Institute for Immunology, University Medical Center, Johannes Gutenberg University, Langenbeckstr. 1, 55131 Mainz, Germany.
3rd Dept. of Medicine, University Medical Center, Johannes Gutenberg University, Langenbeckstr. 1, 55131 Mainz, Germany.
J Dermatol Sci. 2017 Sep;87(3):260-267. doi: 10.1016/j.jdermsci.2017.07.018. Epub 2017 Aug 12.
Transcutaneous immunization (TCI) is a non-invasive vaccination strategy targeting the skin-associated lymphoid tissue. Topical application of the TLR7 agonist imiquimod as adjuvant in combination with peptide antigens activates the innate immune system and mounts cytotoxic T lymphocyte (CTL) responses.
Based on the commercial 5% imiquimod-containing drug Aldara we aimed to develop an improved formulation with superior vaccination efficiencies. The primary target was the enhancement of mast cell activation as important key for the function of the innate immune system.
We investigated the effects of 9-phenanthrol (9-phe) on the activation of mast cells in vitro and in vivo. For TCI, we applied 0.2% 9-phe in Aldara or Aldara alone as adjuvants in combination with the MHC class I - restricted peptide SIINFEKL. To monitor vaccination, mast cell degranulation, migration of DC and frequencies of epitope-specific CTL was assessed. In a transgenic tumor model, the efficiencies of prophylactic immunization against a tumor antigen were also monitored.
9-phe induced degranulation of mast cells in vitro and upon topical application in vivo. A mixture of 0.2% 9-phe in Aldara showed superior results regarding the migration of DC and the expansion of antigen-specific CTL. Consequently, prophylactic immunization with 0.2% 9-phe in Aldara caused enhanced protection against tumor inoculation.
Our data demonstrate that a simple modification of an adjuvant formulation can yield superior results in experimental vaccination protocols by boosting critical steps leading to the generation of an efficient CTL response.
经皮免疫（TCI）是一种针对皮肤相关淋巴组织的非侵入性疫苗接种策略。TLR7 激动剂咪喹莫特作为佐剂局部应用于肽抗原可激活固有免疫系统并引发细胞毒性 T 淋巴细胞（CTL）反应。
基于市售的 5%咪喹莫特乳膏 Aldara，我们旨在开发一种具有更高疫苗效率的改良配方。主要目标是增强肥大细胞的激活，因为这是固有免疫系统功能的重要关键。
我们研究了 9-菲（9-phe）对体外和体内肥大细胞激活的影响。对于 TCI，我们将 0.2%9-phe 应用于 Aldara 或 Aldara 作为佐剂与 MHC Ⅰ类限制肽 SIINFEKL 联合使用。为了监测疫苗接种，评估了肥大细胞脱颗粒、DC 迁移和表位特异性 CTL 的频率。在转基因肿瘤模型中，还监测了针对肿瘤抗原的预防性免疫接种的效率。
9-phe 在体外诱导肥大细胞脱颗粒，在体内局部应用时也诱导肥大细胞脱颗粒。0.2%9-phe 与 Aldara 的混合物在 DC 迁移和抗原特异性 CTL 的扩增方面显示出更好的结果。因此，用 0.2%9-phe 与 Aldara 进行预防性免疫接种可增强对肿瘤接种的保护作用。
我们的数据表明，通过增强导致有效 CTL 反应产生的关键步骤，佐剂配方的简单修饰可以在实验性疫苗接种方案中产生更好的结果。
