Accelerated onset of chronic wasting disease in elk (Cervus canadensis) vaccinated with a PrP Sc -specific vaccine and housed in a prion contaminated environment Mary E. Wood a,d,⇑ , Philip Griebel b,c , Matthew L. Huizenga d , Samuel Lockwood d , Cole Hansen d , Andrew Potter b , Neil Cashman e , John W. Mapletoft f , Scott Napper b,g a Wyoming Game and Fish Department, 1212 South Adams St, Laramie, WY, USA b Vaccine and Infectious Disease Organization-International Vaccine Research Center, University of Saskatchewan, 120 Veterinary Road, S7N 5E3 Saskatoon, Saskatchewan, Canada c School of Public Health, University of Saskatchewan, 104 Clinic Place, S7N 2Z4 Saskatoon, Saskatchewan, Canada d Wyoming Game and Fish Department, Thorne-Williams Wildlife Research Center, 2362 HWY 34 Wheatland, WY, USA e Department of Neurology, University of British Columbia, S192 – 2211 Wesbrook Mall, V6T 2B5 Vancouver, BC, Canada f Pan-Provincial Vaccine Enterprise Inc. University of Saskatchewan, 120 Veterinary Road, S7N 5E3 Saskatoon, Saskatchewan, Canada g Department of Biochemistry, University of Saskatchewan, 107 Wiggins Road, S7N 5E5 Saskatoon, Saskatchewan, Canada article info Article history: Received 3 July 2018 Received in revised form 7 October 2018 Accepted 14 October 2018 Available online xxxx Keywords: Cervus canadensis Chronic wasting disease CWD Elk Prion Vaccine 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 (PrP Sc ) 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 alter- nately 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 peri- odic 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 signifi- cantly 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. Published by Elsevier Ltd. 1. Introduction Chronic wasting disease (CWD) is a fatal prion disease affecting multiple cervid species. The molecular basis of the disease is the misfolding of functional prion protein (PrP C ) into an infectious and pathological structure (PrP Sc ) [1]. CWD is most prevalent in North America with reported cases in 25 US states and four Cana- dian provinces, and additional cases in South Korea, Norway, and Finland [2]. The disease has a significant impact in both captive and free-ranging cervids resulting in economic losses, declining populations, and public concern [3–5]. Currently, there is no effective vaccine or treatment for CWD. While some research suggests that harvest and/or culling strategies could be used to suppress the disease in free-ranging populations [6–8], the long incubation period and environmental persistence of CWD prions present significant management https://doi.org/10.1016/j.vaccine.2018.10.057 0264-410X/Published by Elsevier Ltd. ⇑ Corresponding author at: Wyoming Game and Fish Department, 1212 South Adams St, Laramie, WY, USA. E-mail address: mary.wood@wyo.gov (M.E. Wood). Vaccine xxx (2018) xxx–xxx Contents lists available at ScienceDirect Vaccine journal homepage: www.elsevier.com/locate/vaccine Please cite this article in press as: Wood ME et al. Accelerated onset of chronic wasting disease in elk (Cervus canadensis) vaccinated with a PrP Sc -specific vaccine and housed in a prion contaminated environment. Vaccine (2018), https://doi.org/10.1016/j.vaccine.2018.10.057