title: PrPSc binding antibodies are potent inhibitors of prion replication in cell lines.
abstract: Conversion of the cellular alpha-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.
authors.affiliation: Department of Neurogenetics, CNS Infection and Immunity Group, Faculty of Medicine, Imperial College, London W2 1PG, United Kingdom.
authors.forename: Vincent
authors.initials: V
authors.lastname: Beringue
authors.forename: Didier
authors.initials: D
authors.lastname: Vilette
authors.forename: Gary
authors.initials: G
authors.lastname: Mallinson
authors.forename: Fabienne
authors.initials: F
authors.lastname: Archer
authors.forename: Maria
authors.initials: M
authors.lastname: Kaisar
authors.forename: Mourad
authors.initials: M
authors.lastname: Tayebi
authors.forename: Graham S
authors.initials: GS
authors.lastname: Jackson
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Clarke
authors.forename: Hubert
authors.initials: H
authors.lastname: Laude
authors.forename: John
authors.initials: J
authors.lastname: Collinge
authors.forename: Simon
authors.initials: S
authors.lastname: Hawke
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology*; D000918:Antibody Specificity; D002460:Cell Line; D051379:Mice; D008817:Mice, Mutant Strains; D018621:PrPC Proteins / Q000235:genetics; D018620:PrPSc Proteins / Q000276:immunology* / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D018621:PrPC Proteins; D018620:PrPSc Proteins