Prion protein-specific antibodies for therapeutic intervention of transmissible spongiform encephalopathies

Prion diseases, also called transmissible spongiform encephalopathies, are a group of fatal neurodegenerative conditions that affect humans and a wide variety of animals. There is no therapeutic or prophylactic approach against prion diseases available at present. The causative infectious agent is the prion, also termed PrPSc, which is a pathological conformer of the cellular prion protein PrPC. Passive immunisation studies with PrPC-specific antibodies indicated that immunotherapeutic strategies directed against PrPC can prevent prion disease. In this review, putative mechanisms of antibody-mediated prion inactivation, as well as active immunisation strategies, are discussed. Special attention is given to the problem of immunological self-tolerance against PrP.