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DNA β-Amyloid1-42 Trimer Immunization for Alzheimer Disease in a Wild-Type Mouse Model
Doris Lambracht-Washington, PhD;
Bao-Xi Qu, MD;
Min Fu;
Todd N. Eagar, PhD;
Olaf Stüve, MD, PhD;
Roger N. Rosenberg, MD
JAMA. 2009;302(16):1796-1802.
Context DNA β-amyloid1-42 (Aβ42) trimer immunization was developed to produce specific T helper 2 cell (TH2)–type antibodies to provide an effective and safe therapy for Alzheimer disease (AD) by reducing elevated levels of Aβ42 peptide that occur in the brain of patients with AD.
Objective To compare the immune response in wild-type mice after immunization with DNA Aβ42 trimer and Aβ42 peptide.
Design and Intervention Wild-type mice received either 4 µg of DNA Aβ42 trimer immunization administered with gene gun (n = 8) or intraperitoneal injection of 100 µg of human Aβ42 peptide with the adjuvant Quil A (n = 8). Titers, epitope mapping, and isotypes of the Aβ42-specific antibodies were analyzed.
Main Outcome Measures Antibody titers, mapping of binding sites (epitopes), isotype profiles of the Aβ42-specific antibodies, and T-cell activation.
Results DNA Aβ42 trimer immunization resulted in antibody titers with a mean of 15 µg 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 TH2 type of immune response (IgG1/IgG2a ratio of 10). The peptide-immunized mice showed a mixed TH1/TH2 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 Aβ42 trimer immunization protocol produced a TH2 immune response and appeared to have low potential to cause an inflammatory T-cell response.
Author Affiliations: Department of Neurology, Alzheimer's Disease Center, University of Texas Southwestern Medical Center, Dallas.
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