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Prevention of Scrapie Pathogenesis by Transgenic Expression of Anti-Prion Protein Antibodies

Science  05 Oct 2001:
Vol. 294, Issue 5540, pp. 178-182
DOI: 10.1126/science.1063093

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Abstract

Variant Creutzfeldt-Jakob disease and bovine spongiform encephalopathy are initiated by extracerebral exposure to prions. Although prion transmission from extracerebral sites to the brain represents a potential target for prophylaxis, attempts at vaccination have been limited by the poor immunogenicity of prion proteins. To circumvent this, we expressed an anti-prion protein (anti-PrP) μ chain in Prnp o/o mice. Transgenic mice developed sustained anti-PrP titers, which were not suppressed by introduction ofPrnp + alleles. Transgene expression prevented pathogenesis of prions introduced by intraperitoneal injection in the spleen and brain. Expression of endogenous PrP (PrPC) in the spleen and brain was unaffected, suggesting that immunity was responsible for protection. This indicates the feasibility of immunological inhibition of prion disease in vivo.

  • * These authors contributed equally to this work.

  • To whom correspondence should be addressed. E-mail: adriano{at}pathol.unizh.ch

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