respiratory function which worsened on days 2 and 3. PET/CT imaging at 48 hours revealed a considerable inflammatory response in the lung. Mean time to death was 72 hours post-infection. Pathological and clinical findings all suggest the cause of death is acute respiratory distress syndrome (ARDS) which strongly represents what is seen in humans. Even at aerosol doses 10-fold lower than had previously been reported for other routes of inoculation, the disease was rapid and fatal in macaques. This new nonhuman primate model will be useful for developing and testing new vaccine or therapeutic approaches to treat severe human disease caused by avian influenza viruses.