NR AXLP
AU Eloit,M.; Sacquin,A.; Adam,M.; Crespeau,F.; Rosset,M.
TI Adenovirus-mediated Vaccination Induces Antibody and T CD8+ Responses to PrP in Wild-type Mice: Role in Protection of Prion Disease
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.186
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
Background: Anti-PrP antibodies (Abs) are able to inhibit PrPc to PrPsc conversion in vitro and prion pathogenesis in vivo. Other effectors with potential to clear PrPsc producing cells are Cytotoxic T Lymphocytes (CTL) directed against PrP-derived peptides, but it is currently unknown whether they can confer protection. Yet, as the PrP is a self-Ag, the major problem is the immune tolerance which must be bypassed at risk of autoimmune manifestations.
Aim(s)/Objective(s): To induce in C57BL/6 wt mice an humoral or CTL responses directed to PrP by using recombinant adenovirus vectors encoding entire or fragments of PrP gene expressing CD8 T-cell or B-cell epitopes and assess their efficiency against challenge.
Methods: Different rAd constructs expressing xenogenic PrP or minigenes encoding peptides with high affinity for MHCI, together with different schemes of immunization were tested in wild-type mice to induce anti-PrP immune responses in wild-type mice: parenteral injection of the rAds, ex vivo transduction of dendritic cells by rAds and elimination of CD4+CD25+ regulatory T cells before immunization.
Results: We will present results from a series of vaccination experiments in C57BL/6 mice with the different rAd constructs. Specificity and intensity of antibody responses in immunized mice were analysed by ELISA and cytofluorimetric methods using cells expressing different PrP species. We were able to induce antibodies against the native murine PrP and/or peptide-specific T CD8+ cells cytotoxic in vitro and in vivo, without deleterious autoimmune reactions. Protection studies are currently ongoing in mice infected with 139A scrapie.
Conclusion: This strategy proves particularly efficient to elicit cross reactive antibodies and CTL against murine PrP, whose protective capacity is under investigation in prion infected mice.
AD M. Eloit, M. Adam, ENVA, UMR 1161, France; A. Sacquin, M. Rosset, INSERM, 712/Hopital St Antoine, France; F. Crespeau, ENVA, UP d'Antomie Pathologie, France
SP englisch
PO Schottland