Single chain Fv antibodies directed against the 37Â kDa/67Â kDa laminin receptor as therapeutic tools in prion diseases

Transmissible spongiform encephalopathies are a group of neurological disorders associated with the deposition of PrPSc, an abnormal form of the cellular prion protein PrPc. The 37 kDa/67 kDa laminin receptor (LRP/LR) has been identified as a prion receptor and several lines of evidence strongly suggest that this protein plays a role during prion pathogenesis. Here we report the selection of recombinant single chain antibodies (scFvs) directed against LRP from naïve and synthetic phage scFv libraries for therapeutic application. Western blotting and FACS analysis confirmed a specific LRP/LR recognition pattern of the two selected scFvs S18 and N3. Both scFvs specifically interfered with the PrP/LRP interaction in vitro. High yield production of the scFvs of approx. 1 mg/l of culture medium was achieved in E. coli. Passive immunotransfer of the scFv S18 antibody reduced PrPSc levels by approx. 40% in the spleen of scrapie infected C57BL/6 mice 90 days post scFv injection, suggesting that scFv S18 interferes with peripheral PrPSc propagation, without a significant prolongation of incubation and survival times.