NR ATOL
AU Bade,S.; Baier,M.; Boetel,T.; Frey,A.
TI PrP-specific secretory immunoglobulin A induced by intranasal immunization of Balb/c mice decelerates progression of orally acquired spongiform encephalopathy
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Human prions, risk of blood products, and therapy HUMAN-35
PT Konferenz-Poster
AB
Transmissible spongiform encephalopathy (TSE) is assumed to spread by ingestion of prions, misfolded isoforms of the cellular prion protein (PrP). In the gastrointestinal tract, they either infect the epithelia directly or cross the epithelial layer and propagate systemically by catalyzing conversion of cellular PrP into new prions. As infections of this type are usually prevented by secretion of pathogen-specific immunoglobulin A (sIgA) onto the mucosal surfaces, prion-specific sIgA should be able to block the initiation of TSE.
To induce PrP-specific sIgA we immunized Balb/c mice either intragastrically (i.g.) or intranasally (i.n.) with a recombinant PrP-fragment (PrP90-231) and cholera toxin (CT) adjuvant. As in vitro digestion experiments showed a rapid degradation of PrP90-231 by intestinal fluid, we fortified some vaccine formulations by addition of the protease inhibitor aprotinin. While anti-CT sIgA was induced by both routes of immunization, neither vaccine formulation was able to provoke PrP-specific sIgA via the i.g. route. PrP-specific sIgA in feces and mucosal secretions was raised solely by i.n. immunization in the absence of aprotinin. The PrP-specific sIgA preferentially recognized PrP-oligomers, most likely because PrP90-231 was present in aggregated form in the vaccine formulation. To test the protective power of the PrP-specific sIgA we conducted oral challenge experiments with i.n. immunized Balb/c mice. The amount of PrP-specific sIgA induced was insufficient to protect the animals against infection, but it was able to decelerate progression of disease. This attenuation can be ascribed to a reduction of the infectious dose during oral inoculation. We therefore believe that a higher quantity of PrP-specific sIgA will be able to intercept ingested prions completely. If this assumption holds true mucosal vaccination against PrP will be a powerful tool to protect against orally acquired TSE.
AD S.Bade, T.Boetel, A.Frey, Research Center Borstel, Germany; M.Baier, Robert Koch-Institute, Germany
SP englisch
PO Deutschland