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DNA vaccination can break immunological tolerance to PrP in wild-type mice and attenuates prion disease after intracerebral challenge.

Fernandez-Borges, N, Brun, A, Whitton, JL, Parra, B, Diaz-San Segundo, F, Salguero, FJ, Torres, JM and Rodriguez, F (2006) DNA vaccination can break immunological tolerance to PrP in wild-type mice and attenuates prion disease after intracerebral challenge. J Virol, 80 (20). pp. 9970-9976.

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Abstract

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 (PrP(C)). 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.

Item Type: Article
Authors :
NameEmailORCID
Fernandez-Borges, NUNSPECIFIEDUNSPECIFIED
Brun, AUNSPECIFIEDUNSPECIFIED
Whitton, JLUNSPECIFIEDUNSPECIFIED
Parra, BUNSPECIFIEDUNSPECIFIED
Diaz-San Segundo, FUNSPECIFIEDUNSPECIFIED
Salguero, FJUNSPECIFIEDUNSPECIFIED
Torres, JMUNSPECIFIEDUNSPECIFIED
Rodriguez, FUNSPECIFIEDUNSPECIFIED
Date : October 2006
Identification Number : https://doi.org/10.1128/JVI.01210-06
Uncontrolled Keywords : Animals, Antibodies, Antigens, CD36, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Immune Tolerance, Interferon-gamma, Lymphocyte Subsets, Lysosome-Associated Membrane Glycoproteins, Mice, PrPC Proteins, PrPSc Proteins, Prion Diseases, Recombinant Fusion Proteins, T-Lymphocytes, Vaccines, DNA
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 10:08
Last Modified : 17 May 2017 10:08
URI: http://epubs.surrey.ac.uk/id/eprint/826549

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