Oral vaccination as a potential strategy to manage chronic wasting disease in wild cervid populations

Prion diseases are a novel class of infectious disease based in the misfolding of the cellular prion protein (PrPC) into a pathological, self-propagating isoform (PrPSc). These fatal, untreatable neurodegenerative disorders affect a variety of species causing scrapie in sheep and goats, bovine spongiform encephalopathy (BSE) in cattle, chronic wasting disease (CWD) in cervids, and Creutzfeldt-Jacob disease (CJD) in humans. Of the animal prion diseases, CWD is currently regarded as the most significant threat due its ongoing geographical spread, environmental persistence, uptake into plants, unpredictable evolution, and emerging evidence of zoonotic potential. The extensive efforts to manage CWD have been largely ineffective, highlighting the need for new disease management tools, including vaccines. Development of an effective CWD vaccine is challenged by the unique biology of these diseases, including the necessity, and associated dangers, of overcoming immune tolerance, as well the logistical challenges of vaccinating wild animals. Despite these obstacles, there has been encouraging progress towards the identification of safe, protective antigens as well as effective strategies of formulation and delivery that would enable oral delivery to wild cervids. In this review we highlight recent strategies for antigen selection and optimization, as well as considerations of various platforms for oral delivery, that will enable researchers to accelerate the rate at which candidate CWD vaccines are developed and evaluated.

Automated summary

Prion diseases are a class of infectious diseases caused by misfolded cellular prion proteins (PrPC), which propagate and result in fatal neurodegenerative disorders. Among them, chronic wasting disease (CWD) is considered the most significant threat due to its geographical spread, environmental persistence, uptake into plants, unpredictable evolution, and potential zoonotic transmission. The development of an effective CWD vaccine is challenging but recent progress in antigen selection, formulation, and oral delivery strategies has shown promising results. This review highlights these strategies to accelerate the development and evaluation of candidate CWD vaccines.