Innovative strategies for co-delivering antigens and CpG oligonucleotides.

Innovative strategies for co-delivering antigens and CpG oligonucleotides.
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DOI:
10.1016/j.addr.2008.12.013
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发表时间:
2009-03-28
影响因子:
16.1
通讯作者:
Salem AK
Salem AK
中科院分区:
医学1区
文献类型:
--
作者:
Krishnamachari Y;Salem AK

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胞嘧啶-硫代磷酸-鸟嘌呤寡脱氧核苷酸 (CpG ODN) 是一类最新的免疫刺激佐剂,包含与细菌 DNA 中常见的类似的未甲基化 CpG 二核苷酸序列。 CpG ODN 特异性触发 Toll 样受体 9 (TLR9​​),该受体存在于树突状细胞 (DC) 等抗原呈递细胞 (APC) 的吞噬内体中。 CpG ODN 触发 DC 的激活和成熟,并有助于增加抗原的表达。 CpG ODN 可用于诱导极化 Th1 型免疫反应。多项研究表明,抗原和 CpG ODN 必须共定位于同一 APC 中,才能产生最有效的治疗性抗原特异性免疫反应。递送载体可用于确保将抗原和 CpG ODN 共同递送至相同的 APC,并显着增加 APC 的摄取。这些策略可产生比单独施用抗原高 5 至 500 倍的抗原特异性免疫反应。在这篇综述中,我们讨论了几种最新的创新策略,将抗原和 CpG ODN 佐剂共同递送至 APC。这些方法包括利用缀合物分子、多组分纳米棒、脂质体、可生物降解的微粒、脉冲释放芯片和细胞-微粒混合体。
Cytosine-phosphorothioate-guanine oligodeoxynucleotides (CpG ODN) is a recent class of immunostimulatory adjuvants that includes unmethylated CpG dinucleotide sequences similar to those commonly found in bacterial DNA. CpG ODN specifically triggers toll like receptor 9 (TLR9), which is found within phagoendosomes of antigen presenting cells (APCs) such as dendritic cells (DCs). CpG ODN triggers activation and maturation of DCs and helps to increase expression of antigens. CpG ODN can be used to induce polarized Th1 type immune responses. Several studies have shown that antigens and CpG ODN must be co-localized in the same APC to generate the most potent therapeutic antigen-specific immune responses. Delivery vehicles can be utilized to ensure co-delivery of antigens and CpG ODN to the same APCs and to significantly increase uptake by APCs. These strategies can result in antigen-specific immune responses that are 5 to 500-fold greater than administration of antigen alone. In this review, we discuss several recent and innovative strategies to co-delivering antigens and CpG ODN adjuvants to APCs. These approaches include the utilization of conjugate molecules, multi-component nanorods, liposomes, biodegradable microparticles, pulsatile release chips and cell-microparticle hybrids.
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