Development of CpG-oligodeoxynucleotides for effective activation of rabbit TLR9 mediated immune responses.
Development of CpG-oligodeoxynucleotides for effective activation of rabbit TLR9 mediated immune responses.
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开发 CpG-寡脱氧核苷酸，用于有效激活兔 TLR9 介导的免疫反应。
DOI：
10.1371/journal.pone.0108808
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Hsu LC
中科院分区：
文献类型：
--
作者：
Chuang TH;Lai CY;Tseng PH;Yuan CJ;Hsu LC
cpg - oligo脱氧核苷酸（CpG-ODN）是一种有效的免疫刺激物，正在开发用于不同物种的佐剂。toll样受体9 （TLR9）是哺乳动物细胞中CpG-ODN的细胞受体。然而，目前用于人和小鼠细胞的含有18-24个脱氧核苷酸的CpG-ODN对兔TLR9的活性较低。利用基于细胞的激活实验，我们开发了一种CpG-ODN，该CpG-ODN在12个磷酸化修饰的脱氧核苷酸中含有GACGTT或AACGTT基序，具有对兔TLR9的强刺激活性。CpG-ODN在兔脾细胞中诱导抗原非特异性免疫反应的活性高于其他CpG-ODN。当与兔出血性疾病病毒衍生的NJ85肽混合时，它们具有增强兔体内抗原特异性T细胞激活和抗体产生的有效活性。与Freund佐剂相比，开发的CpG-ODN能够促进有效且毒性较小的抗体反应。本研究结果提示，cpg基序的选择及其长度是CpG-ODN有效激活兔TLR9介导的免疫应答的重要因素。
CpG-oligodeoxynucleotides (CpG-ODN) are potent immune stimuli being developed for use as adjuvants in different species. Toll-like receptor 9 (TLR9) is the cellular receptor for CpG-ODN in mammalian cells. The CpG-ODN with 18–24 deoxynucleotides that are in current use for human and mouse cells, however, have low activity with rabbit TLR9. Using a cell-based activation assay, we developed a type of CpG-ODN containing a GACGTT or AACGTT motif in 12 phosphorothioate-modified deoxynucleotides with potent stimulatory activity for rabbit TLR9. The developed CpG-ODN have higher activities than other developed CpG-ODN in eliciting antigen-nonspecific immune responses in rabbit splenocytes. When mixed with an NJ85 peptide derived from rabbit hemorrhagic disease virus, they had potent activities to boost an antigen-specific T cell activation and antibody production in rabbits. Compared to Freund’s adjuvant, the developed CpG-ODN are capable of boosting a potent and less toxic antibody response. The results of this study suggest that both the choice of CpG-motif and its length are important factors for CpG-ODN to effectively activate rabbit TLR9 mediated immune responses.
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