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Immunomodulation for prion and prion-related diseases Wisniewski T; Goni FExpert Rev Vaccines 2010[Dec]; 9 (12): 1441-52Prion diseases are a unique category of illness, affecting both animals and humans, where the underlying pathogenesis is related to a conformational change of a normal self protein called cellular prion protein to a pathological and infectious conformer known as scrapie prion protein (PrP(Sc)). Currently, all prion diseases lack effective treatment and are universally fatal. Past experiences with bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease mainly in Europe, as well as the current epidemic of chronic wasting disease in North America, have highlighted the need to develop prophylactic and/or therapeutic approaches. In Alzheimer's disease that, like prion disease, is a conformational neurodegenerative disorder, both passive and active immunization has been shown to be highly effective in model animals at preventing disease and cognitive deficits, with emerging data from human trials suggesting that this approach is able to reduce amyloid-related pathology. However, any immunomodulatory approach aimed at a self-antigen has to finely balance an effective humoral immune response with potential autoimmune toxicity. The prion diseases most commonly acquired by infection typically have the alimentary tract as a portal of infectious agent entry. This makes mucosal immunization a potentially attractive method to produce a local immune response that partially or completely prevents prion entry across the gut barrier, while at the same time producing modulated systemic immunity that is unlikely to be associated with toxicity. Our results using an attenuated Salmonella vaccine strain expressing the prion protein showed that mucosal vaccination can protect against prion infection from a peripheral source, suggesting the feasibility of this approach. It is also possible to develop active and/or passive immunomodulatory approaches that more specifically target PrP(Sc) or target the shared pathological conformer found in numerous conformational disorders. Such approaches could have a significant impact on many of the common age-associated dementias.|*Immunomodulation[MESH]|Adaptive Immunity[MESH]|Administration, Oral[MESH]|Animals[MESH]|Genetic Vectors[MESH]|Humans[MESH]|Immunity, Mucosal[MESH]|Immunologic Factors/*administration & dosage[MESH]|Prion Diseases/*immunology/*prevention & control[MESH]|Prions/*immunology/*pathogenicity[MESH]|Salmonella Vaccines/immunology[MESH]|Vaccines, Attenuated/administration & dosage[MESH] |
