Decrease in pathology and progression of scrapie after immunisation with synthetic prion protein peptides in hamsters.
Effective therapy for prion diseases is currently unavailable. Recently, vaccination was shown to be effective in mouse models of a particular neurodegenerative conditions: Alzheimer's disease (AD). Here, we report that vaccination with synthetic oligopeptides homologous to the hamster (Mesocricetus auratus) prion protein augments survival time in animals infected intraperitoneally with 263K scrapie agent. For each hamster included in the study, prion-specific serum antibodies as well as deposition of pathological prion protein (PrP(res)), glial fibrillary acidic protein (GFAP), and mRNA expression for cytokines (TNF alpha, IL-1beta, IL-10) in brain tissues were evaluated. In immunized animals, increased survival after challenge was associated with a reduction of cerebral lesion, PrP deposition and GFAP expression; in these animals, anti-prion protein peptide antibody levels were increased, and the expression of pro-inflammatory cytokines (TNF alpha and IL-1beta) was reduced. Vaccination could be an effective therapeutic approach to postpone disease onset.
Magri
Giuliana
G
Laboratory of Immunology, DSP LITA Vialba, Universita' degli Studi di Milano, Via G.B. Grassi 74, 20157 Milano, Italy.
Clerici
Mario
M
Dall'Ara
Paola
P
Biasin
Mara
M
Caramelli
Maria
M
Casalone
Cristina
C
Giannino
Maria Laura
ML
Longhi
Renato
R
Piacentini
Luca
L
Della Bella
Silvia
S
Gazzuola
Paola
P
Martino
Piera Anna
PA
Della Bella
Silvia
S
Pollera
Claudia
C
Puricelli
Maria
M
Servida
Francesco
F
Crescio
Ines
I
Boasso
Adriano
A
Ponti
Wilma
W
Poli
Giorgio
G
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D006224:Cricetinae; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008647:Mesocricetus; D008969:Molecular Sequence Data; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry; D011328:Prions / Q000008:administration & dosage* / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D012608:Scrapie / Q000473:pathology* / Q000517:prevention & control; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D017931:DNA Primers; D007375:Interleukin-1; D010455:Peptides; D011328:Prions; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10