Intranasal immunization of Balb/c mice against prion protein attenuates orally acquired transmissible spongiform encephalopathy.
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.
Bade
Steffen
S
Research Center Borstel, Parkallee 22, D-23845 Borstel, Germany.
Baier
Michael
M
Boetel
Thurid
T
Frey
Andreas
A
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
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