Active Immunization with DNA Vaccine Reduced Cerebral Inflammation and Improved Cognitive Ability in APP/PS1 Transgenic Mice by In Vivo Electroporation

作者：Xing, Xiao-Na; Sha, Sha; Chen, Xiao-Hong; Guo, Wan-Shu; Guo, Rong; Jiang, Tong-Zi; Cao, Yun-Peng^*

来源：Neurochemical Research, 2015, 40(5): 1032-1041.

DOI：10.1007/s11064-015-1559-4

• Alzheimer's disease
• Amyloid beta-peptide
• DNA vaccine
• Inflammation
• Interleukin-4

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.

• 出版日期2015-5
• 单位辽宁省人民医院; 中国医科大学