Safety and immunogenicity of an enterotoxigenic Escherichia coli vaccine patch containing heat-labile toxin:: Use of skin pretreatment to disrupt the stratum corneum
Safety and immunogenicity of an enterotoxigenic Escherichia coli vaccine patch containing heat-labile toxin:: Use of skin pretreatment to disrupt the stratum corneum
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DOI：
10.1128/iai.01740-06
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发表时间：
2007-05-01
影响因子：
3.1
通讯作者：
Frech, Sarah A.
中科院分区：
文献类型：
--
作者：
Glenn, Gregory M.;Villar, Christina P.;Frech, Sarah A.
经皮免疫允许通过应用简单的贴片安全递送来自大肠杆菌的天然不耐热肠毒素（LT）。角质层的物理破坏可以提高递送效率。在当前研究中，在贴敷贴剂之前，使用心电图准备垫破坏角质层。使用经表皮水分损失（TEWL）的影响进行量化，并与免疫反应。在第0天和第21天，60名成人接受了来自3批LT（每组20名成人）的50 μ g LT贴剂给药。免疫耐受性良好。三个LT批次之间的抗LT免疫球蛋白G（IgG）滴度无差异;血清转化率为100%，平均抗LT IgG滴度为12，185个酶联免疫吸附测定单位（EU）（增加24倍）。发现在第二次免疫时获得的TEWL测量值与第42天抗LT IgG滴度的个体增加相关（r = 0.59，P < 0.001）。在免疫应答的比较评估中，LT+ ST+（E2447 A）口服ETEC激发后的血清（在81%的受试者中诱导中度至重度腹泻）抗LT IgG滴度为3，245 EU（增加10.8倍）。类似地，口服含霍乱毒素B亚基的霍乱疫苗（与LT交叉反应并在田间保护免受LT和LT/热稳定毒素ETEC疾病）后的抗LT IgG滴度为6，741 EU（增加3.3倍）。本研究证实，在疫苗贴剂应用前对角质层破坏的耐受性良好的方案导致与天然免疫和疫苗诱导的免疫相当的稳健免疫，并且角质层破坏的程度与免疫应答相关。
Transcutaneous immunization allows safe delivery of native heat-labile enterotoxin (LT) from Escherichia coli via application of a simple patch. Physical disruption of the stratum corneum can improve the efficiency of delivery. In the current study, the stratum corneum was disrupted using an electrocardiogram prep pad prior to patch application. The effects were quantified using transepidermal water loss (TEWL) and were correlated with the immune responses. Sixty adults received 50 mu g of LT from three lots of LT (20 adults per group) administered in a patch on days 0 and 21. The immunizations were well tolerated. There were no differences in the anti-LT immunoglobulin G (IgG) titers between the three LT lots; the seroconversion rate was 100%, and the mean anti-LT IgG titer was 12,185 enzyme-linked immunosorbent assay units (EU) (a 24-fold increase). TEWL measurements obtained at the time of the second immunization were found to correlate with the day 42 individual increases in the anti-LT IgG titer (r = 0.59, P < 0.001). In a comparative assessment of the immune responses, sera after an LT+ ST+ (E2447A) oral ETEC challenge, which induced moderate to severe diarrhea in 81% of the recipients, had anti-LT IgG titers of 3,245 EU (a 10.8-fold increase). Similarly, the anti-LT IgG titer after administration of an oral cholera toxin B subunit-containing cholera vaccine, which cross-reacts with LT and protects against LT and LT/heat-stable toxin ETEC disease in the field, was 6,741 EU (a 3.3-fold increase). This study confirmed that a well-tolerated regimen for stratum corneum disruption before vaccine patch application results in robust immunity comparable to natural immunity and vaccine-induced immunity and that the magnitude of stratum corneum disruption correlates with the immune response.