PrPSc binding antibodies are potent inhibitors of prion replication in cell lines.
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.
Beringue
Vincent
V
Department of Neurogenetics, CNS Infection and Immunity Group, Faculty of Medicine, Imperial College, London W2 1PG, United Kingdom.
Vilette
Didier
D
Mallinson
Gary
G
Archer
Fabienne
F
Kaisar
Maria
M
Tayebi
Mourad
M
Jackson
Graham S
GS
Clarke
Anthony R
AR
Laude
Hubert
H
Collinge
John
J
Hawke
Simon
S
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
D000911:Antibodies, Monoclonal; D018621:PrPC Proteins; D018620:PrPSc Proteins