DNA prime-protein boost increased the titer, avidity and persistence of anti-Abeta antibodies in wild-type mice.
Recently, we reported that a DNA vaccine, composed of three copies of a self B cell epitope of amyloid-beta (Abeta(42)) and the foreign T-cell epitope, Pan DR epitope (PADRE), generated strong anti-Abeta immune responses in wild-type and amyloid precursor protein transgenic animals. Although DNA vaccines have several advantages over peptide-protein vaccines, they induce lower immune responses in large animals and humans compared with those in mice. The focus of this study was to further enhance anti-Abeta(11) immune responses by developing an improved DNA vaccination protocol of the prime-boost regimen, in which the priming step would use DNA and the boosting step would use recombinant protein. Accordingly, we generated DNA and recombinant protein-based epitope vaccines and showed that priming with DNA followed by boosting with a homologous recombinant protein vaccine significantly increases the anti-Abeta antibody responses and do not change the immunoglobulin G1 (IgG1) profile of humoral immune responses. Furthermore, the antibodies generated by this prime-boost regimen were long-lasting and possessed a higher avidity for binding with an Abeta(42) peptide. Thus, we showed that a heterologous prime-boost regimen could be an effective protocol for developing a potent Alzheimer's disease (AD) vaccine.
Department of Molecular Immunology, The Institute for Molecular Medicine, Huntington Beach, CA 92647-3652, USA.
H
H
Davtyan
M
M
Mkrtichyan
N
N
Movsesyan
I
I
Petrushina
G
G
Mamikonyan
D H
DH
Cribbs
M G
MG
Agadjanyan
A
A
Ghochikyan
D016229:Amyloid beta-Peptides / Q000276:immunology*; D000818:Animals; D000915:Antibody Affinity; D054422:Chemokine CCL22 / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000378:metabolism; D017780:Malaria Vaccines / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*; D022223:Vaccines, Subunit / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology
D016229:Amyloid beta-Peptides; D054422:Chemokine CCL22; D018984:Epitopes, T-Lymphocyte; D007074:Immunoglobulin G; D017780:Malaria Vaccines; C401223:PADRE 45; D010446:Peptide Fragments; D019444:Vaccines, DNA; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic