PrP-specific camel antibodies with the ability to immunodetect intracellular prion protein.
Although there is currently no effective treatment for prion diseases, significant advances have been made in suppressing its progress, using antibodies that block the conversion of PrP(C) into PrP(Sc). In order to be effective in treating individuals that have prion diseases, antibodies must be capable of arresting disease in its late stages. This requires the development of antibodies with higher affinity for PrP(Sc) and systems for effective translocation of antibodies across the blood-brain barrier in order to achieve high concentrations of inhibitor at the site of protein replication. An additional advantage is the ability of these antibodies to access the cytosol of affected cells. To this end, we have generated PrP-specific antibodies (known as PrioV) by immunization of camels with murine scrapie material adsorbed to immunomagnetic beads. The PrioV antibodies display a range of specificities with some recognizing the PrP(27-30) proteinase K-resistant fragment, others specific for PrP(C) and a number with dual binding specificity. Independent of their PrP conformation specificity, one of the PrioV antibodies (PrioV3) was shown to bind PrP(C) in the cytosol of neuroblastoma cells. In marked contrast, conventional anti-PrP antibodies produced in mouse against similar target antigen were unable to cross the neuronal plasma membrane and instead formed a ring around the cells. The PrioV anti-PrP antibodies could prove to be a valuable tool for the neutralization/clearance of PrP(Sc) in intracellular compartments of affected neurons and could potentially have wider applicability for the treatment of so-called protein-misfolding diseases.
Tayebi
Mourad
M
Department of Pathology & Infectious Diseases, Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Hertfordshire AL9 7TA, UK.
Taylor
William Alexander
WA
Department of Pathology & Infectious Diseases, Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Hertfordshire AL9 7TA, UK.
Jones
Daryl Rhys
DR
Department of Pathology & Infectious Diseases, Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Hertfordshire AL9 7TA, UK.
Bate
Clive
C
Department of Pathology & Infectious Diseases, Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Hertfordshire AL9 7TA, UK.
David
Monique
M
Multiple Sclerosis Research Center of New York, Inc., 521 West 57th Street, 4th Floor, New York, NY 10019, USA.
D000818:Animals; D000906:Antibodies / Q000032:analysis* / Q000276:immunology*; D002162:Camelus; D003600:Cytosol / Q000737:chemistry; D051379:Mice; D009474:Neurons / Q000737:chemistry; D018620:PrPSc Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology* / Q000378:metabolism; D000072002:Prion Proteins; D011328:Prions / Q000276:immunology*
D000906:Antibodies; D018620:PrPSc Proteins; D000072002:Prion Proteins; D011328:Prions; C512657:Prnp protein, mouse