Neuroscience 2005 Abstract
| Presentation Number: | 325.2 |
|---|---|
| Abstract Title: | Immunization with tandem-repeat Aß1-15 peptides results in an effective humoral response and reduced cerebral Aß levels in the absence of a cellular response to full-length Aß in APP tg mice. |
| Authors: |
Maier, M.*1
; Seabrook, T. J.1
; Jiang, L.1
; Lemere, C. A.1
1Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Med. School, Boston, MA |
| Primary Theme and Topics |
Disorders of the Nervous System - Neurodegenerative and Movement Disorders -- Alzheimer's disease: APP and presenilin -- abeta |
| Session: |
325. Abeta Clearance Poster |
| Presentation Time: | Sunday, November 13, 2005 2:00 PM-3:00 PM |
| Location: | Washington Convention Center - Hall A-C, Board # SS68 |
| Keywords: | ALZHEIMER, BETA AMYLOID, ANTIBODY, COGNITION |
Amyloid beta (Aß) immunotherapy has been shown to be effective in clearing cerebral Aß and improving cognition in mouse models of Alzheimer’s disease (AD). However, an Aß vaccine clinical trial was suspended after ∽6% of the subjects developed meningoencephalitis, possibly due to a T-cell reaction against Aß. The N-terminal Aß1-15 sequence contains the B cell epitope(s) but lacks the T cell reactive sites of full-length Aß1-42. Consequently, we tested two novel immunogens encompassing a tandem repeat of two lysine-linked Aß1-15 sequences, with (R-2xAß1-15) or without (2xAß1-15) the addition of a three amino acid RGD motif, first in wildtype mice as we reported at SFN 2004 and now here, in J20 APP tg mice. Weekly, intranasal (i.n.) immunization with 50μg R-2xAß1-15 or 2xAß1-15 plus 5 μg adjuvant LT(R192G) resulted in high anti-Aß antibody titers (719±213 SEM and 1322±468 μg/ml, respectively, at week 22) consisting mainly of IgG2b, IgG1 and IgG2a isotypes. Re-stimulation of splenocytes with R-2xAß1-15 resulted in medium stimulation indices (SI = 14.1±4.5 with 50μg/ml peptide), whereas very low SI (2.7±0.4) were detected only after re-stimulation with the highest dose (50μg/ml) of Aß1-42. Immunization with R-2xAß1-15 resulted in a significant reduction of Aß immunoreactivity (74% decrease) and cerebral Aß levels (47% for insoluble Aß42, 18% for Aß40). J20 APP tg animals immunized for 22 weeks with 2xAß1-15 showed improved performance in Morris-Water-Maze behavior testing compared to adjuvant-only treated controls.
Characterization of the humoral and cellular immune responses to 3 additional short tandem repeat peptides (2xAß1-10, 2xAß1-7, and 2xAß3-9) will be presented. Our results support the possibility to generate an effective Aß vaccine that avoids a cellular immune response against Aß.
Characterization of the humoral and cellular immune responses to 3 additional short tandem repeat peptides (2xAß1-10, 2xAß1-7, and 2xAß3-9) will be presented. Our results support the possibility to generate an effective Aß vaccine that avoids a cellular immune response against Aß.
Supported by NIH grant 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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