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Accelerated onset of chronic wasting disease in elk (Cervus canadensis) vaccinated with a PrPSc-specific vaccine and housed in a prion contaminated environment
Institution:1. Wyoming Game and Fish Department, 1212 South Adams St, Laramie, WY, USA;2. Vaccine and Infectious Disease Organization-International Vaccine Research Center, University of Saskatchewan, 120 Veterinary Road, S7N 5E3 Saskatoon, Saskatchewan, Canada;3. School of Public Health, University of Saskatchewan, 104 Clinic Place, S7N 2Z4 Saskatoon, Saskatchewan, Canada;4. Wyoming Game and Fish Department, Thorne-Williams Wildlife Research Center, 2362 HWY 34 Wheatland, WY, USA;5. Department of Neurology, University of British Columbia, S192 – 2211 Wesbrook Mall, V6T 2B5 Vancouver, BC, Canada;6. Pan-Provincial Vaccine Enterprise Inc. University of Saskatchewan, 120 Veterinary Road, S7N 5E3 Saskatoon, Saskatchewan, Canada;7. Department of Biochemistry, University of Saskatchewan, 107 Wiggins Road, S7N 5E5 Saskatoon, Saskatchewan, Canada;1. Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, Department of Laboratory Medicine, The First Affiliated Hospital, China Medical University, Shenyang 110001, China;2. Key Laboratory of AIDS Immunology of Liaoning Province, Shenyang 110001, China;3. Comprehensive AIDS Research Center, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084,China;4. Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China;5. Key Laboratory of AIDS Immunology, Chinese Academy of Medical Sciences, Shenyang 110001, China
Abstract:Chronic wasting disease (CWD) is a fatal prion disease affecting multiple cervid species. Effective management tools for this disease, particularly in free-ranging populations, are currently limited. We evaluated a novel CWD vaccine in elk (Cervus canadensis) naturally exposed to CWD through a prion-contaminated environment. The vaccine targets a YYR disease-specific epitope to induce antibody responses specific to the misfolded (PrPSc) conformation. Female elk calves (n = 41) were captured from western Wyoming and transported to the Thorne-Williams Wildlife Research Center where CWD has been documented since 1979. Elk were held in contaminated pens for 14 to 20 days before being alternately assigned to either a vaccine (n = 21) or control group (n = 20). Vaccinated animals initially received two vaccinations approximately 42 days apart and annual vaccinations thereafter. Vaccination induced elevated YYR-specific antibody titers in all animals. Elk were genotyped for the prion protein gene at codon 132, monitored for clinical signs of CWD through daily observation, for disease status through periodic biopsy of rrectoanal mucosa-associated lympoid tissue (RAMALT), and monitored for YYR-specific serum antibody titres. Mean survival of vaccinated elk with the 132MM genotype (n = 15) was significantly shorter (800 days) than unvaccinated elk (n = 13) of the same genotype (1062 days; p = 0.003). Mean days until positive RAMALT biopsy for 132MM vaccinated elk (6 7 8) were significantly shorter than unvaccinated 132MM elk (990; p = 0.012). There was, however, no significant difference in survival between vaccinated (n = 4) and control (n = 5) elk with the 132ML genotype (p = 0.35) or in timing of positive RAMALT biopsies of 132ML elk (p = 0.66). There was no strong (p = 0.17) correlation between YYR-specific antibody titers and survival time. Determining the mechanism by which this vaccine accelerates onset of CWD will be important to direct further CWD vaccine research.
Keywords:Cervus canadensis  Chronic wasting disease  CWD  Elk  Prion  Vaccine
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