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首页> 外文期刊>Clinical immunology: The official journal of the Clinical Immunology Society >Effective DNA epitope chimeric vaccines for Alzheimer's disease using a toxin-derived carrier protein as a molecular adjuvant
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Effective DNA epitope chimeric vaccines for Alzheimer's disease using a toxin-derived carrier protein as a molecular adjuvant

机译：使用毒素衍生的载体蛋白作为分子佐剂的有效的针对阿尔茨海默氏病的DNA表位嵌合疫苗

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摘要

Active amyloid-beta (Aβ) immunotherapy is under investigation to prevent or treat Alzheimer disease (AD). We describe here the immunological characterization and protective effect of DNA epitope chimeric vaccines using 6 copies of Aβ1-15 fused with PADRE or toxin-derived carriers. These naked 6Aβ15-T-Hc chimeric DNA vaccines were demonstrated to induce robust anti-Aβ antibodies that could recognize Aβ oligomers and inhibit Aβ oligomer-mediated neurotoxicity, result in the reduction of cerebral Aβ load and Aβ oligomers, and improve cognitive function in AD mice, but did not stimulate Aβ-specific T cell responses. Notably, toxin-derived carriers as molecular adjuvants were able to substantially promote immune responses, overcome Aβ-associated hypo-responsiveness, and elicit long-term Aβ-specific antibody response in 6Aβ15-T-Hc-immunized AD mice. These findings suggest that our 6Aβ15-T-Hc DNA chimeric vaccines can be used as a safe and effective strategy for AD immunotherapy, and toxin-derived carrier proteins are effective molecular adjuvants of DNA epitope vaccines for Alzheimer's disease.
机译：主动淀粉样蛋白（Aβ）免疫疗法正在研究中，以预防或治疗阿尔茨海默氏病（AD）。我们在这里描述了DNA抗原决定簇嵌合疫苗的免疫学特征和保护作用，该疫苗使用了6个拷贝的Aβ1-15与PADRE或毒素衍生载体融合而成。这些裸露的6Aβ15-T-Hc嵌合DNA疫苗被证明可诱导强大的抗Aβ抗体，该抗体可以识别Aβ寡聚体并抑制Aβ寡聚体介导的神经毒性，从而降低大脑Aβ负荷和Aβ寡聚体，并改善AD的认知功能小鼠，但是没有刺激Aβ特异性T细胞反应。值得注意的是，毒素衍生的载体作为分子佐剂能够在6Aβ15-T-Hc免疫的AD小鼠中显着促进免疫反应，克服与Aβ相关的低反应性并引发长期的Aβ特异性抗体反应。这些发现表明我们的6Aβ15-T-HcDNA嵌合疫苗可以用作AD免疫疗法的安全有效策略，并且毒素衍生的载体蛋白是用于阿尔茨海默氏病的DNA表位疫苗的有效分子佐剂。

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