Is vaccination against transmissible spongiform encephalopathy feasible?
Prion diseases are a unique category of illness, affecting both animals and humans, where the underlying pathogenesis is related to a conformation change of the cellular form of a normal, self-protein called a prion protein (PrP(c) [C for cellular]) to a pathological and infectious conformation known as scrapie form (PrPsc [Sc for scrapie]). Currently, all prion diseases are without effective treatment and are universally fatal. The emergence of bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease has highlighted the need to develop possible therapies. In Alzheimer's disease (AD), which has similarities to prion diseases, both passive and active immunisation have been shown to be highly effective at preventing disease and cognitive deficits in model animals. In a human trial of active vaccination in AD, despite indications of cognitive benefits in patients with an adequate humoral response, 6% of patients developed significant complications related to excessive cell-mediated immunity. This experience highlights that immunotherapies designed to be directed against a self-antigen have to finely balance an effective humoral immune response with potential autoimmune toxicity. Many prion diseases have the gut as a portal of infectious agent entry. This makes mucosal immunisation a potentially very attractive method to partially or completely prevent prion entry across the gut barrier and to also produce a modulated immune response that is unlikely to be associated with any toxicity. The authors' recent results using an attenuated Salmonella vaccine strain expressing the prion protein show that mucosal vaccination can partially protect against prion infection from a peripheral source, suggesting the feasibility of this approach.
Wisniewski
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Department of Psychiatry, New York University School of Medicine, 560 First Avenue, New York, NY 10016, USA. thomas.wisniewski@med.nyu.edu
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D000818:Animals; D002417:Cattle; D007562:Creutzfeldt-Jakob Syndrome / Q000517:prevention & control / Q000635:transmission / Q000662:veterinary; D016643:Encephalopathy, Bovine Spongiform / Q000517:prevention & control / Q000635:transmission; D006801:Humans; D018928:Immunity, Mucosal; D017096:Prion Diseases / Q000517:prevention & control / Q000635:transmission / Q000662:veterinary*; D012608:Scrapie / Q000517:prevention & control / Q000635:transmission; D014611:Vaccination / Q000662:veterinary*; D015047:Zoonoses