title: Intranasal immunization of Balb/c mice against prion protein attenuates orally acquired transmissible spongiform encephalopathy.
abstract: To test whether prion protein (PrP) specific secretory immunoglobulin A (sIgA) can be induced and protect against oral transmission of spongiform encephalopathy (SE) we immunized Balb/c mice either intragastrically or intranasally (i.n.) with a recombinant PrP-fragment (PrP90-231) and cholera toxin (CT) adjuvant. Since PrP90-231 was rapidly digested in intestinal lavage, aprotinin was added to some vaccine formulations. While an anti-CT response was elicited via both routes, solely i.n. immunization without aprotinin induced PrP-specific sIgA. They recognize predominantly PrP-oligomers as the antigen was aggregated in the vaccine formulations. Challenge experiments showed that the immune response induced by our protocol could not prevent disease, but increases the median survival of the animals. We conclude that PrP-specific sIgA reduce the infectivity of the inoculum and that complete protection against transmission of SE should be achievable by optimized immunization regimens.
authors.affiliation: Research Center Borstel, Parkallee 22, D-23845 Borstel, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Bade
authors.forename: Michael
authors.initials: M
authors.lastname: Baier
authors.forename: Thurid
authors.initials: T
authors.lastname: Boetel
authors.forename: Andreas
authors.initials: A
authors.lastname: Frey
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology; D000281:Administration, Intranasal; D000818:Animals; D007611:Aprotinin / Q000008:administration & dosage / Q000494:pharmacology; D002772:Cholera Toxin / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D005243:Feces; D005260:Female; D018928:Immunity, Mucosal; D007071:Immunoglobulin A, Secretory / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000276:immunology; D017096:Prion Diseases / Q000276:immunology / Q000517:prevention & control* / Q000635:transmission; D011328:Prions / Q000008:administration & dosage* / Q000276:immunology; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D014556:Urine; D014614:Vaccines, Synthetic / Q000008:administration & dosage* / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D010446:Peptide Fragments; D011328:Prions; D015842:Serine Proteinase Inhibitors; D014614:Vaccines, Synthetic; D002772:Cholera Toxin; D007611:Aprotinin