Department of Pharmaceutical Sciences, College of Pharmacy Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR, USA.
J Pharm Pharmacol. 2011 Feb;63(2):199-205. doi: 10.1111/j.2042-7158.2010.01219.x.
Non-invasive immunization by application of plasmid DNA topically onto the skin is an attractive immunization approach. However, the immune responses induced are generally weak. Previously, we showed that the antibody responses induced by topical DNA vaccine are significantly enhanced when hair follicles in the application area are induced into the anagen (growth) stage by hair plucking. In the present study, we further investigated the mechanism of immune enhancement.
Three different methods--hair plucking or treatment with retinoic acid (RA) or O-tetradecanoylphorbol-13-acetate (TPA)--were used to induce mice hair follicles into the anagen stage before they were dosed with a β-galactosidase-encoding plasmid, and the specific antibody responses induced were evaluated.
The hair-plucking method was more effective at enhancing the resultant antibody responses. Treatment with RA or TPA caused more damage to the skin and induced more severe local inflammation than hair plucking. However, hair plucking was most effective at enhancing the uptake or retention of the DNA in the application area.
The uptake of plasmid DNA in the application area correlated with the antibody responses induced by a topically applied DNA.
将质粒 DNA 经皮局部应用于皮肤进行非侵入性免疫接种是一种很有吸引力的免疫接种方法。然而，所诱导的免疫反应通常较弱。以前，我们发现通过拔毛将应用区域的毛囊诱导进入生长期，可显著增强经皮 DNA 疫苗诱导的抗体反应。在本研究中，我们进一步研究了免疫增强的机制。
在给小鼠施用编码β-半乳糖苷酶的质粒之前，使用三种不同的方法（拔毛、用视黄酸（RA）或十四烷酰佛波醇-13-乙酸酯（TPA）处理）将毛囊诱导进入生长期，并评估所诱导的特异性抗体反应。
拔毛法在增强抗体反应方面更有效。与拔毛相比，RA 或 TPA 处理对皮肤造成更大的损伤，并引起更严重的局部炎症。然而，拔毛最有效地促进了应用区域中 DNA 的摄取或保留。
应用区域中质粒 DNA 的摄取与经皮应用 DNA 诱导的抗体反应相关。
