共 29 条
DNA vaccination can break immunological tolerance to PrP in wild-type mice and attenuates prion disease after intracerebral challenge
被引:36
作者:

Fernandez-Borges, Natalia
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机构: Edifici CReSA, Barcelona 08193, Spain

Brun, Alejandro
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h-index: 0
机构: Edifici CReSA, Barcelona 08193, Spain

Whitton, J. Lindsay
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h-index: 0
机构: Edifici CReSA, Barcelona 08193, Spain

Parra, Beatriz
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h-index: 0
机构: Edifici CReSA, Barcelona 08193, Spain

Diaz-San Segundo, Fayna
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h-index: 0
机构: Edifici CReSA, Barcelona 08193, Spain

Salguero, Francisco J.
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h-index: 0
机构: Edifici CReSA, Barcelona 08193, Spain

Torres, Juan M.
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h-index: 0
机构: Edifici CReSA, Barcelona 08193, Spain

Rodriguez, Fernando
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h-index: 0
机构: Edifici CReSA, Barcelona 08193, Spain
机构:
[1] Edifici CReSA, Barcelona 08193, Spain
[2] INIA, CISA, Madrid 28130, Spain
[3] Scripps Res Inst, Dept Mol & Integrat Neurosci, La Jolla, CA 92037 USA
关键词:
D O I:
10.1128/JVI.01210-06
中图分类号:
Q93 [微生物学];
学科分类号:
071005 ;
100705 ;
摘要:
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.
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页码:9970 / 9976
页数:7
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