Could immunomodulation be used to prevent prion diseases?

Abstract

All prion diseases are currently without effective treatment and are universally fatal. The underlying pathogenesis of prion diseases (prionoses) is related to an autocatalytic conformational conversion of PrP^C (C for cellular) to a pathological and infectious conformer known as PrP^Sc (Sc for scrapie) or PrP^Res (Res for proteinase K resistant). The past experience with variant Creutzfeldt–Jakob disease, which originated from bovine spongiform encephalopathy, as well as the ongoing epidemic of chronic wasting disease has highlighted the necessity for effective prophylactic and/or therapeutic approaches. Human prionoses are most commonly sporadic, and hence therapy is primarily directed to stop progression; however, in animals the majority of prionoses are infectious and, as a result, the emphasis is on prevention of transmission. These infectious prionoses are most commonly acquired via the alimentary tract as a major portal of infectious agent entry, making mucosal immunization a potentially attractive method to produce a local immune response that can partially or completely prevent prion entry across the gut barrier, while at the same time producing a modulated systemic immunity that is unlikely to be associated with toxicity. A critical factor in any immunomodulatory methodology that targets a self-antigen is the need to delicately balance an effective humoral immune response with potential autoimmune inflammatory toxicity. The ongoing epidemic of chronic wasting disease affecting the USA and Korea, with the potential to spread to human populations, highlights the need for such immunomodulatory approaches.

Keywords::

• amyloid β
• chronic wasting disease
• conformational disorders
• Creutzfeld–Jakob disease
• oligomers
• prion
• vaccine

Financial & competing interests disclosure

This manuscript was supported by NIH grants 5R01NS047433-06A1S1, 5R01NS047433 and NS073502. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.