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
prions.
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.