Adjuvant effect of multi-CpG motifs on an HIV-1 DNA vaccine

Adjuvant effect of multi-CpG motifs on an HIV-1 DNA vaccine
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DOI:
10.1016/s0264-410x(02)00238-4
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发表时间:
2002-07-26
期刊:
影响因子:
5.5
通讯作者:
Okuda, K
Okuda, K
中科院分区:
医学3区
文献类型:
--
作者:
Kojima, Y;Xin, KQ;Okuda, K

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人工合成的含有未甲基化CpG基序的寡核苷酸(ODN)可激活B细胞、NK细胞和单核/巨噬细胞,从而引发免疫反应。基于DNA疫苗的免疫原性可以通过添加CpG基序来增强的证据,我们将另外5-20个CpG基序克隆到PUC衍生的质粒中。用CpG富含的质粒体外处理骨髓来源的树突状细胞(BM-DC),可促进其MHC-II类分子、CD40和CD86活化标志物的表达。与编码HIV包膜糖蛋白的DNA疫苗一起接种于BALB/c小鼠,显著提高了HIV特异性细胞免疫和体液免疫。在DNA疫苗接种后2天或4天接种CpG质粒均有明显的促进作用。含有20个CpG拷贝的质粒在体外和体内都是最有效的免疫增强剂。这些结果表明,含有多个CpG基序的质粒可以提高DNA疫苗的免疫原性。(C)2002爱思唯尔科学有限公司。保留所有权利。
Synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs trigger an immune response characterized by the activation of B cells, NK cells and monocytes/macrophages. Based on evidence that the immunogenicity of DNA vaccines can be augmented by the addition of CpG motifs, 5-20 additional CpG motifs were cloned into a pUC-derived plasmid. Treating bone-marrow derived dendritic cells (BM-DCs) with CpG-enriched plasmids in vitro boosted their expressions of MHC class II molecules, the CD40 and CD86 activation markers. Co-administering the CpG-enriched plasmids with a DNA vaccine encoding the envelope glycoprotein of HIV to BALB/c mice significantly increased HIV-specific cell mediated and humoral immunity. A significant boost was observed when the CpG plasmid was administered either 2 or 4 days after DNA vaccination. Plasmids containing 20 CpG copies were the most effective immune enhancers both in vitro and in vivo. These results suggest that plasmids containing multiple CpG motifs may improve the immunogenicity of DNA vaccines. (C) 2002 Elsevier Science Ltd. All rights reserved.