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Gene Ther. 2010 Feb;17(2):261-71. doi: 10.1038/gt.2009.140. Epub 2009 Oct 29.

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

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Department of Molecular Immunology, The Institute for Molecular Medicine, Huntington Beach, CA 92647-3652, USA.


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.

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