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| Article Authors: | Doris Lambracht-Washington; Bao-Xi Qu; Min Fu; Todd N Eagar; Olaf Stüve; Roger N Rosenberg |
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| Article Title: | DNA beta-amyloid(1-42) trimer immunization for Alzheimer disease in a wild-type mouse model. |
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| Reference ID: | 1017635 |
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| Abstract: | CONTEXT: DNA beta-amyloid(1-42) (Abeta42) trimer immunization was developed to produce specific T helper 2 cell (T(H)2)-type antibodies to provide an effective and safe therapy for Alzheimer disease (AD) by reducing elevated levels of Abeta42 peptide that occur in the brain of patients with AD. OBJECTIVE: To compare the immune response in wild-type mice after immunization with DNA Abeta42 trimer and Abeta42 peptide. DESIGN AND INTERVENTION: Wild-type mice received either 4 microg of DNA Abeta42 trimer immunization administered with gene gun (n = 8) or intraperitoneal injection of 100 microg of human Abeta42 peptide with the adjuvant Quil A (n = 8). Titers, epitope mapping, and isotypes of the Abeta42-specific antibodies were analyzed. MAIN OUTCOME MEASURES: Antibody titers, mapping of binding sites (epitopes), isotype profiles of the Abeta42-specific antibodies, and T-cell activation. RESULTS: DNA Abeta42 trimer immunization resulted in antibody titers with a mean of 15 microg per milliliter of plasma. The isotype profile of the antibodies differed markedly. A predominant IgG1 antibody response was found in the DNA-immunized mice, indicating a T(H)2 type of immune response (IgG1/IgG2a ratio of 10). The peptide-immunized mice showed a mixed T(H)1/T(H)2 immune response (IgG1/IgG2a ratio of 1) (P < .001). No increased T-cell proliferation was observed in the DNA-immunized mice (P = .03). CONCLUSION: In this preliminary study in a wild-type mouse model, DNA Abeta42 trimer immunization protocol produced a T(H)2 immune response and appeared to have low potential to cause an inflammatory T-cell response. |
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| Affiliations: | Department of Neurology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9108, USA. |
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| Date: | 2009 |
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| Reference Type: | Literature |
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| PubMed ID: | 19861672 |
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| Journal: | JAMA |
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| Journal Volume: | 302 |
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| Article Pages: | 1796-802 |
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| Journal ISSN: | 1538-3598 |
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| Article Chemical List: | Adjuvants, Immunologic;Amyloid beta-Peptides;Cytokines;Immunoglobulin G;Peptide Fragments;Vaccines, DNA;amyloid beta-protein (1-42) |
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| Article MeSH List: | Adjuvants, Immunologic; Alzheimer Disease(immunology; therapy); Amyloid beta-Peptides(genetics; immunology); Animals; Antibody Formation; Cytokines(biosynthesis); Disease Models, Animal; Epitope Mapping; Female; Humans; Immunoglobulin G(immunology); Immunotherapy, Active; Mice; Peptide Fragments(genetics; immunology); Th1 Cells(immunology); Th2 Cells(immunology); Vaccines, DNA(administration & dosage; immunology; therapeutic use) |
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| Curation Last Updated: | 2013-05-28 22:00:51 |
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