Both active and passive Aβ immunotherapy could increase the clearance of Aβ and decrease the progressive cognitive decline. To enhance anti-amyloid-β (Aβ) antibody generation and induce a Th2 immune response, we constructed a new DNA vaccine [p(Aβ3-10)10C3d-p28.3]encoding ten repeats of Aβ3-10 and three copies of C3d-p28 as a molecular adjuvant and administered it intramuscularly in eight to ten week-old female C57BL/6J mice. ELISA was used to detect the titer of serum anti-Aβ antibody, isotypes and splenic T cells cytokines. MTT assay was used to detect the proliferation rate of the splenic T cells. Brain sections from a twelve-month-old APP/PS1 transgenic mouse were used for detecting the binding capability of antiAβ antibodies to Aβ plaques. The p(Aβ3-10)10C3d-p28.3 vaccine induced high titers of anti-amyloid-β antibodies which were able to bind to Aβ plaques in APP/PS1 transgenic mouse brain tissue, demonstrating that the vaccine is effective against plaques in a mouse model of AD. Moreover, the vaccine elicited a predominantly IgG1 humoral response and low levels of IFN-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 elict a detrimental immune response and had a favorble safety profile. Our results indicate that the p(Aβ3-10)10C3d-p28.3 vaccine is a promising immunotherapeutic option for Aβ vaccination in Alzheimer’s disease.