Induction of antibodies against murine full-length prion protein in wild-type mice.
The causative and infectious agent of the transmissible spongiform encephalopathies, e.g. bovine spongiform encephalopathy in cattle or variant Creutzfeldt-Jakob disease in humans, is a pathogenic form of the scrapie prion protein (PrP(Sc)) generated by a conformational rearrangement in the normal cellular prion protein (PrP(C)). Anti-PrP antibodies have been shown to exert a protective effect against infection with PrP(Sc). However, the generation of anti-PrP antibodies has proven quite difficult in wild-type animals, PrP being a notoriously poor immunogen. We developed a vaccine against PrP by mixing recombinant murine PrP 23-231 with DnaK, an Hsp70 homolog in Escherichia coli, and cross-linking the two proteins by means of glutaraldehyde. After three injections of the vaccine into BALB/c mice at 6, 8 and 9 weeks of age, a low-titer immune response was detected with ELISA in all animals. The specificity of the antibodies for PrP was confirmed with Western blotting. The straightforward procedure might render active immunization against prion infection feasible.
Koller
Michael F
MF
Biochemisches Institut, Universität Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
Grau
Thomas
T
Christen
Philipp
P
D000818:Animals; D000906:Antibodies / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D029968:Escherichia coli Proteins; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D011328:Prions / Q000276:immunology*; D014612:Vaccines / Q000276:immunology
D000906:Antibodies; D029968:Escherichia coli Proteins; D018840:HSP70 Heat-Shock Proteins; D011328:Prions; D014612:Vaccines; C063842:dnaK protein, E coli