Immunotherapy for prion diseases: opportunities and obstacles

Transmissible spongiform encephalopathies (TSEs) represent a unique form of infectious disease based on the misfolding of a self-protein into a pathological conformation. While other human diseases are also attributed to protein misfolding, the TSEs are unique in their zoonotic potential and iatrogenic infectivity. These characteristics are of particular importance in the aftermath of the UK bovine spongiform encephalopathy (BSE) outbreak due to the dual concerns that a subpopulation of individuals exposed to the infectious agent may be serving as asymptomatic carriers, and that TSEs of other food animals may also threaten human health. These potentials, in addition to the ongoing baseline of familial and sporadic human prion diseases, necessitate development of effective treatment options. While TSEs represent a novel paradigm of infection, there is nevertheless the opportunity to apply traditional approaches of medicine for disease treatment and prevention, including vaccines for immunotherapy and immunoprophylaxis. However, vaccine development for TSEs is complicated by the challenges and potential dangers associated with induction of immune responses to a self-epitope, as well as the obstacles to treatment of a chronic infection through immunotherapy. The ongoing threat of TSEs to human health, together with the opportunity to apply information emerging from these investigations to other protein misfolding disorders, justifies the efforts required to overcome these obstacles.