| Title | DNA beta-amyloid(1-42) trimer immunization for Alzheimer disease in a wild-type mouse model. | | Author(s) | Lambracht-Washington D, Qu BX, Fu M, Eagar TN, Stüve O, Rosenberg RN | | Institution | Department of Neurology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9108, USA. | | Source | JAMA 2009 Oct 28; 302(16):1796-802. | | MeSH | Adjuvants, Immunologic
Alzheimer Disease
Amyloid beta-Protein
Animals
Antibody Formation
Cytokines
Disease Models, Animal
Epitope Mapping
Female
Humans
Immunoglobulin G
Immunotherapy, Active
Mice
Peptide Fragments
Th1 Cells
Th2 Cells
Vaccines, DNA
| | 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. | | Language | eng | | Pub Type(s) | Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
| | PubMed ID | 19861672 |
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