NDLI: Biological Effects and Use of PrPSc- and PrP-Specific Antibodies Generated by Immunization with Purified Full-Length Native Mouse Prions ▿

Content Provider	PubMed Central
Author	Petsch, Benjamin Andreas, Müller-schiffmann Lehle, Anna Zirdum, Elizabeta Ingrid, Prikulis Kuhn, Franziska Raeber, Alex J. Ironside, James W. Korth, Carsten Stitz, Lothar
Copyright Year	2011
Abstract	The prion agent is the infectious particle causing spongiform encephalopathies in animals and humans and is thought to consist of an altered conformation (PrPSc) of the normal and ubiquitous prion protein PrPC. The interaction of the prion agent with the immune system, particularly the humoral immune response, has remained unresolved. Here we investigated the immunogenicity of full-length native and infectious prions, as well as the specific biological effects of the resulting monoclonal antibodies (MAbs) on the binding and clearance of prions in cell culture and in in vivo therapy. Immunization of prion knockout (Prnp0/0 ) mice with phosphotungstic acid-purified mouse prions resulted in PrP-specific monoclonal antibodies with binding specificities selective for PrPSc or for both PrPC and PrPSc. PrPSc-specific MAb W261, of the IgG1 isotype, reacted with prions from mice, sheep with scrapie, deer with chronic wasting disease (CWD), and humans with sporadic and variant Creutzfeldt-Jakob disease (CJD) in assays including a capture enzyme-linked immunosorbent assay (ELISA) system. This PrPSc-specific antibody was unable to clear prions from mouse neuroblastoma cells (ScN2a) permanently infected with scrapie, whereas the high-affinity MAb W226, recognizing both isoforms, PrPSc and PrPC, did clear prions from ScN2a cells, as determined by a bioassay. However, an attempt to treat intraperitoneally prion infected mice with full-length W226 or with a recombinant variable-chain fragment (scFv) from W226 could only slightly delay the incubation time. We conclude that (i) native, full-length PrPSc elicits a prion-specific antibody response in PrP knockout mice, (ii) a PrPSc-specific antibody had no prion-clearing effect, and (iii) even a high-affinity MAb that clears prions in vitro (W226) may not necessarily protect against prion infection, contrary to previous reports using different antibodies.
Related Links	http://dx.doi.org/10.1128/jvi.02467-10
Ending Page	4546
Page Count	9
Starting Page	4538
File Format	PDF
ISSN	0022538X
e-ISSN	10985514
Journal	Journal of Virology
Issue Number	9
Volume Number	85
Language	English
Publisher	American Society for Microbiology
Publisher Date	2011-05-01
Access Restriction	Open
Rights Holder	American Society for Microbiology
Subject Keyword	Immunology Virology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Virology Immunology Microbiology Insect Science

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