Antibodies inhibit prion propagation and clear cell cultures of prion infectivity

David Peretz, R. Anthony Williamson (), Kiotoshi Kaneko, Julie Vergara, Estelle Leclerc, Gerold Schmitt-Ulms, Ingrid R. Mehlhorn, Giuseppe Legname, Mark R. Wormald, Pauline M. Rudd, Raymond A. Dwek, Dennis R. Burton and Stanley B. Prusiner
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David Peretz: Institute for Neurodegenerative Diseases, University of California,
R. Anthony Williamson: The Scripps Research Institute
Kiotoshi Kaneko: Institute for Neurodegenerative Diseases, University of California,
Julie Vergara: Institute for Neurodegenerative Diseases, University of California,
Estelle Leclerc: The Scripps Research Institute
Gerold Schmitt-Ulms: Institute for Neurodegenerative Diseases, University of California,
Ingrid R. Mehlhorn: Institute for Neurodegenerative Diseases, University of California,
Giuseppe Legname: Institute for Neurodegenerative Diseases, University of California,
Mark R. Wormald: The Glycobiology Institute, University of Oxford
Pauline M. Rudd: The Glycobiology Institute, University of Oxford
Raymond A. Dwek: The Glycobiology Institute, University of Oxford
Dennis R. Burton: The Scripps Research Institute
Stanley B. Prusiner: Institute for Neurodegenerative Diseases, University of California,

Nature, 2001, vol. 412, issue 6848, 739-743

Abstract: Abstract Prions are the transmissible pathogenic agents responsible for diseases such as scrapie and bovine spongiform encephalopathy. In the favoured model of prion replication, direct interaction between the pathogenic prion protein (PrPSc) template and endogenous cellular prion protein (PrPC) is proposed to drive the formation of nascent infectious prions1,2. Reagents specifically binding either prion-protein conformer may interrupt prion production by inhibiting this interaction. We examined the ability of several recombinant antibody antigen-binding fragments (Fabs) to inhibit prion propagation in cultured mouse neuroblastoma cells (ScN2a) infected with PrPSc. Here we show that antibodies binding cell-surface PrPC inhibit PrPSc formation in a dose-dependent manner. In cells treated with the most potent antibody, Fab D18, prion replication is abolished and pre-existing PrPSc is rapidly cleared, suggesting that this antibody may cure established infection. The potent activity of Fab D18 is associated with its ability to better recognize the total population of PrPC molecules on the cell surface, and with the location of its epitope on PrPC. Our observations support the use of antibodies in the prevention and treatment of prion diseases and identify a region of PrPC for drug targeting.

Date: 2001
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DOI: 10.1038/35089090

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