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Safety and efficacy of nasal application of CpG oligodeoxynucleotide as a mucosal adjuvant.

机译:鼻用CpG寡脱氧核苷酸作为粘膜佐剂的安全性和有效性。

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OBJECTIVES: Nasal vaccination is an effective regimen to prevent upper respiratory infections. An appropriate adjuvant is required for the development of a nasal vaccine. The safety and efficacy of CpG oligodeoxynucleotide (ODN) as a mucosal adjuvant was examined. METHODS: Mice were nasally administered various doses of CpG ODN weekly, a total of three times. Histologic changes in the spleen and the nasal mucosa were examined, and the alterations in cell subpopulations were analyzed by flow cytometry. In addition, the mice were nasally immunized with P6 outer membrane protein of nontypeable Haemophilus influenzae (NTHi) and CpG ODN, and P6-specific immune responses were examined. RESULTS: No inflammation or tissue damage was observed locally or systemically after nasal administration, even with a high dose of CpG ODN. A high dose of CpG ODN induced an increase in CD8+ T cells in the nasal mucosa and B cells in the spleen. When CpG ODN was coadministered with P6, P6-specific mucosal and systemic immune responses were effectively induced, since high levels of the specific IgA and IgG were detected in the nasal wash and serum, respectively. CONCLUSIONS: These findings suggest that CpG ODN is a safe and effective mucosal adjuvant. Further, nasal vaccination with P6 and CpG ODN might be an effective regimen to prevent upper respiratory infections.
机译:目的:鼻疫苗接种是预防上呼吸道感染的有效方法。鼻疫苗的开发需要适当的佐剂。检查了CpG寡脱氧核苷酸(ODN)作为粘膜佐剂的安全性和有效性。方法:每周对小鼠鼻腔给予不同剂量的CpG ODN,共3次。检查脾脏和鼻粘膜的组织学变化,并通过流式细胞术分析细胞亚群的变化。另外,用不可分型流感嗜血杆菌(NTHi)和CpG ODN的P6外膜蛋白经鼻免疫小鼠,并检查了P6特异性免疫应答。结果:即使高剂量的CpG ODN,经鼻给药后也未观察到局部或全身炎症或组织损伤。高剂量的CpG ODN诱导了鼻粘膜CD8 + T细胞和脾脏B细胞的增加。当CpG ODN与P6并用时,由于在鼻洗液和血清中分别检测到高水平的特异性IgA和IgG,可有效诱导P6特异性粘膜和全身免疫反应。结论:这些发现表明CpG ODN是一种安全有效的粘膜佐剂。此外,鼻腔接种P6和CpG ODN疫苗可能是预防上呼吸道感染的有效方案。

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