Abstract
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.
Highlights
Prion diseases, or transmissible spongiform encephalopathies (TSE), are infectious neurodegenerative conditions that typically lead to cognitive and motor dysfunction [1,2]
Variant CreutzfeldtJakob disease is believed to be caused by the consumption of beef contaminated with bovine spongiform encephalopathy (BSE) prions, as strongly suggested by epidemiological, biochemical and neuropathological analyses as well as transmission studies [9,10,11,12,13,14,15]
For the following two weeks, treatment was suspended in order to prevent damage to secondary lymphoid organs as observed following longterm administration of CpG-ODN
Summary
Transmissible spongiform encephalopathies (TSE), are infectious neurodegenerative conditions that typically lead to cognitive and motor dysfunction [1,2]. Variant CreutzfeldtJakob disease (vCJD) is believed to be caused by the consumption of beef contaminated with BSE prions, as strongly suggested by epidemiological, biochemical and neuropathological analyses as well as transmission studies [9,10,11,12,13,14,15]. The association between BSE and vCJD, together with the high number (at least 190,000) of BSE infected cows, mainly in the UK in the 1980s and early 1990s, suggest a highly prevalent exposure of the European population to BSE prions and have raised fears of an upcoming vCJD epidemic. The incidence of vCJD remained disproportionally low: roughly 200 human individuals succumbed to vCJD until now and the incidence is declining
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