DNA β-amyloid_1-42 trimer immunization for alzheimer diseaseina wild-type mouse model

Context: DNA β-amyloid_1-42 (Aβ42) trimer immunization was developed to produce specific T helper 2 cell (T_H2)-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 μ g of DNA Aβ42 trimer immunization administered with gene gun (n=8) or intraperitoneal injection of 100 μ g 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 μ g 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_H2 type of immune response (IgG1/IgG2a ratio of 10). The peptideimmunized mice showed a mixed T_H1/T_H2 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 T_H2 immune response and appeared to have low potential to cause an inflammatory T-cell response.