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耳廓皮肤经皮免疫可诱导BALB/c小鼠产生抗原特异性黏膜和全身免疫反应。

Transcutaneous immunization in auricle skin induces antigen-specific mucosal and systemic immune responses in BALB/c mice.

作者信息

Nagano Hiromi, Jimura Tomohiro, Nagano Miho, Makise Takao, Miyashita Keiichi, Kurono Yuichi

机构信息

Department of Otolaryngology and Head and Neck Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Japan.

Department of Otolaryngology and Head and Neck Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Japan.

出版信息

Auris Nasus Larynx. 2017 Aug;44(4):411-416. doi: 10.1016/j.anl.2016.08.006. Epub 2016 Sep 13.

Abstract

OBJECTIVE

Transcutaneous immunization (TCI) is a novel route of vaccination through application of a topical vaccine antigen on skin. Phosphorylcholine (PC) is a structural component of a variety of pathogens, and anti-PC immune responses protect mice against invasive bacterial diseases. The purpose of the study was to examine the effect of TCI using PC in back skin or auricle skin in BALB/c mice.

METHODS

TCI was performed in BALB/c mice in back skin or auricle skin using PC-keyhole limpet hemocyanin (KLH) plus cholera toxin (CT). Inoculations were given once each week for six consecutive weeks. Immunogenicity was evaluated by measuring PC-specific IgG and specific IgG1, IgG2a, IgM, IgA, and secretory IgA antibodies by ELISA. IL-4, IL-5, IL-10, IL-12, IL-13 and IFN-γ levels were also measured by ELISA.

RESULTS

Serum IgG after TCI in auricle skin was significantly higher than after TCI in back skin and in controls. Secretory IgA antibodies after TCI in auricle skin were also significantly higher than after TCI in back skin and in controls in nasal, BALF, vaginal and fecal samples. PC-specific IgG1 and IgG2a were significantly higher after TCI in auricle skin compared to controls and compared to TCI in back skin. IgG1 was significantly higher than IgG2a after TCI in auricle skin. Production of IFN-γ, IL-4 and IL-10 from CD4 cells was significantly higher after TCI in auricle skin than after TCI in back skin and in controls, whereas IL-5, IL-12 and IL-13 were not detected in any mice.

CONCLUSION

These results suggest that TCI in auricle skin using PC plus CT in BALB/c mice is a simple approach for induction of systemic and mucosal immune responses that are shifted in the Th2 direction.

摘要

目的

经皮免疫(TCI)是一种通过在皮肤上应用局部疫苗抗原进行疫苗接种的新途径。磷酰胆碱(PC)是多种病原体的结构成分,抗PC免疫反应可保护小鼠免受侵袭性细菌疾病的侵害。本研究的目的是检测在BALB/c小鼠背部皮肤或耳廓皮肤中使用PC进行经皮免疫的效果。

方法

在BALB/c小鼠的背部皮肤或耳廓皮肤中使用PC-钥孔戚血蓝蛋白(KLH)加霍乱毒素(CT)进行经皮免疫。连续六周每周接种一次。通过ELISA测量PC特异性IgG以及特异性IgG1、IgG2a、IgM、IgA和分泌型IgA抗体来评估免疫原性。还通过ELISA测量IL-4、IL-5、IL-10、IL-12、IL-13和IFN-γ水平。

结果

耳廓皮肤经皮免疫后的血清IgG显著高于背部皮肤经皮免疫后及对照组。在鼻腔、支气管肺泡灌洗液、阴道和粪便样本中,耳廓皮肤经皮免疫后的分泌型IgA抗体也显著高于背部皮肤经皮免疫后及对照组。与对照组相比以及与背部皮肤经皮免疫相比,耳廓皮肤经皮免疫后PC特异性IgG1和IgG2a显著更高。耳廓皮肤经皮免疫后IgG1显著高于IgG2a。耳廓皮肤经皮免疫后CD4细胞产生的IFN-γ、IL-4和IL-10显著高于背部皮肤经皮免疫后及对照组,而在任何小鼠中均未检测到IL-5、IL-12和IL-13。

结论

这些结果表明,在BALB/c小鼠的耳廓皮肤中使用PC加CT进行经皮免疫是诱导向Th2方向转变的全身和黏膜免疫反应的一种简单方法。

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