title: Diminished amyloid-beta burden in Tg2576 mice following a prophylactic oral immunization with a salmonella-based amyloid-beta 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-beta (Abeta) 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 K6Abeta(1-30). At 22-24 months of age, cortical Abeta plaque burden and total Abeta(40/42) 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 Abeta 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.
authors.affiliation: Department of Physiology and Neuroscience, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Allal
authors.initials: A
authors.lastname: Boutajangout
authors.forename: Fernando
authors.initials: F
authors.lastname: Goni
authors.forename: Elin
authors.initials: E
authors.lastname: Knudsen
authors.forename: Fernanda
authors.initials: F
authors.lastname: Schreiber
authors.forename: Ayodeji
authors.initials: A
authors.lastname: Asuni
authors.forename: David
authors.initials: D
authors.lastname: Quartermain
authors.forename: Blas
authors.initials: B
authors.lastname: Frangione
authors.forename: Alejandro
authors.initials: A
authors.lastname: Chabalgoity
authors.forename: Thomas
authors.initials: T
authors.lastname: Wisniewski
authors.forename: Einar M
authors.initials: EM
authors.lastname: Sigurdsson
mesh_terms: D000284:Administration, Oral; D000544:Alzheimer Disease / Q000517:prevention & control*; D023582:Alzheimer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016229:Amyloid beta-Peptides / Q000276:immunology*; D000818:Animals; D002543:Cerebral Hemorrhage / Q000209:etiology / Q000517:prevention & control; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007136:Immunoglobulins / Q000097:blood; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments; D012475:Salmonella / Q000235:genetics; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
chemical_list: D023582:Alzheimer Vaccines; D016229:Amyloid beta-Peptides; D007136:Immunoglobulins; D010446:Peptide Fragments; D014614:Vaccines, Synthetic