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 beta-amyloid peptide (AssP). Studies have shown that immunization with Abeta42 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 Abeta 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 Abeta epitope sequences (coding for EFGH, DAEFGH, EFGH+EFGH, and EFGH+DAEFGH) with IgG heavy chain coding region of mouse. Meanwhile, the full-length gene Abeta encoding plasmid (pV-Abeta), empty vector (pVAX) and synthetic AssP 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-AssP immunoreactivity. The results showed that all the DNA vaccine plasmids induced AssP-specific antibodies; moreover pV-GE2 and pV-Abeta 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 adjuvants. 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 on immune response. These results suggest that this immunization strategy of using Abeta epitope encoding plasmid plus BCG-DNA adjuvant may serve as the basis for developing anti-Alzheimer disease vaccines.
He
Ying
Y
Department of Medical Genetics, College of Basic Medical Sciences, Second Military Medical University, Shanghai, PR China.
Sun
Shu-Han
SH
Chen
Rui-Wen
RW
Guo
Ying-Jun
YJ
He
Xiao-Wen
XW
Huang
Li
L
Chen
Zu-Huan
ZH
Shi
Ke
K
Zhu
Wei-Jia
WJ
D023582:Alzheimer Vaccines / Q000276:immunology*; D016229:Amyloid beta-Peptides / Q000276:immunology*; D000818:Animals; D018929:Cell Culture Techniques; D016207:Cytokines / Q000378:metabolism; D004269:DNA, Bacterial / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D009163:Mycobacterium bovis / Q000235:genetics*; D010957:Plasmids / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D019444:Vaccines, DNA / Q000276:immunology*
D023582:Alzheimer Vaccines; D016229:Amyloid beta-Peptides; D016207:Cytokines; D004269:DNA, Bacterial; D000939:Epitopes; D007074:Immunoglobulin G; D019444:Vaccines, DNA; D016178:Granulocyte-Macrophage Colony-Stimulating Factor