Complete Freund's adjuvant immunization prolongs survival in experimental prion disease in mice

Abstract

We recently reported that immunization of mice with certain self-prion protein peptides induced specific T-cell and B-cell immune responses; importantly, this immunization was associated with a decrease in the number of protease-resistant PrP(Sc) particles recoverable in a transplanted, scrapie-infected syngeneic tumor. The present study was carried out to determine whether immunization with the immunogenic PrP peptides might influence the natural history of experimental scrapie in mice. We immunized C57BL/6 mice with self-prion peptides in complete Freund's adjuvant (CFA) or with CFA alone as a control and then infected the mice with mouse-adapted scrapie by injection either intraperitoneally or intracerebrally. We report here that immunization with CFA, irrespective of whether prion peptides were present in the inoculum, resulted in marked prolongation of survival of the mice, whether the challenge was intracerebral or intraperitoneal. Mice in the immunized and control groups that died contained equivalent amounts of PrP(Sc). Thus, CFA immunization has a therapeutic effect in experimental scrapie in mice, possibly by reducing the rate of PrP(Sc) accumulation in the brain.

Unswitched immunoglobulin M response prolongs mouse survival in prion disease

“…These results are not in agreement with the findings of Tal et al (2003), who demonstrated an increase in the incubation period and survival of scrapieinfected mice after injection with CFA, although equivalent amounts of PrP Sc were immunodetected in control and CFA-immunized mice.…”

Breaking Immune Tolerance to the Prion Protein Using Prion Protein Peptides Plus Oligodeoxynucleotide-CpG in Mice

“…A strong involvement of T cell or innate immunity might be required also for a prophylactic or therapeutic effect of immunization against PrP. Repeated injections of CpG (41) or CFA (42) without specific PrP Ag into mice delayed the onset of the clinical disease suggesting that effectors of innate immunity might protect against TSE development. However, a possible role of specific anti-PrP T cell responses were not explored in those studies; a strong T cell help may be necessary to enhance and sustain Ab production, but might also induce autoimmune side-effects.…”

Protective Role of Interferon Regulatory Factor 3-Mediated Signaling against Prion Infection

“…Since gliosis, a major characteristic of TSE, is thought to be a kind of inflammatory response, it is reasonable to assume that innate immunity may play a role in the pathogenesis of TSE. Indeed, it was reported that pretreatment with complete Freund's adjuvant (CFA) (39) or unmethylated CpG DNA (35), both of which activate innate immunity through TLRs, delays the onset of TSE in mice inoculated with mouse-adapted scrapie prion, suggesting that activation of innate immunity is protective against prion infection. In contrast, deletion of the MyD88 gene, which is an essential intracellular signal transducer in all TLRs except for TLR3, has been shown not to significantly affect incubation time in the same mouse scrapie model (29).…”