Repetitive immunization enhances the susceptibility of mice to peripherally administered prions.
The susceptibility of humans and animals to prion infections is determined by the virulence of the infectious agent, by genetic modifiers, and by hitherto unknown host and environmental risk factors. While little is known about the latter two, the activation state of the immune system was surmised to influence prion susceptibility. Here we administered prions to mice that were repeatedly immunized by two initial injections of CpG oligodeoxynucleotides followed by repeated injections of bovine serum albumin/alum. Immunization greatly reduced the required dosage of peripherally administered prion inoculum necessary to induce scrapie in 50% of mice. No difference in susceptibility was observed following intracerebral prion challenge. Due to its profound impact onto scrapie susceptibility, the host immune status may determine disease penetrance after low-dose prion exposure, including those that may give rise to iatrogenic and variant Creutzfeldt-Jakob disease.
Institute of Neuropathology, Department of Pathology, University Hospital of Zurich, Zurich, Switzerland.
Juliane
J
Bremer
Mathias
M
Heikenwalder
Johannes
J
Haybaeck
Cinzia
C
Tiberi
Nike Julia
NJ
Krautler
Michael O
MO
Kurrer
Adriano
A
Aguzzi
D000818:Animals; D002417:Cattle; D018899:CpG Islands; D007562:Creutzfeldt-Jakob Syndrome / Q000517:prevention & control; D004198:Disease Susceptibility; D005260:Female; D007114:Immunization / Q000379:methods*; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D009841:Oligonucleotides / Q000737:chemistry; D011328:Prions / Q000378:metabolism*; D012307:Risk Factors; D012608:Scrapie / Q000517:prevention & control*; D012710:Serum Albumin, Bovine / Q000737:chemistry
D009841:Oligonucleotides; D011328:Prions; D012710:Serum Albumin, Bovine