Neuroscience 2005 Abstract
| Presentation Number: | 544.3 |
|---|---|
| Abstract Title: | A prime/boost Aβ vaccine using Aβ1-40/42 and dendrimeric Aβ1-15 peptide in APP tg mice. |
| Authors: |
Jiang, L.*1
; Seabrook, T. J.1
; Maier, M.1
; Bitan, G.2
; Lemere, C. A.1
1CND, Brigham and Women's Hospital, Boston, MA 2CA, NRB 636, 77 Avenue Louis Pasteur, 02115, |
| Primary Theme and Topics |
Disorders of the Nervous System - Neurodegenerative and Movement Disorders -- Dementia: Therapies |
| Secondary Theme and Topics | Disorders of the Nervous System<br />- Neurotoxicity, Inflammation, and Neuroprotection<br />-- Neuroprotective mechanisms and treatments |
| Session: |
544. Anti-Abeta Treatments: Animal Models I Poster |
| Presentation Time: | Monday, November 14, 2005 3:00 PM-4:00 PM |
| Location: | Washington Convention Center - Hall A-C, Board # PP26 |
| Keywords: | ALZHEIMER, AMYLOID, IMMUNOTHERAPY, IMMUNIZATION |
Amyloid β (Aβ) immunotherapy reduced cerebral Aβ in APP tg mice but resulted in meningoencephalitis in 6% of AD patients in a clinical trial (AN1792). In both mice and men, the predominant B cell epitope is located in Aβ1-15 region, while the T cell epitope is in the mid- or C-terminal region of Aβ. Thus, an Aβ immunogen containing the B cell epitope but lacking the T cell epitope may induce an effective humoral response but avoid a cellular immune response. Previously, we showed that priming with Aβ1-40/42 and boosting with Aβ1-15 resulted in anti-Aβ titers in WT mice. Here, we have extended those findings to J20 APP-tg mice by priming with Aβ1-40/42 and boosting with either Aβ1-15 or dendrimeric Aβ1-15 (dAβ1-15) peptide, composed of 16 copies of Aβ1-15 on a branched lysine core. J20 APP tg mice (4-5 mo old) received a s.c. injection of 100μg Aβ1-40/42 followed by 6 months of weekly intranasal immunization with 100μg of either Aβ1-15, dAβ1-15, or Aβ1-40/42 plus 5μg adjuvant LT(R192TG). Vehicle controls and mice treated with Aβ1-15 did not produce anti-Aβ antibodies. After 6 months, mice boosted with dAβ1-15 or Aβ1-40/42 had anti-Aβ antibody levels of 279 ± 116 (SEM) and 232 ± 82.7 μg/ml, respectively. The major antibody isotypes were IgG1 and IgG2b. In vitro Aβ re-stimulation of splenocytes from mice of all treatment groups led to low splenocyte proliferation. Cerebral Aβ levels were reduced non-significantly in both TBS and guanidine-soluble Aβ40 and Aβ42 in mice boosted with dAβ1-15 and Aβ1-40/42. Semi-quantitative analysis of immunolabeling (scale 0-4) showed a significant reduction in hippocampal Aβ plaques in mice boosted with Aβ1-40/42 (1.2 load ± 0.23 SEM) (p<0.001) or dAβ1-15 (2.1 ± 0.14) (p<0.05) compared to mice receiving LT(R192G) alone (2.8 ± 0.13). In summary, priming with Aβ1-40/42 and boosting with dAβ1-15, but not Aβ1-15 peptide, resulted in a significant humoral immune response and led to moderate reductions of cerebral Aβ in APP tg mice.
Supported by NIH AG20159 (CAL)
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2005 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2005. Online.
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