Unswitched immunoglobulin M response prolongs mouse survival in prion disease.
Several studies have failed to demonstrate the presence of immune responses to infectious prions during the course of prion disease, reflecting the identical primary structure of normal and disease-associated isoforms and the widespread expression of the normal cellular form of prion protein, PrP(C), leading to B- and/or T-cell tolerance of disease-associated isoforms and also possibly because antigen-presenting cells are unable to process the highly aggregated, detergent-insoluble, protease-resistant form, PrP(Sc). Under certain circumstances, PrP(Sc) can be revealed to the immune system in immunogenic form, and it has been shown previously that anti-PrP antibodies can be induced to prions immunoadsorbed to Dynabeads using specific anti-PrP monoclonal antibodies, even in PrP-sufficient mice. This study demonstrated in a murine scrapie model that PrP-Dynabeads effectively stimulated the immune system to produce anti-PrP IgM antibodies over prolonged periods after repeated immunization. It was also shown that these immune responses prolonged incubation times in murine scrapie.
Tayebi
Mourad
M
Brain & Mind Research Institute, University of Sydney, 100 Mallett Street, Camperdown, NSW 2050, Australia.|Department of Pathology and Infectious Diseases, Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Hertfordshire AL9 7TA, UK.
Collinge
John
J
MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
Hawke
Simon
S
Brain & Mind Research Institute, University of Sydney, 100 Mallett Street, Camperdown, NSW 2050, Australia.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology; D005260:Female; D007114:Immunization; D007075:Immunoglobulin M / Q000097:blood*; D018189:Immunomagnetic Separation / Q000379:methods*; D051379:Mice; D018620:PrPSc Proteins / Q000737:chemistry / Q000276:immunology; D017096:Prion Diseases / Q000276:immunology* / Q000378:metabolism / Q000401:mortality*; D012608:Scrapie / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D007075:Immunoglobulin M; D018620:PrPSc Proteins