In:
Journal of Virology, American Society for Microbiology, Vol. 85, No. 9 ( 2011-05), p. 4538-4546
Abstract:
The prion agent is the infectious particle causing spongiform encephalopathies in animals and humans and is thought to consist of an altered conformation (PrP Sc ) of the normal and ubiquitous prion protein PrP C . 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 ( Prnp 0/0 ) mice with phosphotungstic acid-purified mouse prions resulted in PrP-specific monoclonal antibodies with binding specificities selective for PrP Sc or for both PrP C and PrP Sc . PrP Sc -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 PrP Sc -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, PrP Sc and PrP C , 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 PrP Sc elicits a prion-specific antibody response in PrP knockout mice, (ii) a PrP Sc -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.
Type of Medium:
Online Resource
ISSN:
0022-538X
,
1098-5514
DOI:
10.1128/JVI.02467-10
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2011
detail.hit.zdb_id:
1495529-5
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