Mucosal vaccination delays or prevents prion infection via an oral route

• Published in: Neuroscience Vol. 133; no. 2; pp. 413 - 421
• Main Authors: Goñi, F., Knudsen, E., Schreiber, F., Scholtzova, H., Pankiewicz, J., Carp, R., Meeker, H.C., Rubenstein, R., Brown, D.R., Sy, M.-S., Chabalgoity, J.A., Sigurdsson, E.M., Wisniewski, T.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 2005; Elsevier
• Subjects: Administration, Oral; Alzheimer’s disease; amyloid β; Analysis of Variance; Animals; Biological and medical sciences; Blotting, Western - methods; bovine spongiform encephalopathy; BSE; chronic wasting disease; Creutzfeldt-Jakob disease; CWD; ELISA; enzyme-linked immunosorbent assay; Female; fragment C of tetanus toxin; Fundamental and applied biological sciences. Psychology; gastro-intestinal; Gene Expression Regulation, Viral - physiology; Human viral diseases; immunization; immunoglobulin; Immunoglobulin A - metabolism; Immunoglobulin G - metabolism; Immunotherapy; Infectious diseases; lipopolysaccharide; LPS; Medical sciences; Mice; Mucous Membrane - immunology; PBST; phosphate-buffered saline, 0.1% Tween-20; Prion Diseases - immunology; Prion Diseases - prevention & control; Prion Diseases - virology; prion protein cellular; prion protein scrapie; Protein Conformation; PrP C; PrP Sc; PrPC Proteins - chemistry; PrPC Proteins - immunology; recombinant prion protein; recPrP; Salmonella; Salmonella vaccine strain; scrapie; TetC; Time Factors; Vaccination; variant Creutzfeldt-Jakob disease; vCJD; Vertebrates: nervous system and sense organs; Viral diseases; Viral diseases of the nervous system; GI; AD; bovine spongiform encephalopathy; Creutzfeldt-Jakob disease; TetC; chronic wasting disease; PrP C; PrP Sc; Salmonella vaccine strain; LPS; Aβ; CWD; vCJD; BSE; immunization; PBST; recPrP; scrapie; Ig; ELISA; Scrapie; Vaccination; Ox; Prevention; Degenerative disease; Spongiform encephalopathy; Ungulata; Prion disease; Nervous system diseases; Bovine; Oral administration; Cerebral disorder; Infection; Vertebrata; Chronic; Mammalia; Animal; Central nervous system disease; Sheep; Prion; Artiodactyla; Creutzfeldt Jakob disease
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2005.02.031

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.