The generation and characterization of potentially therapeutic Aβ antibodies in mice: differences according to strain and immunization protocol

• Published in: Vaccine 2002-12, Vol.21 (3), p.290-297
• Main Authors: Spooner, Edward T, Desai, Roanak V, Mori, Chica, Leverone, Jodi F, Lemere, Cynthia A
• Format: Article
• Language: English
• Subjects: Alzheimer’s disease; Aβ immunization; Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Intranasal; Medical sciences; Neurology; Vaccine
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/S0264-410X(02)00464-4

Previous studies have shown that in various mouse models of Alzheimer’s disease (AD), amyloid β-protein (Aβ) antibodies generated by Aβ peptide immunization resulted in the prevention of Aβ plaque formation in brains of young mice, decreased Aβ plaque burdens in older mice and improved cognition. The purpose of this study was to optimize Aβ immunization protocols for future trials in transgenic mouse models of AD. The timing and titers of Aβ antibody production, as well as epitope(s) and imunoglobulin isotypes, were compared between two different mouse strains (C57BL/6 and B6D2F1) and five treatment protocols: (1) chronic Aβ nasal administration, (2) repeated Aβ intraperitoneal (i.p.) injection, (3) one i.p. injection followed by chronic Aβ nasal administration, (4) chronic and concurrent Aβ nasal administration + Aβ i.p. injection, and (5) untreated controls. B6D2F1 mice generated Aβ antibodies earlier and in higher quantities than the C57BL/6 mice, indicating that B6D2F1 mice are more responsive to Aβ immunization. For both strains, mice that received the combination of Aβ nasal + Aβ i.p. injection showed the highest antibody titers. Epitope mapping experiments indicated that the mouse anti-Aβ antibodies recognize residues within Aβ1-15. Immunoglobulin isotyping demonstrated that the Aβ antibodies are of the Th-2 anti-inflammatory type, IgG1 and IgG2b, with a few IgM. Currently there is no effective therapy for Alzheimer’s disease; thus if Aβ immunization proves effective, it would be a significant step in the prevention and/or treatment of this devastating disease.