PrP^Sc binding antibodies are potent inhibitors of prion replication in cell lines

Conversion of the cellular α-helical prion protein (PrP^C) into a disease-associated isoform (PrP^Sc) is central to the pathogenesis of prion diseases. Molecules targeting either normal or disease-associated isoforms may be of therapeutic interest, and the antibodies binding PrP^C have been shown to inhibit prion accumulation in vitro. Here we investigate whether antibodies that additionally target disease-associated isoforms such as PrP^Sc inhibit prion replication in ovine PrP-inducible scrapie-infected Rov cells. We conclude from these experiments that antibodies exclusively binding PrP^C were relatively inefficient inhibitors of ScRov cell PrP^Sc accumulation compared with antibodies that additionally targeted disease-associated PrP isoforms. Although the mechanism by which these monoclonal antibodies inhibit prion replication is unclear, some of the data suggest that antibodies might actively increase PrP^Sc turnover. Thus antibodies that bind to both normal and disease-associated isoforms represent very promising anti-prion agents.