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Updated: Jun 4, 2026
Monitoring Immune Cells Trafficking Fluorescent Prion Rods Hours after Intraperitoneal Infection
Published on: November 19, 2010
Biological effects and use of PrPSc- and PrP-specific antibodies generated by immunization with purified full-length
Benjamin Petsch1, Andreas Müller-Schiffmann, Anna Lehle
1Friedrich-Loeffler-Institut, Institute of Immunology, Tuebingen, Germany. benjamin.petsch@fli.bund.de
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.
Insights
Investigating prion diseases, this study found that while native prions can elicit an antibody response, a PrP(Sc)-specific antibody showed no prion-clearing effect. High-affinity antibodies clearing prions in vitro did not prevent infection in vivo.
Area of Science:
- Neuroscience
- Immunology
- Infectious Diseases
Background:
- Prion diseases, such as Creutzfeldt-Jakob disease (CJD), are caused by infectious prion particles (PrP(Sc)) derived from normal prion proteins (PrP(C)).
- The interaction between prions and the immune system, particularly the humoral immune response, remains poorly understood.
- Understanding this interaction is crucial for developing therapeutic strategies against prionopathies.
Purpose of the Study:
- To investigate the immunogenicity of native, infectious prions.
- To determine the biological effects of monoclonal antibodies (MAbs) against prions on prion binding and clearance.
- To evaluate the efficacy of MAbs in cell culture and in vivo prion infection models.
Main Methods:
- Immunization of prion knockout mice (Prnp(0/0)) with purified mouse prions to generate PrP-specific MAbs.
- Characterization of MAbs for binding specificity to PrP(Sc) and/or PrP(C) isoforms.
- Assessment of prion clearance in infected mouse neuroblastoma cells (ScN2a) and in vivo therapeutic efficacy in infected mice.
Main Results:
- Prion knockout mice produced PrP-specific MAbs, with some selective for PrP(Sc) and others recognizing both PrP(C) and PrP(Sc).
- A PrP(Sc)-specific MAb (W261) did not clear prions from infected cells, while a high-affinity MAb (W226) recognizing both isoforms cleared prions in vitro.
- In vivo treatment with MAb W226 or its fragment only slightly delayed the incubation period in prion-infected mice.
Conclusions:
- Native, full-length PrP(Sc) can elicit a prion-specific antibody response in PrP knockout mice.
- A PrP(Sc)-specific antibody lacks prion-clearing effects.
- High-affinity MAbs effective in clearing prions in vitro may not confer protection against prion infection in vivo.
