Abstract:

To enhance anti-amyloid-beta (Aβ) antibody generation and induce a Th2 immune response, we constructed a new DNA vaccine p(Aβ3–10)10-C3d-p28.3 encoding ten repeats of Aβ3–10 and three copies of C3d-p28 as a molecular adjuvant. In this study, we administered this adjuvant intramus-cularly to female C57BL/6J mice at 8–10 weeks of age. Enzyme linked immunosorbent assay was used to detect the titer of serum anti-Aβ antibody, isotypes, and cytokines in splenic T cells. A 3- (4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay was used to detect the prolifera-tion rate of splenic T cells. Brain sections from a 12-month-old APP/PS1 transgenic mouse were used for detecting the binding capacities of anti-Aβ antibodies to Aβ plaques. The p(Aβ3–10)10-C3d-p28.3 vaccine induced high titers of anti-amyloid-β antibodies, which bound to Aβ plaques in APP/PS1 transgenic mouse brain tissue, demonstrating that the vaccine is effective against plaques in a mouse model of Alzheimer’s disease. Moreover, the vaccine elicited a pre-dominantly IgG1 humoral response and low levels of interferon-γ in ex vivo cultured splenocytes, indicating that the vaccine could shift the cellular immune response towards a Th2 phenotype. This indicated that the vaccine did not elicit a detrimental immune response and had a favorable safety profile. Our results indicate that the p(Aβ3–10)10-C3d-p28.3 vaccine is a promising immunothera-peutic option for Aβ vaccination in Alzheimer’s disease.

Key words: neural regeneration, Alzheimer’s disease, amyloid-β, C57BL/6J mice, DNA vaccine, active immunotherapy, passive immunotherapy, C3d-p28 molecular adjuvant, Th2 immune response, grants-supported paper, neuroregeneration