This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Fernandez-Borges, N.
Right arrow Articles by Rodriguez, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fernandez-Borges, N.
Right arrow Articles by Rodriguez, F.

 Previous Article  |  Next Article 

Journal of Virology, October 2006, p. 9970-9976, Vol. 80, No. 20
0022-538X/06/$08.00+0     doi:10.1128/JVI.01210-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

DNA Vaccination Can Break Immunological Tolerance to PrP in Wild-Type Mice and Attenuates Prion Disease after Intracerebral Challenge

Natalia Fernandez-Borges,1 Alejandro Brun,2 J. Lindsay Whitton,3 Beatriz Parra,2 Fayna Diaz-San Segundo,2 Francisco J. Salguero,2 Juan M. Torres,2 and Fernando Rodriguez1*

Centre de Recerca en Sanitat Animal (CReSA), Campus de la UAB, Bellaterra, Barcelona 08193, Spain,1 CISA-INIA, Valdeolmos, Madrid 28130, Spain,2 Department of Molecular and Integrative Neurosciences, The Scripps Research Institute, La Jolla, California 920373

Received 9 June 2006/ Accepted 1 August 2006

Transmissible spongiform encephalopathies (TSEs) can be ameliorated by prion protein (PrP)-specific antibodies, but active immunization is complicated by immune tolerance to the normal cellular host protein (PrPC). Here, we show that DNA immunization of wild-type mice can break immune tolerance against the prion protein, resulting in the induction of PrP-specific antibody and T-cell responses. PrP immunogenicity was increased by fusion to the lysosomal targeting signal from LIMPII (lysosomal integral membrane protein type II). Although mice immunized with a PrP-LIMPII DNA vaccine showed a dramatic delay in the onset of early disease signs after intracerebral challenge, immunization against PrP also had some deleterious effects. These results clearly confirm the feasibility of using active immunization to protect against TSEs and, in the absence of effective treatments, indicate a suitable alternative for combating the spread of these diseases.

* Corresponding author. Mailing address: Edifici CReSA, Campus de la UAB, Bellaterra, Cerdanyola del Valles, Barcelona 08193, Spain. Phone: 34 935814562. Fax: 34 935814490. E-mail: Fernando.Rodriguez{at}cresa.uab.es.

Journal of Virology, October 2006, p. 9970-9976, Vol. 80, No. 20
0022-538X/06/$08.00+0     doi:10.1128/JVI.01210-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Gourdain, P., Gregoire, S., Iken, S., Bachy, V., Dorban, G., Chaigneau, T., Debiec, H., Bergot, A.-S., Renault, I., Aucouturier, P., Carnaud, C. (2009). Adoptive Transfer of T Lymphocytes Sensitized against the Prion Protein Attenuates Prion Invasion in Scrapie-Infected Mice. J. Immunol. 183: 6619-6628 [Abstract] [Full Text]  
  • Sacquin, A., Bergot, A. S., Aucouturier, P., Bruley-Rosset, M. (2008). Contribution of Antibody and T Cell-Specific Responses to the Progression of 139A-Scrapie in C57BL/6 Mice Immunized with Prion Protein Peptides. J. Immunol. 181: 768-775 [Abstract] [Full Text]  
  • Song, C.-H., Furuoka, H., Kim, C.-L., Ogino, M., Suzuki, A., Hasebe, R., Horiuchi, M. (2008). Effect of intraventricular infusion of anti-prion protein monoclonal antibodies on disease progression in prion-infected mice. J. Gen. Virol. 89: 1533-1544 [Abstract] [Full Text]  
  • Kaiser-Schulz, G., Heit, A., Quintanilla-Martinez, L., Hammerschmidt, F., Hess, S., Jennen, L., Rezaei, H., Wagner, H., Schatzl, H. M. (2007). Polylactide-Coglycolide Microspheres CoEncapsulating Recombinant Tandem Prion Protein with CpG-Oligonucleotide Break Self-Tolerance to Prion Protein in Wild-Type Mice and Induce CD4 and CD8 T Cell Responses. J. Immunol. 179: 2797-2807 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»