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作为黏膜佐剂的CpG寡脱氧核苷酸。

CpG oligodeoxynucleotides as mucosal adjuvants.

作者信息

Iho Sumiko, Maeyama Jun-ichi, Suzuki Fumiko

机构信息

a Host Defense Laboratory; Faculty of Medical Sciences; University of Fukui ; Yoshida-gun , Fukui , Japan.

出版信息

Hum Vaccin Immunother. 2015;11(3):755-60. doi: 10.1080/21645515.2014.1004033.

DOI:10.1080/21645515.2014.1004033
PMID:25751765
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4514178/
Abstract

Bacterial DNA comprising palindromic sequences and containing unmethylated CpG is recognized by toll-like receptor 9 of plasmacytoid dendritic cells (pDCs) and induces the production of interferon-α and chemokines, leading to the activation of a Th1 immune response. Therefore, synthetic equivalents of bacterial DNA (CpG oligodeoxynucleotides) have been developed for clinical applications. They are usually phosphorothioated for in vivo use; this approach also leads to adverse effects as reported in mouse models.Mucosal vaccines that induce both mucosal and systemic immunity received substantial attention in recent years. For their development, phosphodiester-linked oligodeoxynucleotides, including the sequence of a palindromic CpG DNA may be advantageous as adjuvants because their target pDCs are present right there, in the mucosa of the vaccination site. In addition, the probability of adverse effects is believed to be low. Here, we review the discovery of such CpG oligodeoxynucleotides and their possible use as mucosal adjuvants.

摘要

包含回文序列且含有未甲基化CpG的细菌DNA可被浆细胞样树突状细胞(pDCs)的Toll样受体9识别,并诱导干扰素-α和趋化因子的产生,从而导致Th1免疫反应的激活。因此,已经开发出细菌DNA的合成类似物(CpG寡脱氧核苷酸)用于临床应用。它们通常进行硫代磷酸化以用于体内;正如在小鼠模型中所报道的,这种方法也会导致不良反应。近年来,诱导黏膜和全身免疫的黏膜疫苗受到了广泛关注。对于它们的开发,包括回文CpG DNA序列的磷酸二酯连接寡脱氧核苷酸作为佐剂可能具有优势,因为它们的靶标pDCs就在疫苗接种部位的黏膜中。此外,不良反应的可能性被认为较低。在这里,我们综述了此类CpG寡脱氧核苷酸的发现及其作为黏膜佐剂的可能用途。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4603/4514178/138e0d34f1f6/khvi-11-03-1004033-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4603/4514178/4ef3f7d2216e/khvi-11-03-1004033-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4603/4514178/977d6bbe4fa7/khvi-11-03-1004033-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4603/4514178/43c720bb9a6e/khvi-11-03-1004033-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4603/4514178/138e0d34f1f6/khvi-11-03-1004033-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4603/4514178/4ef3f7d2216e/khvi-11-03-1004033-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4603/4514178/977d6bbe4fa7/khvi-11-03-1004033-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4603/4514178/43c720bb9a6e/khvi-11-03-1004033-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4603/4514178/138e0d34f1f6/khvi-11-03-1004033-g004.jpg

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