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Originally published in Science Express on 6 September 2001
Science 5 October 2001:
Vol. 294. no. 5540, pp. 178 - 182
DOI: 10.1126/science.1063093
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Reports

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

Frank L. Heppner,1* Christine Musahl,1* Isabelle Arrighi,1 Michael A. Klein,1 Thomas Rülicke,2 Bruno Oesch,4 Rolf M. Zinkernagel,3 Ulrich Kalinke,35 Adriano Aguzzi1dagger

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 Prnpo/o mice. Transgenic mice developed sustained anti-PrP titers, which were not suppressed by introduction of Prnp+ 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.

1 Institute of Neuropathology,
2 Institute of Laboratory Animal Science,
3 Institute of Experimental Immunology, University Hospital Zurich, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland.
4 Prionics AG, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
5 European Molecular Biology Laboratory, Mouse Biology Programme, Via E. Ramarini 32, I-00016 Monterotondo (Rome), Italy.
*   These authors contributed equally to this work.

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

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