Prevention of scrapie pathogenesis by transgenic expression of anti-prion protein antibodies

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 pro phylaxis, attempts at vaccination have been limited by the poor immunogenic ity of prion proteins. To circumvent this, we expressed an anti-prion prote in (anti-PrP) mu chain in Prnp(o/o) mice. Transgenic mice developed sustain ed anti-PrP titers, which were not suppressed by introduction of Prnp(+) al leles. 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 immunit y was responsible for protection. This indicates the feasibility of immunol ogical inhibition of prion disease in vivo.