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寡脱氧核苷酸作为黏膜和肠胃外佐剂的潜力。

The potential of oligodeoxynucleotides as mucosal and parenteral adjuvants.

作者信息

McCluskie M J, Weeratna R D, Davis H L

机构信息

Loeb Health Research Institute at the Ottawa Hospital, 725 Parkdale Avenue, K1Y 4E9, Ottawa, Canada.

出版信息

Vaccine. 2001 Mar 21;19(17-19):2657-60. doi: 10.1016/s0264-410x(00)00496-5.

DOI:10.1016/s0264-410x(00)00496-5
PMID:11257405
Abstract

Synthetic oligodeoxynucleotides (ODN) containing immunostimulatory CpG motifs (CpG ODN) are potent adjuvants in mice when delivered by parenteral (intramuscular, subcutaneous) and mucosal (intranasal, oral and intrarectal) routes. We have recently shown that with mucosal delivery non-CpG ODN can also have immunostimulatory properties which, in contrast to the Th1-bias characteristic of CpG ODN, are predominantly Th2-like. Herein, using hepatitis B surface antigen (HBsAg) and tetanus toxoid (TT) as model antigens in BALB/c mice, we have examined a number of different ODN (CpG, non-CpG, poly-T, poly-CG) to determine their effects on immune responses after mucosal (oral) and parenteral (IM) immunizations. Our findings demonstrate that with mucosal delivery, there is a Th2-biased immunostimulatory effect that is associated with non-CpG ODN, and that the presence of CpG motifs can shift this towards a Th1 response. The adjuvant effect of non-CpG ODN was much less evident after parenteral immunization.

摘要

含有免疫刺激CpG基序的合成寡脱氧核苷酸(ODN)(CpG ODN),通过肠胃外(肌肉内、皮下)和粘膜(鼻内、口服和直肠内)途径给药时,在小鼠中是有效的佐剂。我们最近发现,通过粘膜给药,非CpG ODN也具有免疫刺激特性,与CpG ODN的Th1偏向特征相反,其主要类似Th2。在此,我们使用乙型肝炎表面抗原(HBsAg)和破伤风类毒素(TT)作为BALB/c小鼠的模型抗原,研究了多种不同的ODN(CpG、非CpG、聚T、聚CG),以确定它们在粘膜(口服)和肠胃外(肌肉注射)免疫后对免疫反应的影响。我们的研究结果表明,通过粘膜给药,存在与非CpG ODN相关的Th2偏向性免疫刺激作用,并且CpG基序的存在可将这种作用转向Th1反应。非CpG ODN的佐剂作用在肠胃外免疫后不太明显。

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