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A camelid anti-PrP antibody abrogates PrP replication in prion-permissive neuroblastoma cell lines.

Jones, DR, Taylor, WA, Bate, C, David, M and Tayebi, M (2010) A camelid anti-PrP antibody abrogates PrP replication in prion-permissive neuroblastoma cell lines. PLoS One, 5 (3).

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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 PrP(Sc) 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 PrP(C). In contrast, treatment with a conventional anti-prion antibody derived from mouse immunised with recombinant PrP protein was unable to prevent recurrence of PrP(Sc) replication. Furthermore, our camelid antibody did not display any neurotoxic effects following treatment of susceptible N2a cells as evidenced by TUNEL staining. These findings demonstrate the potential use of anti-prion camelid antibodies for the treatment of prion and other related diseases via non-invasive means.

Item Type: Article
Divisions : Surrey research (other units)
Authors :
Jones, DR
Taylor, WA
Bate, C
David, M
Date : 2010
DOI : 10.1371/journal.pone.0009804
Uncontrolled Keywords : Adsorption, Animals, Antibodies, Antibodies, Anti-Idiotypic, Camels, Cell Line, Tumor, Immunotherapy, In Situ Nick-End Labeling, Male, Mice, Neuroblastoma, Peptides, PrPSc Proteins, Recombinant Proteins
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 10:09
Last Modified : 24 Jan 2020 18:36

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