Development of an oral vaccine for chronic wasting disease
Posted Aug 11 2013 12:15pm
AD.24: Development of an oral vaccine for chronic wasting disease
Ryan Taschuk1,3 Kristen Marciniuk,1,2 Suresh Tikoo,1,3 Philip Griebel,1 Andrew Potter,1 Neil Cashman5 and Scott Napper1,2
1University of Saskatchewan; VIDO-lnterVac; Saskatoon, SK Canada; 2Department of Biochemistry; University of Saskatchewan; Saskatoon, SK Canada; 3School of Public Health; University of Saskatchewan; Saskatoon, SK Canada; 4Brain Research Centre; University of British Columbia; Vancouver, BC Canada; 5Brain Research Center; University of British Columbia; Vancouver, BC Canada
The prion protein is well conserved across mammals, and the misfolded protein is the causative agent in many animal-specific prion diseases, including chronic wasting disease (CWD) in deer and elk. Prion diseases are caused by misfolding of endogenously expressed prion protein from the native and homeostatic Prpc conformation to the infectious and pathogenic PrPsc conformation. Transmissible spongiform encephalopathies are of great interest for many reasons: the onset of disease inevitably leads to neurodegeneration and death, the potential of interference with food production through transmission both within and between agricultural species can have severe economic impacts, and the potential exists for zoonotic transmission. Our group has hypothesized that immunotherapeutic targeting of the PrPSc conformation would clear the infectious agent / infected cell while sparing native PrP, and vaccines may have potential application in prevention of CWD transmission or therapeutic treatment of disease.
Our research has focused upon identifying and optimizing three components of a potential CWD vaccine: a CWD-disease specific epitope (DSE) that induces antibody responses, a carrier protein to increase the magnitude and duration of antibody responses toward DSEs, and identification of delivery systems for oral delivery of the above DSE-carrier protein ro cervids. We have developed and optimized DSEs from three distinct regions of PrPc. Vaccination trials using iterations of these DSEs elicit high titers of epitope-specific serum antibody. A second generation carrier protein has increased both the duration and magnitude of antibody responses when compared with our previous carrier protein. Lastly, two delivery systems were effective in inducing antibody responses when administered orally to white-tailed deer. We have identified the vaccine components necessary for delivering a CWD vaccine to wild cervids. These findings will direct our final CWD vaccine formulation and delivery system.