A new DNA vaccine fused with the C3d-p28 induces a Th2 immune response against amyloid-beta*

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Abstract

Research Highlights

In this study, we successfully constructed a new plasmid DNA vaccine, p(Aβ3-10)10-C3d-p28.3, which not only boosted therapeutic levels of anti-amyloid-beta (Aβ) antibodies but also minimized the Th1 immune response. More importantly, the antibody bound to Aβ plaques in brain tissue from a 12-month-old APP/PS1 transgenic mouse, demonstrating that p(Aβ3-10)10-C3d-p28.3 elicited anti-Aβ antibodies are effective and have a strong affinity for Aβ plaques.

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 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 proliferation 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 predominantly IgG1 humoral response and low levels of interferon-γ in ex vivo cultured splenocytes, dicating 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 immunothepeutic option for Aβ vaccination in Alzheimer's disease.

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