title: Abeta1-15 is less immunogenic than Abeta1-40/42 for intranasal immunization of wild-type mice but may be effective for "boosting".
abstract: Immunizing mouse models of Alzheimer's disease (AD) against beta-amyloid (Abeta) leads to a decrease in cerebral Abeta burden as well as an improvement in behavioral deficits. Circulating Abeta-antibodies may be responsible for interfering with Abeta deposition. In the present study, we attempted to initiate more robust antibody production in wild type (WT) mice. Three immunization strategies were examined: intranasal (i.n.) immunization with Abetal-15 or full-length Abeta1-40/42, i.n. administration of Abeta combined with mucosal adjuvants, native labile enterotoxin (LT) or its non-toxic form, LT(R192G), and prime-boost regimes. Using Abeta1-15 as the primary immunogen for intranasal immunization did not initiate strong antibody production. When Abeta1-15 or Abeta1-40/42 was combined with native LT or LT(R192G), antibody production was significantly increased. Nasal immunization with Abeta1-15 and native LT successfully "boosted" an immune response "primed" by an intraperitoneal (i.p.) injection of Abeta1-40/42, producing moderately high Abeta titers that remained stable for at least 6 months. Serum anti-Abeta antibodies, regardless of the length of the Abeta immunogen, consistently detected human AD plaques, had epitopes within Abeta1-15, and were predominantly of the IgG2b, IgG1, and IgG2a isotypes. The adjuvants were well-tolerated in the mice. Thus, Abeta1-15 may have potential as a safer, more cost-effective "boosting" immunogen than the full-length Abeta peptide for chronic, active Abeta immunization.
authors.affiliation: Department of Neurology, Center for Neurologic Diseases, Harvard Institutes of Medicine 622, Brigham and Women's Hospital, 77 Avenue Louis Pasteur, Boston, MA 02115-5716, USA.
authors.forename: Jodi F
authors.initials: JF
authors.lastname: Leverone
authors.forename: Edward T
authors.initials: ET
authors.lastname: Spooner
authors.forename: Herman K
authors.initials: HK
authors.lastname: Lehman
authors.forename: John D
authors.initials: JD
authors.lastname: Clements
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Lemere
mesh_terms: D000281:Administration, Intranasal; D000544:Alzheimer Disease / Q000276:immunology* / Q000517:prevention & control; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000097:blood; D000917:Antibody Formation; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007117:Immunization, Secondary; D051379:Mice; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology*; D014612:Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D016229:Amyloid beta-Peptides; D000906:Antibodies; D010446:Peptide Fragments; D014612:Vaccines; C480626:amyloid beta-protein (1-15); C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)