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• W1993964694 abstract "A DNA vaccine remains the most attractive type of vaccine. We reported that a DNA vaccine can also be used for generating antibodies specific to the self–Aβ42 peptide (Aβ42) which plays a central role in the onset and progression of AD. More specifically, we showed that the Aβ42 fused to the IL–4 molecular adjuvant generated a potent Th2–type of immune responses in wildtype, but not in APP/Tg mice. It was not unexpected, because DNA vaccines encoded Aβ42, a self–immunogen for APP/Tg mice. To overcome this problem we developed a DNA vaccine that encodes one or three copies of the self–Aβ B cell epitope (Aβ1–11), the foreign T cell epitope (PADRE), and macrophage–derived chemokine (MDC), which can polarize the immune response towards an anti–inflammatory Th2–type phenotype. Previously, we designed and tested a second–generation of epitope vaccine (Aβ1–11–PADRE), synthesized in a multiple antigenic peptide (MAP) format. In mouse models of AD, this vaccine generated high titers of therapeutically relevant antibodies, which reduced Aβ deposits in brains of these mice. However, because the MAP backbone is not suitable for human trials, we have adopted an alternative strategy for delivering our epitope vaccine to the host immune system using DNA encoding the same immunogen (pMDC– Aβ1–11–PADRE, pMDC–3Aβ1–11–PADRE). The pMDC–3Aβ1–11–PADRE vaccine induced robust anti–Aβ antibody production and Th2 type of T cell response in 3xTg–AD mice. Testing of the therapeutic efficacy of these antibodies revealed their ability to prevent the aggregation of the Aβ42 peptide into fibrils, to disaggregate preformed fibrils, and protect embryonic neuronal cells from toxicity mediated by β–amyloid fibrils and oligomers. The effect of anti–Aβ antibodies induced by a DNA epitope vaccine on neuropathological changes in the brains of 3xTg–AD mice will be reported. Notably, the immune response to pMDC–3Aβ1–11–PADRE was far more potent than that generated in mice vaccinated with pMDC–Aβ1–11–PADRE. We will report the immune mechanisms that may explain the potency of three copies of the self–B cell epitope of Aβ42 versus one copy. The DNA epitope vaccine is a potent immunogen that could be a good candidate for clinical trials with AD patients." @default.
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• W1993964694 date "2006-07-01" @default.
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• W1993964694 title "O2-05-06: DNA-based AD epitope vaccine induced therapeutically potent anti-Aβ antibodies in AD mouse model" @default.
• W1993964694 doi "https://doi.org/10.1016/j.jalz.2006.05.143" @default.
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