Hammond S A, Walwender D, Alving C R, Glenn G M
Walter Reed Army Institute of Research, Department of Membrane Biochemistry, Silver Spring, MD 20910-7500, USA.
Vaccine. 2001 Mar 21;19(17-19):2701-7. doi: 10.1016/s0264-410x(00)00506-5.
Transcutaneous immunization (TCI) is a novel immunization strategy by which antigen and adjuvant are applied topically to intact, hydrated skin to induce potent antibody and cell-mediated immune responses specific for both the antigen and the adjuvant. Using tetanus toxoid as a model antigen, we examined the T cell response to tetanus toxoid after topical immunization with a variety of adjuvants. TCI readily induced systemic antigen specific T cell responses with a mixed Th1/Th2 phenotype but with a Th2 bias. We also investigated whether priming by the intramuscular route, which is known to induce T cell memory, could be followed by a boosting immunization on the skin to induce secondary responses. TCI could augment existing immunity, but interestingly, this strategy induced potent responses only if the antibody titer was low at the time of TCI boosting. These and previous observations suggest that TCI follows known immunological principles that govern other routes of vaccine delivery. Furthermore, booster immunization using tetanus toxoid may provide a useful model for further development of important patch and formulation concepts for TCI, and act as an early candidate for validating product feasibility of TCI in humans.
经皮免疫（TCI）是一种新型免疫策略，通过将抗原和佐剂局部应用于完整、湿润的皮肤，以诱导针对抗原和佐剂的强效抗体及细胞介导的免疫反应。以破伤风类毒素作为模型抗原，我们研究了用多种佐剂进行局部免疫后对破伤风类毒素的T细胞反应。经皮免疫很容易诱导出具有混合Th1/Th2表型但以Th2为主的全身性抗原特异性T细胞反应。我们还研究了已知能诱导T细胞记忆的肌肉注射途径进行的初次免疫，之后是否可以通过皮肤加强免疫来诱导二次反应。经皮免疫可以增强现有的免疫力，但有趣的是，只有在经皮免疫加强时抗体滴度较低的情况下，这种策略才能诱导出强效反应。这些以及之前的观察结果表明，经皮免疫遵循了支配其他疫苗接种途径的已知免疫学原理。此外，使用破伤风类毒素进行加强免疫可能为经皮免疫的重要贴片和制剂概念的进一步开发提供有用的模型，并作为验证经皮免疫在人体中产品可行性的早期候选方法。
