Transcutaneous immunization in auricle skin induces antigen-specific mucosal and systemic immune responses in BALB/c mice
Transcutaneous immunization in auricle skin induces antigen-specific mucosal and systemic immune responses in BALB/c mice
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耳廓皮肤经皮免疫诱导 BALB/c 小鼠抗原特异性粘膜和全身免疫反应
DOI：
10.1016/j.anl.2016.08.006
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发表时间：
2017
影响因子：
1.7
通讯作者：
Kurono Y.
中科院分区：
文献类型：
--
作者：
Nagano H.;Jimura T.;Nagano M.;Miyashita K.;Kurono Y.
经皮免疫（TCI）是一种通过在皮肤上应用局部疫苗抗原的新型疫苗接种途径。磷酸胆碱（PC）是多种病原体的结构成分，抗PC免疫应答保护小鼠免受侵袭性细菌疾病的侵害。方法用PC-钥孔血蓝蛋白（KLH）加霍乱毒素（CT）对BALB/c小鼠背部皮肤或耳廓皮肤进行TCI，观察PC对小鼠皮肤TCI的影响。每周接种一次，连续接种六周。通过ELISA测定PC特异性IgG和特异性IgG 1、IgG 2a、IgM、伊加和分泌型伊加抗体，评价免疫原性。结果耳廓TCI后血清IgG水平明显高于背部和对照组，且差异有统计学意义（P <0.05）。耳廓皮肤TCI后分泌的伊加抗体也显著高于TCI后背部皮肤和对照组的鼻、BALF、阴道和粪便样本。与对照组和背部皮肤TCI相比，耳廓皮肤TCI后PC特异性IgG 1和IgG 2a显著升高。TCI后耳廓皮肤IgG 1明显高于IgG 2a。耳廓皮肤TCI后CD 4+细胞产生的IFN-γ、IL-4和IL-10显著高于背部皮肤和对照组，而IL-5，结论在BALB/c小鼠耳廓皮肤中应用PC + CT进行TCI，可明显降低小鼠耳廓皮肤中IL-12和IL-13的表达。c小鼠是诱导向Th 2方向转移的全身和粘膜免疫应答的简单方法。
ObjectiveTranscutaneous 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.MethodsTCI 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.ResultsSerum 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.ConclusionThese 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.