title: PrP(Sc)-specific antibodies with the ability to immunodetect prion oligomers.
abstract: The development of antibodies with binding capacity towards soluble oligomeric forms of PrPSc recognised in the aggregation process in early stage of the disease would be of paramount importance in diagnosing prion diseases before extensive neuropathology has ensued. As blood transfusion appears to be efficient in the transmission of the infectious prion agent, there is an urgent need to develop reagents that would specifically recognize oligomeric forms of the abnormally folded prion protein, PrPSc.To that end, we show that anti-PrP monoclonal antibodies (called PRIOC mAbs) derived from mice immunised with native PrP-coated microbeads are able to immunodetect oligomers/multimers of PrPSc. Oligomer-specific immunoreactivity displayed by these PRIOC mAbs was demonstrated as large aggregates of immunoreactive deposits in prion-permissive neuroblastoma cell lines but not in equivalent non-infected or prn-p(0/0) cell lines. In contrast, an anti-monomer PrP antibody displayed diffuse immunoreactivity restricted to the cell membrane. Furthermore, our PRIOC mAbs did not display any binding with monomeric recombinant and cellular prion proteins but strongly detected PrPSc oligomers as shown by a newly developed sensitive and specific ELISA. Finally, PrioC antibodies were also able to bind soluble oligomers formed of Aβ and α-synuclein. These findings demonstrate the potential use of anti-prion antibodies that bind PrPSc oligomers, recognised in early stage of the disease, for the diagnosis of prion diseases in blood and other body fluids.
authors.affiliation: Department of Pathology and Infectious Diseases, Royal Veterinary College, Hatfield, Hertfordshire, United Kingdom. mtayebi@rvc.ac.uk
authors.forename: Mourad
authors.initials: M
authors.lastname: Tayebi
authors.forename: Daryl Rhys
authors.initials: DR
authors.lastname: Jones
authors.forename: William Alexander
authors.initials: WA
authors.lastname: Taylor
authors.forename: Benjamin Frederick
authors.initials: BF
authors.lastname: Stileman
authors.forename: Charlotte
authors.initials: C
authors.lastname: Chapman
authors.forename: Deming
authors.initials: D
authors.lastname: Zhao
authors.forename: Monique
authors.initials: M
authors.lastname: David
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology*; D001704:Biopolymers / Q000032:analysis*; D002417:Cattle; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D006801:Humans; D051379:Mice; D018620:PrPSc Proteins / Q000737:chemistry / Q000276:immunology*; D012756:Sheep
chemical_list: D000906:Antibodies; D001704:Biopolymers; D018620:PrPSc Proteins