DNA prime-protein boost increased the titer, avidity and persistence of anti-Aβ antibodies in wild-type mice

• Published in: Gene therapy Vol. 17; no. 2; pp. 261 - 271
• Main Authors: Davtyan, H, Mkrtichyan, M, Movsesyan, N, Petrushina, I, Mamikonyan, G, Cribbs, D H, Agadjanyan, M G, Ghochikyan, A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-02-2010; Nature Publishing Group
• Subjects: Alzheimer's disease; Amyloid beta-protein; Amyloid precursor protein; Avidity; Biomedical and Life Sciences; Biomedicine; Cell Biology; Deoxyribonucleic acid; DNA; DNA vaccines; Epitopes; Gene Expression; Gene Therapy; Health aspects; Human Genetics; Immune response; Immune response (humoral); Immunoglobulin G; Lymphocytes T; Nanotechnology; Neurodegenerative diseases; original-article; Peptides; Physiological aspects; Prevention; Proteins; Risk factors; T cells; Transgenic animals; Vaccines; β-Amyloid; United States; DNA vaccine; prime–boost regimen; β-amyloid
• ISSN: 0969-7128; 1476-5462
• DOI: 10.1038/gt.2009.140

Recently, we reported that a DNA vaccine, composed of three copies of a self B cell epitope of amyloid-β (Aβ
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) and the foreign T-cell epitope, Pan DR epitope (PADRE), generated strong anti-Aβ 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-Aβ
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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-Aβ 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 Aβ
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peptide. Thus, we showed that a heterologous prime–boost regimen could be an effective protocol for developing a potent Alzheimer's disease (AD) vaccine.