a camelid anti-prp antibody abrogates prpsc replication in prion-permissive neuroblastoma cell lines骆驼科anti-prp抗体废除prpsc复制在prion-permissive神经母细胞瘤细胞系.pdfVIP

A Camelid Anti-PrP Antibody Abrogates PrPSc Replication in Prion-Permissive Neuroblastoma Cell Lines 1 1 1 2 1 Daryl Rhys Jones , William Alexander Taylor , Clive Bate , Monique David , Mourad Tayebi * 1 Department of Pathology Infectious Diseases, Royal Veterinary College, Hertfordshire, United Kingdom, 2 Multiple Sclerosis Research Center of New York, New York, New York, United States of America Abstract The development of antibodies effective in crossing the blood brain barrier (BBB), capable of accessing the cytosol of affected cells and with higher affinity for PrPSc would be of paramount importance in arresting disease progression in its late stage and treating individuals with prion diseases. Antibody-based therapy appears to be the most promising approach following the exciting report from White and colleagues, establishing the ‘‘proof-of-principle’’ for prion-immunotherapy. After passive transfer, anti-prion antibodies were shown to be very effective in curing peripheral but not central rodent prion disease, due to the fact that these anti-prion antibodies are relatively large molecules and cannot therefore cross the BBB. Here, we show that an anti-prion antibody derived from camel immunised with murine scrapie material adsorbed to immunomagnetic beads is able to prevent infection of susceptible N2a cells and cure chronically scrapie-infected neuroblastoma cultures. This antibody was also shown to transmigrate across the BBB and cross the plasma membrane of neurons to target cytosolic PrPC. In contrast, treatment with a conventional anti-prion antibody derived from mouse immunised with recombinant PrP protein was unable to prevent recurrence of PrPSc rep