Recent developments in mucosal vaccines against prion diseases.

Bovine spongiform encephalopathy in cattle is highly suspected to be orally transmitted to humans through contaminated food, causing new variant Creutzfeldt-Jakob disease. However, no prophylactic procedures against these diseases, such as vaccines, in particular those stimulating mucosal protective immunity, have been established. The causative agents of these diseases, termed prions, consist of the host-encoded prion protein (PrP). Therefore, prions are immunologically tolerated, inducing no host antibody responses. This immune tolerance to PrP has hampered the development of vaccines against prions. We and others recently reported that the immune tolerance could be successfully broken and mucosal immunity could be stimulated by mucosal immunization of mice with PrP fused with bacterial enterotoxin or delivered using an attenuated Salmonella strain, eliciting significantly higher immunoglobulin A and G antibody responses against PrP. In this review, we will discuss these reports.