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脂质体包裹 CpG-DNA 激活 Toll 样受体 9 并产生表位特异性抗体。

Activation of Toll-like receptor 9 and production of epitope specific antibody by liposome-encapsulated CpG-DNA.

机构信息

Department of Microbiology, College of Medicine, Hallym University, Chuncheon 200-702, Korea.

出版信息

BMB Rep. 2011 Sep;44(9):607-12. doi: 10.5483/bmbrep.2011.44.9.607.

DOI:10.5483/bmbrep.2011.44.9.607
PMID:21944255
Abstract

Several investigators have shown that CpG-DNA has outstanding effects as a Th1-responsive adjuvant and that its potent adjuvant effects are enhanced by encapsulation with a liposome of proper composition. In this study, we showed that encapsulation with phosphatidyl-Β-oleoyl-γ-palmitoyl ethanolamine (DOPE): cholesterol hemisuccinate (CHEMS) complex enhances the immunostimulatory activity of CpG DNA and the binding of CpG-DNA to TLR9. We also examined involvement of myeloid differentiation protein (MyD88) and NF-κB activation in liposome-encapsulated CpG-DNA-induced IL-8 promoter activation. In this manuscript, the natural phosphodiester bond CpG-DNA encapsulated by DOPE : CHEMS complex is designated as Lipoplex(O). Importantly, we successfully screened B cell epitopes of envelope protein (E protein) of hepatitis C virus (HCV-E) and attachment glycoprotein G of human respiratory syncytial virus (HRSV-G) by immunization with complexes of several peptides and Lipoplex(O) without carriers. Therefore, Lipoplex(O) is potentially applicable as a universal adjuvant for peptide-based epitope screening and antibody production.

摘要

一些研究人员已经表明,CpG-DNA 作为 Th1 反应性佐剂具有出色的效果,并且通过用适当组成的脂质体包裹,可以增强其有效的佐剂效果。在这项研究中,我们表明,用磷脂酰-β-油酰基-γ-棕榈酰乙醇胺(DOPE):胆固醇半琥珀酸酯(CHEMS)复合物包裹可以增强 CpG DNA 的免疫刺激性活性和 CpG-DNA 与 TLR9 的结合。我们还研究了髓样分化蛋白(MyD88)和 NF-κB 激活在脂质体包裹的 CpG-DNA 诱导的 IL-8 启动子激活中的参与。在本文中,用 DOPE:CHEMS 复合物包裹的天然磷酸二酯键 CpG-DNA 被指定为 Lipoplex(O)。重要的是,我们成功地通过用几种肽和 Lipoplex(O)的复合物免疫筛选了丙型肝炎病毒(HCV-E)包膜蛋白(E 蛋白)和人类呼吸道合胞病毒(HRSV-G)附着糖蛋白 G 的 B 细胞表位,而无需载体。因此,Lipoplex(O)有可能作为基于肽的表位筛选和抗体生产的通用佐剂。

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