552. Single-Chain Antibodies for Viral-Based Passive Immuno-Therapy for Prion Disease: Linear Epitope Mapping and Clearance from Thalamic Injection

Transmissible spongiform encephalopathies (TSE) are characterized by the conversion of a normal cellular protein (PrPc) to an abnormal disease causing conformation, designated PrPsc. Efforts to use antibodies to alter the rate of conversion of PrPc to PrPsc suggest it to be a plausible therapeutic strategy. Notably, during the normal progression of disease the host organism mounts no detectable immune response to alter the process of PrPsc accumulation. This is hypothesized to be due to the low antigenicity of PrPc and host tolerance to a self-polypeptide. We intend to circumvent the lack of a host-based immune response to impede the conversion of PrPc using novel PrPc-specific single-chain variable fragment (scFv) antibodies that will be utilized in a viral-based passive immuno-therapy. Several PrPc-specific antibodies have been obtained from a naïve human combinatorial phage display library. Epitope mapping has been performed on our scFvs using an ELISA based peptide array for linear epitope determination. We have also investigated the clearance of scFvs from a thalamic injection and determined the elimination half-life (T 1/2 ).