The University of Texas at Austin, College of Pharmacy, Pharmaceutics Division, Austin, Texas 78712, USA.
J Control Release. 2012 Jan 10;157(1):94-102. doi: 10.1016/j.jconrel.2011.08.038. Epub 2011 Sep 1.
Transcutaneous DNA immunization is an attractive immunization approach. Previously, we reported that transcutaneous immunization by applying plasmid DNA onto a skin area wherein the hair follicles had been induced into growth stage by 'cold' waxing-based hair plucking significantly enhanced the resultant immune responses. In the present study, using a plasmid that encodes the Bacillus anthracis protective antigen (PA63) gene fragment, it was shown that the anti-PA63 antibody responses induced by applying the plasmid onto a skin area where the hair was plucked by 'warm' waxing were significantly stronger than by 'cold' waxing, very likely because the 'warm' waxing-based hair depilation significantly i) enhanced the uptake (or retention) of the plasmid in the application area and ii) enhanced the expression of the transfected gene in the follicular and interfollicular epidermis in the skin. The antibody response induced by transcutaneous DNA immunization was hair cycle dependent, because the plasmid needed to be applied within 5days after the hair plucking to induce a strong antibody response. The antibody responses were not affected by whether the expressed PA63 protein, as an antigen, was secreted or cell surface bound. Finally, this strategy of enhancing the immune responses induced by transcutaneous DNA immunization following 'warm' waxing-based hair depilation was not limited to the PA63 as an antigen, because immunization with a plasmid that encodes the HIV-1 env gp160 gene induced a strong anti-gp160 response as well. Transcutaneous DNA immunization by modifying the hair follicle cycle may hold a great promise in inducing strong and functional immune responses.
经皮 DNA 免疫接种是一种很有吸引力的免疫接种方法。我们之前曾报道过，通过将质粒 DNA 应用于已通过“冷”蜡拔毛诱导进入生长阶段的毛囊区域进行经皮免疫接种，可显著增强免疫反应。在本研究中，使用编码炭疽保护性抗原（PA63）基因片段的质粒表明，通过“热”蜡拔毛将质粒应用于脱毛的皮肤区域，诱导的抗 PA63 抗体反应明显强于“冷”蜡拔毛，很可能是因为“热”蜡拔毛可显著 i）增强质粒在应用区域的摄取（或保留），以及 ii）增强转染基因在毛囊和毛囊间表皮中的表达。经皮 DNA 免疫接种引起的抗体反应依赖于毛发周期，因为在毛发拔出后 5 天内需要应用质粒才能诱导强烈的抗体反应。抗体反应不受表达的 PA63 蛋白（作为抗原）是否分泌或细胞表面结合的影响。最后，这种通过“热”蜡拔毛诱导经皮 DNA 免疫接种后增强免疫反应的策略并不局限于 PA63 作为抗原，因为用编码 HIV-1env gp160 基因的质粒免疫接种也可诱导强烈的抗 gp160 反应。通过修饰毛囊周期进行经皮 DNA 免疫接种可能在诱导强烈和功能性免疫反应方面具有很大的潜力。
