Immunisation with a synthetic prion protein-derived peptide prolongs survival times of mice orally exposed to the scrapie agent

Schwarz, Anja; Krätke, Oliver; Burwinkel, Michael; Riemer, Constanze; Schultz, Julia; Henklein, Peter; Bamme, Theresa; Baier, Michael

doi:10.1016/s0304-3940(03)00907-8

Cited by 85 publications

(67 citation statements)

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“…However, no effect on disease development was observed after immunization with PrP90 -230 while treatment with P105-125 prolonged the incubation period by an average of 23 days (12). Interestingly, Ab reactivities after PrP90 -230 immunization were predominantly directed to PrP fragment spanning from residues 159 to 211, and Abs against regions 105-125 and 144 -152 were undetectable (12). This pointed out the importance of the PrPc region bound by a given Ab for its inhibitory capacity in PrPSc replication.…”

Section: Discussionmentioning

confidence: 93%

“…Other T and B cell epitopes may exist on other PrP regions than those targeted by the four tested peptides. Many studies were recently dedicated to the development of strategies to trigger an anti-PrP immune response: Ab responses with variable titers were obtained after immunization with peptide conjugated with keyhole limpet hemocyanin (12) or emulsified in CFA (9, 16), recombinant full-length (10), truncated (12), or dimeric PrP (11) in CFA. Some of these treatments (10,12) resulted in a prolongation of survival of mice inoculated with a scrapie strain.…”

Section: Discussionmentioning

confidence: 99%

“…Many studies were recently dedicated to the development of strategies to trigger an anti-PrP immune response: Ab responses with variable titers were obtained after immunization with peptide conjugated with keyhole limpet hemocyanin (12) or emulsified in CFA (9, 16), recombinant full-length (10), truncated (12), or dimeric PrP (11) in CFA. Some of these treatments (10,12) resulted in a prolongation of survival of mice inoculated with a scrapie strain. However, no effect on disease development was observed after immunization with PrP90 -230 while treatment with P105-125 prolonged the incubation period by an average of 23 days (12).…”

Section: Discussionmentioning

confidence: 99%

“…Some of these treatments (10,12) resulted in a prolongation of survival of mice inoculated with a scrapie strain. However, no effect on disease development was observed after immunization with PrP90 -230 while treatment with P105-125 prolonged the incubation period by an average of 23 days (12). Interestingly, Ab reactivities after PrP90 -230 immunization were predominantly directed to PrP fragment spanning from residues 159 to 211, and Abs against regions 105-125 and 144 -152 were undetectable (12).…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies reported that humoral response against PrP can be induced not only in PrP knockout (Prnp Ϫ/Ϫ ) mice (5,6,7) or in xenogenic systems (8), but also in wild-type (PrP ϩ ) mice when tolerance to PrP was overcome by strong immunization procedures (9,10,11,12). Moreover, protective immunity against scrapie agent propagation was obtained with antiPrP Abs when induced by active immunization (10,12) or injected passively (13). Similarly, in a mouse model of Alzheimer's disease, immunization with fibrillar A␤1-42-induced Abs that impaired the accumulation of amyloid plaques in the brain of mice and prevented the onset of neurological disease (14).…”

mentioning

confidence: 99%

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

Rosset

Ballerini

Grégoire

et al. 2004

The Journal of Immunology

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The absence of a detectable immune response during transmissible spongiform encephalopathies is likely due to the fact that the essential component of infectious agents, the prion protein (PrP), is a self Ag expressed on the surface of many cells of the host. To overcome self-tolerance to PrP, we used 30-mer PrP peptides previously shown to be immunogenic in Prnp−/− mice, together with CFA or CpG-oligodeoxynucleotides (CpG) in IFA. Generation of anti-PrP T and B cell responses was analyzed in the spleen, lymph nodes, and serum of immunized C57BL/6 wild-type mice. Immunization with PrP peptides emulsified in CFA did not trigger an immune response to PrP. When CpG were used, vaccination with peptides P143–172 and P158–187 generated IFN-γ-secreting splenic T cells, and only P158–187 significantly stimulated IL-4-secreting T cells. Both peptides induced few Ab-producing B cells, and low and variable serum Ab titers. In contrast, immunization with peptide P98–127 did not induce significant levels of T cell responses but elicited specific peptide Abs. T cell epitope mapping, performed using 15-mer peptides covering PrP segment 142–182, revealed that an immunogenic motif lies between positions 156 and 172. These results demonstrate that T and B cell repertoires against PrP can be stimulated in C57BL/6 when adjuvant of the innate immunity such as CpG, but not CFA, is added to PrP peptides, and that the pattern of immune responses varies according to the epitope.

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Section: Discussionmentioning

confidence: 93%