966. AAV Delivered Single-Chain Antibodies as Passive Immuno-Therapy for Prion Disease

Abstract

Top of pageAbstract 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 and previously characterized PrPc-specific single-chain variable fragment (scFv) antibodies that will be utilized in an AAV-based passive immuno-therapy. Several novel PrPc-specific antibodies have been obtained from a na|[iuml]|ve human combinatorial phage display library. Antibody D18 has been previously characterized with the ability to clear PrPsc from chronically infected cell-lines. Gross motor coordination of immunized challenged mice is being monitored by Rotarod performance. Data from ongoing evaluation of these vaccinated animals will be presented.