Aβ1-15 is less immunogenic than Aβ1-40/42 for intranasal immunization of wild-type mice but may be effective for “boosting”

• Published in: Vaccine Vol. 21; no. 17; pp. 2197 - 2206
• Main Authors: Leverone, Jodi F., Spooner, Edward T., Lehman, Herman K., Clements, John D., Lemere, Cynthia A.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 16.05.2003; Elsevier
• Subjects: Alzheimer’s disease; Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Heat-labile enterotoxin; Medical sciences; Neurology; Vaccine; β-Amyloid; β-Amyloid; LT; Vaccine; Alzheimer’s disease; Heat-labile enterotoxin; Nervous system diseases; Immunization; Immune response; Alzheimer disease; Rodentia; Intranasal administration; Cerebral disorder; Vertebrata; Mammalia; Mouse; Animal; Central nervous system disease; Degenerative disease; Amyloid
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/S0264-410X(02)00754-5

Immunizing mouse models of Alzheimer’s disease (AD) against β-amyloid (Aβ) leads to a decrease in cerebral Aβ burden as well as an improvement in behavioral deficits. Circulating Aβ-antibodies may be responsible for interfering with Aβ 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 Aβl-15 or full-length Aβ1-40/42, i.n. administration of Aβ combined with mucosal adjuvants, native labile enterotoxin (LT) or its non-toxic form, LT(R192G), and prime-boost regimes. Using Aβ1-15 as the primary immunogen for intranasal immunization did not initiate strong antibody production. When Aβ1-15 or Aβ1-40/42 was combined with native LT or LT(R192G), antibody production was significantly increased. Nasal immunization with Aβ1-15 and native LT successfully “boosted” an immune response “primed” by an intraperitoneal (i.p.) injection of Aβ1-40/42, producing moderately high Aβ titers that remained stable for at least 6 months. Serum anti-Aβ antibodies, regardless of the length of the Aβ immunogen, consistently detected human AD plaques, had epitopes within Aβ1-15, and were predominantly of the IgG2b, IgG1, and IgG2a isotypes. The adjuvants were well-tolerated in the mice. Thus, Aβ1-15 may have potential as a safer, more cost-effective “boosting” immunogen than the full-length Aβ peptide for chronic, active Aβ immunization.