High Titers of Mucosal and Systemic anti-PrP Antibodies Abrogates Oral Prion Infection in Mucosal Vaccinated Mice

Significant outbreaks of prion disease linked to oral exposure of the prion agent have occurred in animal and human populations. These disorders are associated with a conformational change of a normal protein, PrP C , to a toxic and infectious form, PrP Sc . None of the prionoses currently have an effective treatment. Some forms of prion disease are thought to be spread by oral ingestion of PrP Sc , such as chronic wasting disease and variant Creutzfeldt-Jakob disease. Attempts to obtain an active immunization in wild-type animals have been hampered by auto-tolerance to PrP and potential toxicity. Previously, we demonstrated that it is possible to overcome tolerance and obtain a specific anti-PrP antibody response by oral inoculation of the PrP protein expressed in an attenuated Salmonella vector. This past study showed that 30% of vaccinated animals were free of disease more than 350 days post-challenge. In the current study we have both optimized the vaccination protocol and divided the vaccinated mice into low and high immune responder groups prior to oral challenge with PrP Sc scrapie strain 139A. These methodological refinements lead to a significantly improved therapeutic response. 100% of mice with a high mucosal anti-PrP titer IgA and a high systemic IgG titer, prior to challenge, remained without symptoms of PrP infection at 400 days (long-rank test p