MedicalResearch.com Interview with:
Thomas Wisniewski MD
Lulu P. and David J. Levidow Professor of Neurology
Professor; Director Aging and Dementia
New York University School of Medicine
Dept. of Neurology, Psychiatry and Pathology
New York, NY 10016
Medical Research: What is the background for this study? What are the main findings?
Dr. Wisniewski: Chronic wasting disease (CWD) infects large numbers of deer and elk, with the potential to infect humans. Currently no prionosis has an effective treatment. This is a relatively new prion disease that has many similarities to bovine spongiform encephalopathy which spread to humans to produce new variant Creutzfeldt-Jakob disease. Chronic wasting disease is the most infectious prion disease to date; having the potential to spread by aerosol. Previously, we have demonstrated we could prevent transmission of prions in a proportion of susceptible mice with a mucosal vaccine. In the current study, white-tailed deer were orally inoculated with attenuated Salmonella expressing PrP, while control deer were orally inoculated with vehicle attenuated Salmonella. Once a mucosal response was established, the vaccinated animals were boosted orally and locally by application of polymerized recombinant PrP onto the tonsils and rectal mucosa. The vaccinated and control animals were then challenged orally with CWD-infected brain homogenate. Three years post CWD oral challenge all control deer developed clinical CWD (median survival 602 days), while among the vaccinated there was a significant prolongation of the incubation period (median survival 909 days; p=0.012 by Weibull regression analysis) and one deer has remained CWD free both clinically and by RAMALT and tonsil biopsies. This negative vaccinate has the highest titers of IgA in saliva and systemic IgG against PrP. Western blots showed that immunoglobulins from this vaccinate react to PrPCWD. We document the first partially successful vaccination for a prion disease in a species naturally at risk.
Medical Research: What should clinicians and patients take away from your report?
Dr. Wisniewski: Prion disease is a unique category of illness, affecting both animals and humans, in which the underlying pathogenesis is related to a conformational change of a normal, self-protein called PrPC (C for cellular) to a pathological and infectious conformer known as PrPSc (Sc for scrapie). They are dramatic and tragic illnesses, which are universally fatal. Creutzfeldt-Jakob disease is the most common human prionosis; from onset to death the course is typically ~ 7 months. We report the first partially successful vaccine for a prion disease in a species naturally at risk for prion disease. This suggests that a vaccine for other types of prion disease might also be possible.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Wisniewski: We plan to improve the formatulation of our vaccine and re-test, with the hope and expectation that we will be able to acheive a greater level of protection. We plan to also test this vaccine for human prion diseases.
Mucosal immunization with an attenuated Salmonella vaccine partially protects white-tailed deer from chronic wasting disease
Fernando Goñi, Candace K. Mathiason, Lucia Yim, Kinlung Wong, Jeanette Hayes-Klug, Amy Nalls, Daniel Peyser, Veronica Estevez, Nathaniel Denkers, Jinfeng Xu, David A. Osborn, Karl V. Miller, Robert J. Warren,David R. Brown, Jose A. Chabalgoityf,Edward A. Hoovere, Thomas Wisniewskia