title: Mucosal vaccination delays or prevents prion infection via an oral route.
abstract: In recent years major outbreaks of prion disease linked to oral exposure of the prion agent have occurred in animal and human populations. These disorders are associated with a conformational change of a normal protein, PrP(C) (prion protein cellular), to a toxic and infectious form, PrP(Sc) (prion protein scrapie). None of the prionoses currently have an effective treatment. A limited number of active immunization approaches have been shown to slightly prolong the incubation period of prion infection. Active immunization in wild-type animals is hampered by auto-tolerance to PrP and potential toxicity. Here we report that mucosal vaccination with an attenuated Salmonella vaccine strain expressing the mouse PrP, is effective at overcoming tolerance to PrP and leads to a significant delay or prevention of prion disease in mice later exposed orally to the 139A scrapie strain. This mucosal vaccine induced gut anti-PrP immunoglobulin (Ig)A and systemic anti-PrP IgG. No toxicity was evident with this vaccination approach. This promising finding suggests that mucosal vaccination may be a useful method for overcoming tolerance to PrP and preventing prion infection among animal and potentially human populations at risk.
authors.affiliation: Department of Neurology, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: F
authors.initials: F
authors.lastname: Goñi
authors.forename: E
authors.initials: E
authors.lastname: Knudsen
authors.forename: F
authors.initials: F
authors.lastname: Schreiber
authors.forename: H
authors.initials: H
authors.lastname: Scholtzova
authors.forename: J
authors.initials: J
authors.lastname: Pankiewicz
authors.forename: R
authors.initials: R
authors.lastname: Carp
authors.forename: H C
authors.initials: HC
authors.lastname: Meeker
authors.forename: R
authors.initials: R
authors.lastname: Rubenstein
authors.forename: D R
authors.initials: DR
authors.lastname: Brown
authors.forename: M-S
authors.initials: MS
authors.lastname: Sy
authors.forename: J A
authors.initials: JA
authors.lastname: Chabalgoity
authors.forename: E M
authors.initials: EM
authors.lastname: Sigurdsson
authors.forename: T
authors.initials: T
authors.lastname: Wisniewski
mesh_terms: D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D007070:Immunoglobulin A / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D007167:Immunotherapy; D051379:Mice; D009092:Mucous Membrane / Q000276:immunology*; D018621:PrPC Proteins / Q000737:chemistry / Q000276:immunology*; D017096:Prion Diseases / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D011487:Protein Conformation; D013997:Time Factors; D014611:Vaccination
chemical_list: D007070:Immunoglobulin A; D007074:Immunoglobulin G; D018621:PrPC Proteins