Active Immunization with DNA Vaccine Reduced Cerebral Inflammation and Improved Cognitive Ability in APP/PS1 Transgenic Mice by In Vivo Electroporation
Active Immunization with DNA Vaccine Reduced Cerebral Inflammation and Improved Cognitive Ability in APP/PS1 Transgenic Mice by In Vivo Electroporation
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DNA 疫苗主动免疫通过体内电穿孔减少 APP/PS1 转基因小鼠的脑部炎症并提高认知能力
DOI：
10.1007/s11064-015-1559-4
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发表时间：
2015-05-01
影响因子：
4.4
通讯作者：
Cao, Yun-Peng
中科院分区：
文献类型：
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作者：
Xing, Xiao-Na;Sha, Sha;Cao, Yun-Peng
淀粉样β-肽（Aβ）的聚集被认为在阿尔茨海默病（AD）的疾病进展中发挥着关键作用。 β淀粉样蛋白定向免疫疗法被认为是一种替代性 AD 治疗方法。在这项研究中，我们构建了一种 DNA 疫苗 p(A beta(3-10))(10)-mIL-4，编码与小鼠 IL-4 融合的 A beta(3-10) 的 10 个串联重复序列。八个月大的 APP/PS1 转基因小鼠肌内注射 p(A beta(3-10))(10)-mIL-4，然后进行体内电穿孔。使用该疫苗进行免疫可诱导高滴度的抗 Aβ 抗体并减轻行为障碍。免疫球蛋白同种型分析显示主要是 IgG1 反应，离体培养的脾细胞表现出低 IFN-γ 和高 IL-4 反应，表明 Th2 抗炎反应。免疫组织化学分析显示，p(A beta(3-10))(10)-mIL-4免疫减少了Aβ沉积，小胶质细胞吸引力显着降低，同时Aβ被清除。免疫小鼠的大脑中没有出现微出血。这些结果表明，免疫可能减少了转基因小鼠大脑中的炎症，从而提高了它们的认知能力。这种新型DNA疫苗p(A beta(3-10))(10)-mIL-4可能是治疗AD的有效免疫方法。
The aggregation of amyloid beta-peptide (A beta) is thought to play a pivotal role in the disease progression of Alzheimer's disease (AD). Amyloid beta directed immunotherapy has been considered an alternative AD treatment. In this study, we constructed a DNA vaccine, p(A beta(3-10))(10)-mIL-4, encoding ten tandem repeats of A beta(3-10) fused with mouse IL-4. Eight-month-old APP/PS1 transgenic mice were injected intramuscularly with p(A beta(3-10))(10)-mIL-4 followed by in vivo electroporation. Immunization with the vaccine induced high-titer anti-A beta antibodies and attenuated the behavior impairment. Immunoglobulin iso-typing revealed a predominantly IgG1 response and ex vivo cultured splenocytes exhibited a low IFN-gamma and high IL-4 response, indicating a Th2 anti-inflammatory response. Immunohistochemical analysis revealed that p(A beta(3-10))(10)-mIL-4 immunization decreased A beta deposition, and the microglial attraction significantly decreased accompanied by the clearance of A beta. There was no microhemorrhage in the brain of the immunized mice. These results suggest that the immunization potentially reduced the inflammation in brain of transgenic mice and therefore improved their cognitive ability. This novel DNA vaccine p(A beta(3-10))(10)-mIL-4 may be an effective immunization method as therapy for AD.