4.1. Animals and Ethical Statement

Twenty-eight healthy, adult female and male cynomolgus macaques (Macaca fascicularis) of primarily Chinese descent weighing between 3.6 kg and 7.4 kg were obtained from USAMRIID NHP colony. The age of the animals ranged from 3 years to 7 years. Animals were experimentally naïve with the exception of four animals that were either previously used as negative controls or survived a previous challenge with Francisella tularensis SCHU S4 and had a calculated exposure dose of 0 CFU with no signs of the disease and no antibodies against F. tularensis. Animals were in good physical condition, lacked physical malformations, and were free of clinical signs of infectious, contagious, or communicable diseases or parasites. All animals exposed to F. tularensis were handled in a BSL-3 containment laboratory at the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID). Research was conducted in compliance with the Animal Welfare Act and other federal statutes and regulations relating to animals and experiments involving animals, and adhered principles stated in the Guide for the Care and Use of Laboratory Animals, National Research Council, 1996. The facility where this research was conducted (USAMRIID) is fully accredited by the Association for the Assessment and Accreditation of Laboratory Animal Care International. Research was conducted under a protocol approved by the Institutional Animal Care and Use Committee (IACUC) at USAMRIID. All animals were examined and evaluated twice per day by study personnel. Early endpoint criteria, as specified by the score parameters within the “Post-exposure observations” section of these methods, were used to determine when animals should be humanely euthanized.