Oral, intrarectal and intranasal immunizations using CpG and non-CpG oligodeoxynucleotides as adjuvants
Oral, intrarectal and intranasal immunizations using CpG and non-CpG oligodeoxynucleotides as adjuvants
复制标题
DOI：
10.1016/s0264-410x(00)00208-5
复制
发表时间：
2000-10-15
期刊：
影响因子：
5.5
通讯作者：
Davis, HL
中科院分区：
文献类型：
--
作者：
McCluskie, MJ;Davis, HL
我们以前已经证明，合成的寡脱氧核苷酸（ODN）含有免疫刺激性CpG基序（CpG ODN）是有效的佐剂在小鼠肌肉内，鼻内和皮下途径时，提供。本文以破伤风类毒素（TT）为模型抗原，比较了CpG ODN经直肠、鼻腔和口服3种不同途径给药后诱导小鼠黏膜和全身体液免疫应答的能力。结果显示，三种途径的免疫应答存在差异，并且还揭示了非CpG“对照”ODN在用于粘膜部位时具有佐剂效应。这是出乎意料的，因为非CpG ODN在体外或胃肠外免疫后不具有这种免疫刺激作用。在口服灭活流感疫苗本身以及与TT和B型肝炎表面抗原联合给药后，进一步研究了这些发现。我们的研究结果表明，与粘膜交付，有一个Th2免疫刺激作用与硫代磷酸ODN骨干，CpG基序的存在下，这朝着Th1的反应。(C)2000爱思唯尔科技有限公司版权所有。
We have previously demonstrated that synthetic oligodeoxynucleotides (ODN) containing immunostimulatory CpG motifs (CpG ODN) are potent adjuvants in mice when delivered by intramuscular, intranasal and subcutaneous routes. Herein, using tetanus toroid (TT) as a model antigen in BALB/c mice, we compared the ability of CpG ODN to induce mucosal and systemic humoral immune responses when antigen was delivered by three different routes: intrarectal, intranasal and oral. Results showed differences in immune responses with the three routes and also revealed that non-CpG "control" ODN had adjuvant effects when used at mucosal sites. This was unexpected since non-CpG ODN do not have such immunostimulatory effects in vitro or after parenteral immunization. These findings were further investigated after oral delivery of a killed influenza vaccine on its own as well as combined with TT and hepatitis B surface antigen. Our findings demonstrate that with mucosal delivery, there is a Th2 immunostimulatory effect associated with the phosphorothioate ODN backbone, and that the presence of CpG motifs shifts this towards a Th1 response. (C) 2000 Elsevier Science Ltd. All rights reserved.