Enhancement of immune responses by DNA vaccination through targeted gene delivery using mannosylated cationic liposome formulations following intravenous administration in mice
Enhancement of immune responses by DNA vaccination through targeted gene delivery using mannosylated cationic liposome formulations following intravenous administration in mice
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DOI：
10.1016/j.bbrc.2004.03.141
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发表时间：
2004-05-14
影响因子：
3.1
通讯作者：
Hashida, M
中科院分区：
文献类型：
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作者：
Hattori, Y;Kawakami, S;Hashida, M
本研究探讨了甘露糖基化阳离子脂质体（Man脂质体），我们已经开发的新型DNA疫苗载体的效力。选择卵清蛋白（OVA）作为疫苗接种的模型抗原;因此，构建编码OVA的pDNA（pCMV-OVA）以评估DNA疫苗接种。将Man脂质体/pCMV-OVA复合物的效力与裸pCMV-OVA和与DC-Chol脂质体复合的pCMV-OVA进行比较。在体外培养的小鼠腹腔巨噬细胞中，Man脂质体/pCMV-OVA复合物的MHC I类限制性抗原提呈率显著高于裸pCMV-OVA和DC-Chol脂质体复合物。静脉给药后，OVAmRNA表达和CD 11 c（+）细胞上的MHC I类限制性抗原呈递以及可增强Man脂质体/pCMV-OVA复合物的Th 1应答的炎性细胞因子如TNF-α、IL-12和IFN-γ高于裸pCMV-OVA和与DC-Chol脂质体复合的OVAmRNA表达和MHC I类限制性抗原呈递。此外，通过静脉内施用Man脂质体/pCMV-OVA复合物免疫的小鼠的脾细胞显示出最高的增殖应答和IFN-γ分泌。这些结果表明，脂质体靶向递送DNA疫苗是一种有效的DNA疫苗治疗方法。(C)2004年爱思唯尔公司All rights reserved.
The present study investigated the potency of the mannosylated cationic liposomes (Man liposomes) that we have developed in novel DNA vaccine carrier. Ovalbumin (OVA) was selected as a model antigen for vaccination; accordingly, OVA-encoding pDNA (pCMV-OVA) was constructed to evaluate DNA vaccination. The potency of the Man liposome/pCMV-OVA complex was compared with naked pCMV-OVA and that complexed with DC-Chol liposomes. In cultured mouse peritoneal macrophages, MHC class I-restricted antigen presentation of the Man liposome/pCMV-OVA complex was significantly higher than that of naked pCMV-OVA and that complexed with DC-Chol liposomes. After intravenous administration, OVA mRNA expression and MHC class I-restricted antigen presentation on CD11c(+) cells and inflammatory cytokines, such as TNF-alpha, IL-12, and IFN-gamma, that can enhance the Th1 response of the Man liposome/pCMV-OVA complex were higher than that of naked pCMV-OVA and that complexed with DC-Chol liposomes. Also, the spleen cells from mice immunized by intravenous administration of the Man liposome/pCMV-OVA complex showed the highest proliferation response and IFN-gamma secretion. These findings suggest that the targeted delivery of DNA vaccine by Man liposomes is a potent vaccination method for DNA vaccine therapy. (C) 2004 Elsevier Inc. All rights reserved.