Microneedle arrays for the transcutaneous immunization of diphtheria and influenza in BALB/c mice
Microneedle arrays for the transcutaneous immunization of diphtheria and influenza in BALB/c mice
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DOI：
10.1016/j.jconrel.2009.01.025
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发表时间：
2009-05-21
影响因子：
10.8
通讯作者：
Bouwstra, J. A.
中科院分区：
文献类型：
--
作者：
Ding, Z.;Verbaan, F. J.;Bouwstra, J. A.
经皮免疫(TCI)受到大分子在皮肤上渗透性差的限制。微针阵列形成短暂的管道，增强疫苗分子通过皮肤屏障的运输，而不会有痛感。本文研究了白喉类毒素(DT)和流感亚单位疫苗两种模型抗原在小鼠体内的免疫应答。台盼蓝染色和经皮失水测定表明，电敷器能使300微米的短针有效地穿透小鼠皮肤。这些疫苗在微针处理的皮肤上局部应用霍乱毒素(CT)和不使用霍乱毒素(CT)。在DT TCI中，皮肤微针阵列的预处理对于获得稳定的免疫球蛋白和毒素中和抗体滴度至关重要。CT的加入进一步增强了免疫反应，与皮下注射AlPO4吸附的DT(DT-明矾)后观察到的水平相似。相比之下，微针阵列预处理对普通流感疫苗的免疫应答没有影响。这种反应通过纳入CT而得到显著改善，而不受微针治疗的影响。这些结果表明，DT和CT微针治疗的保护效果与DT明矾注射相当，而CT佐剂流感疫苗的保护效果优于普通疫苗。(C)2009爱思唯尔B.V.保留所有权利。
Transcutaneous immunization (TCI) is limited by poor permeation of macromolecules across the skin. Microneedle arrays form transient conduits and enhance the transport of vaccine molecules across the skin barrier without pain sensation. Here we investigated in mouse the immune responses after TO using two model antigens, diphtheria toxoid (DT) and influenza subunit vaccine. The electric applicator enabled shorter microneedle (300 mu m) to pierce mouse skin effectively, as shown by Trypan blue staining and trans-epidermal water loss measurement. The vaccines were topically applied with and without cholera toxin (CT) on microneedle-treated skin. In DT TCI, microneedle array pretreatment of the skin was essential to achieve substantial IgG and toxin-neutralizing antibody titers. Addition of CT further boosted the immune response to similar levels as observed after subcutaneous injection of AlPO4-adsorbed DT (DT-alum). In contrast, microneedle array pretreatment showed no effect on the immune response to plain influenza vaccine. This response was strongly improved by inclusion of CT, independent of microneedle treatment. These results indicate that TO of DT and CT with microneedle treatment results in comparable protection as injection of DT-alum, and TO of influenza vaccine adjuvanted with CT is superior to the injection of plain vaccine. (C) 2009 Elsevier B.V. All rights reserved.