Circumventing Tolerance to the Prion Protein (PrP): Vaccination with PrP-Displaying Retrovirus Particles Induces Humoral Immune Responses against the Native Form of Cellular PrP

particles displaying PrP111 (PrP D111 retroparticles) showed higher incorporation efficiencies than those displaying PrP209. Already 7 days after intravenous injection of PrP D111 retroparticles, PrP C -deficient mice (Prnp o/o ) showed high immunoglobulin M (IgM) and IgG titers specifically binding the native PrP C molecule as expressed on the surface of T cells isolated from PrP C -overexpressing transgenic mice. More importantly, heterozygous Prnp /o mice and also wild-type mice showed PrP C -specific IgM and IgG antibodies upon vaccination with PrP D111 retroparticles, albeit at considerably lower levels. Bacterially expressed recombinant PrP, in contrast, was unable to evoke IgG antibodies recognizing native PrP C in wild-type mice. Thus, our data show that PrP or parts thereof can be functionally displayed on retroviral particles and that immunization with PrP retroparticles may serve as a novel promising strategy for vaccination against transmissible spongiform encephalitis.