title: Mucosal immunization with an attenuated Salmonella vaccine partially protects white-tailed deer from chronic wasting disease.
abstract: 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 PrP(C) (C for cellular) to a pathological and infectious conformer known as PrP(Sc) (Sc for scrapie). Bovine spongiform encephalopathy (BSE), a prion disease believed to have arisen from feeding cattle with prion contaminated meat and bone meal products, crossed the species barrier to infect humans. Chronic wasting disease (CWD) infects large numbers of deer and elk, with the potential to infect humans. Currently no prionosis has an effective treatment. 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 PrP(CWD). We document the first partially successful vaccination for a prion disease in a species naturally at risk.
authors.affiliation: Department of Neurology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, United States.
authors.forename: Fernando
authors.initials: F
authors.lastname: Goñi
authors.affiliation: College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States.
authors.forename: Candace K
authors.initials: CK
authors.lastname: Mathiason
authors.affiliation: Laboratory for Vaccine Research, Department of Biotechnology, Instituto de Higiene, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
authors.forename: Lucia
authors.initials: L
authors.lastname: Yim
authors.affiliation: Department of Neurology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, United States.
authors.forename: Kinlung
authors.initials: K
authors.lastname: Wong
authors.affiliation: College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States.
authors.forename: Jeanette
authors.initials: J
authors.lastname: Hayes-Klug
authors.affiliation: College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States.
authors.forename: Amy
authors.initials: A
authors.lastname: Nalls
authors.affiliation: Department of Neurology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Peyser
authors.affiliation: Laboratory for Vaccine Research, Department of Biotechnology, Instituto de Higiene, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
authors.forename: Veronica
authors.initials: V
authors.lastname: Estevez
authors.affiliation: College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Denkers
authors.affiliation: Department of Population Health, New York University School of Medicine, 550 First Avenue, New York, NY 10016, United States.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Xu
authors.affiliation: Warnell School of Forestry and Natural Resources, University of Georgia, United States.
authors.forename: David A
authors.initials: DA
authors.lastname: Osborn
authors.affiliation: Warnell School of Forestry and Natural Resources, University of Georgia, United States.
authors.forename: Karl V
authors.initials: KV
authors.lastname: Miller
authors.affiliation: Warnell School of Forestry and Natural Resources, University of Georgia, United States.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Warren
authors.affiliation: Department of Biology and Biochemistry, University of Bath, UK.
authors.forename: David R
authors.initials: DR
authors.lastname: Brown
authors.affiliation: Laboratory for Vaccine Research, Department of Biotechnology, Instituto de Higiene, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Chabalgoity
authors.affiliation: College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Hoover
authors.affiliation: Department of Neurology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, United States; Department of Pathology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, United States; Department of Psychiatry, New York University School of Medicine, 550 First Avenue, New York, NY 10016, United States. Electronic address: thomas.wisniewski@nyumc.org.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wisniewski
mesh_terms: D058956:Administration, Mucosal; D000818:Animals; D001769:Blood / Q000276:immunology; D003670:Deer; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000097:blood; D011328:Prions / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D012463:Saliva / Q000276:immunology; D022562:Salmonella Vaccines / Q000008:administration & dosage* / Q000235:genetics; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D034081:Wasting Disease, Chronic / Q000276:immunology / Q000517:prevention & control*
chemical_list: D007070:Immunoglobulin A; D007074:Immunoglobulin G; D011328:Prions; D022562:Salmonella Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic
keywords: Bovine spongiform encephalopathy; Chronic wasting disease; Immunization; Mucosal vaccination; Prion protein; Salmonella vaccine strain; White-tailed deer