Diminished Amyloid-β Burden in Tg2576 Mice Following a Prophylactic Oral Immunization with a Salmonella-Based Amyloid-β Derivative Vaccine

Abstract

Immunotherapy holds great promise for Alzheimer's disease (AD) and other conformational disorders but certain adverse reactions need to be overcome. Prior to the side effects in the first Elan/Wyeth AD vaccine trial, we proposed using amyloid-β (Aβ) derivatives as a safer approach. The route of administration may also affect vaccine safety. To assess the feasibility of oral immunization that promotes mucosal immunity, Tg2576 AD model mice were treated prophylactically three times over 6 weeks starting at 3–5 months of age with a Salmonella vaccine expressing K6Aβ_1-30. At 22–24 months of age, cortical Aβ plaque burden and total Aβ₄₀/₄₂ levels were reduced by 48–75% in the immunized mice compared to controls, which received unmodified Salmonella. Plaque clearance was not associated with increased microglial activation, which may be explained by the long treatment period. Furthermore, cerebral microhemorrhages were not increased in the treated mice in contrast to several passive Aβ antibody studies. These results further support our findings with this immunogen delivered subcutaneously and demonstrate its efficacy when given orally, which may provide added benefits for human use.