Effects of epitopes combination and adjuvants on immune responses to anti-Alzheimer disease DNA vaccines in mice

Alzheimer disease (AD) is a neurodegenerative disorder characterized by neuropathological hallmarks including deposits of the P-amyloid peptide (A beta P). Studies have shown that immunization with A beta(42) peptide reduces both the spatial memory impairments and Alzheimer disease-like neuropathologic changes in Alzheimer disease transgenic mice, but can cause side effect of a cell-mediated autoimmune meningoencephalitis. Recently, some Studies showed that DNA vaccination Could be used to generate an antibody response to A beta Without the adverse cell-mediated immune effect. In the current Study, we generate four DNA vaccine plasmids (pV-Ge1 pV-GE2, pV-GE3, and pV-GE4) against Alzheimer disease by separately fusing A epitope sequences (coding for EFGH, DAEFGH, EFGH+EFGH, and EFGH+DAEFGH) with IgG heavy chain coding region Of Mouse. Meanwhile, the full-length gene A beta encoding plasinid (pV-A beta), empty vector (pVAX) and synthetic A beta P were also included as control. The sera of BALB/c mice immunized via intramuscular with plasmids and peptide were tested by indirect ELISA for auto-A beta P immunoreactivity. The results showed that all the DNA vaccine plasmids induced A beta P-specific antibodies; moreover pV-GE2 and pV-A beta constructs elicited higher antibody titers than other constructs (P < 0.05). To further enhance the immune response, GM-CSF encoding plasmid (pGM-CSF) and purified BCG-DNA were used as molecular adjuvant. BCG-DNA could enhance humoral and cellular immune responses Simultaneously and did not alter the phenotype of the immune responses, whereas pGM-CSF showed no obvious effect oil immune response. These results Suggest that this immunization strategy Of using A beta epitope encoding plasmid plus BCG-DNA adjuvant may serve as the basis for developing anti-Alzheimer disease vaccines.