NR AXIK
AU Azadeh,K.S.; Carswell,C.; Quaratino,S.; Martins,S.; Properzi,F.; Mushens,R.; Clarke,A.R.; Jackson,G.S.; Anstee,D.; Collinge,J.
TI Immunotherapy- Active and Passive Immunisations in Prion Disease
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.155
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
Background: The observation that vCJD is transmissible by blood transfusion has highlighted the need to find a treatment for prion diseases. Although no immune response is observed in prion disease due to tolerance of nascent PrPc, active immunisation in some models has provided partial protection. We have already produced monoclonal antibodies (mAb) ICSM18 (IgG1 to epitope 142-153) and ICSM35 (IgG2b to epitope 93-105) to recombinant (r) human a- and ß-PrP, and their passive transfer offered a significant protection against prion disease in mice.
Aims: (1) To optimise IgG dose for passive transfer and investigate side-effects of continuous mAb therapy. (2) To study responses and efficacy by active immunisation of different mouse strains.
Methods: (1) RML prion-infected and uninfected mice were treated biweekly with various IgG doses and the integrity of antigen presenting cells (APC), T and B cells are examined. (2) The immune responses, longevity, brain and splenic infectivity and PrPsc levels are investigated in actively immunised and RML prion-infected mice.
Results: (1) ICSM18 at 1mg/ml but not 0.1 mg/ml was effective in controlling splenic PrPsc levels. Further evaluation of long-term effects, especially the integrity of T cells, B cells and APC are underway. (2) Active immunisation of SJL and FVB/N mice led to PrP-specific T cell and Ab responses. The Abs cross-react between r human and mouse PrP, a- and ß-PrP and recognise native PrP. An existing prion infection did not affect Ab production and titres were maintained until end-point. At post infection day (PID) 57-75 splenic PrPsc decreased in r PrP immunised FVB/N and SJL mice.
Conclusion: (1) Passive immunisation remains a realistic therapy for prion disease, particularly after optimising the dose and timing of mAb therapy, and investigating possible side-effects. Studies are underway to determine the potential use of Ab fragments and translocation across the blood brain barrier. (2) Although r PrPimmunised SJL mice survived longer than untreated mice, PrPsc levels and infectivity
eventually increased leading to disease. These promising results suggest that active immunisation has potential as a therapeutic strategy.
AD K.S. Azadeh, C. Carswell, S. Martins, F. Properzi, A. Clarke, G. Jackson, J. Collinge, Institute of Neurology, UCL, Dep of Neurodegenerative Disease & MRC Prion Unit, UK; S. Quaratino, School of Medicine, University of Southampton, Cancer Research UK Clinical Centre, UK; R. Mushens, D. Anstee, International Blood Group Reference Laboratory, UK
SP englisch
PO Schottland