1732. A Canine Target Species Challenge Model to Evaluate Efficacy of a Coccidioidomycosis Vaccine

BACKGROUND: The preferred efficacy design for licensing a vaccine for animal use (United States Department of Agriculture (USDA)) is a prospective, placebo-controlled, randomized, and double-blinded vaccination-challenge trial. In such studies, each subject receives the same exposure to the virulent pathogen by active challenge. To test a cps1, live avirulent canine coccidioidomycosis vaccine, an inhalation disease model was developed in beagle dogs. METHODS: 6-month old male beagle dogs were housed according to PHS standards. All procedures, approved by the Institutional Animal Care and Use Committee for Colorado State University, were performed at ABSL3. Dogs were infected by nebulization with low, medium or high counts of arthroconidia of Coccidioides posadasii, strain Silveira, delivered via endotracheal tube under injectable anesthesia. Thoracic radiographs, CBC, and serum chemistries and body weights were obtained at 2- or 3-week intervals and dogs were euthanized 8 weeks p.i., or earlier if necessary. Approximately 1 gram lung specimens from each lobe were cultured for fungal burden. Fixed tissues were examined histologically. Serum was tested for antibodies. RESULTS: Ten of 11 dogs were successfully infected; 5 required early removal at 33 to 48-days p.i. Elevated globulin, decreased albumin, decreased A/G ratio, monocytosis and weight loss were present in all infected dogs. Radiographic and histopathological lesions were very extensive at the high challenge doses. Medium doses had the most consistent scoring and clinical findings, including some early removal, without overwhelming disease, while the low dose produced the least consistent quantifiable features. All dogs developed antibodies. CONCLUSION: Nebulized aerosol delivery of spores reproducibly produced significant coccidioidomycosis in 10 of 11 dogs. Overall, the challenge model demonstrated consistent characteristic findings sufficient to assess vaccine efficacy in dogs during an 8-week period post challenge without producing a potentially overwhelming infection. The aerosol nebulization of arthroconidia in beagle dogs should provide a vaccination-challenge experimental design in line with Chapter 9 Code of Federal Regulations, parts 102.5 and 104.5. DISCLOSURES: All authors: No reported disclosures.