Güereña-Burgueño Fernando, Hall Eric R, Taylor David N, Cassels Frederick J, Scott Daniel A, Wolf Marcia K, Roberts Zachary J, Nesterova Galina V, Alving Carl R, Glenn Gregory M
Department of Enteric Infections, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910-7500, USA.
Infect Immun. 2002 Apr;70(4):1874-80. doi: 10.1128/IAI.70.4.1874-1880.2002.
Transcutaneous immunization (TCI) is a new method for vaccine delivery that has been shown to induce immunity relevant to enteric disease vaccines. We evaluated the clinical safety and immunogenicity of a recombinant subunit vaccine against enterotoxigenic Escherichia coli (ETEC) delivered by TCI. Adult volunteers received patches containing the recombinant ETEC colonization factor CS6, either with heat-labile enterotoxin (LT) or patches containing CS6 alone. The vaccine was administered at 0, 1, and 3 months, and serum antibodies and antibody-secreting cells (ASCs) were assessed. Among the 26 volunteers that completed the trial, there were no responses to CS6 in the absence of LT. In the groups receiving both CS6 and LT, 68 and 53% were found to have serum anti-CS6 immunoglobulin G (IgG) and IgA, respectively; 37 and 42% had IgG and IgA anti-CS6 ASCs. All of the volunteers receiving LT had anti-LT IgG, and 90% had serum anti-LT IgA; 79 and 37% had anti-LT IgG and IgA ASCs. Delayed-type hypersensitivity (DTH), suggesting T-cell responses, was seen in 14 of 19 volunteers receiving LT and CS6; no DTH was seen in subjects receiving CS6 alone. This study demonstrated that protein antigens delivered by a simple patch could induce significant systemic immune responses but only in the presence of an adjuvant such as LT. The data suggest that an ETEC vaccine for travelers delivered by a patch may be a viable approach worthy of further evaluation.
经皮免疫（TCI）是一种新型疫苗接种方法，已被证明可诱导与肠道疾病疫苗相关的免疫反应。我们评估了通过经皮免疫接种的抗产肠毒素大肠杆菌（ETEC）重组亚单位疫苗的临床安全性和免疫原性。成年志愿者接受含有重组ETEC定居因子CS6的贴片，或同时含有不耐热肠毒素（LT），或仅含有CS6的贴片。疫苗分别在0、1和3个月接种，并评估血清抗体和抗体分泌细胞（ASC）。在完成试验的26名志愿者中，在没有LT的情况下，对CS6无反应。在同时接受CS6和LT的组中，分别有68%和53%的志愿者血清中含有抗CS6免疫球蛋白G（IgG）和IgA；37%和42%的志愿者有抗CS6 IgG和IgA ASC。所有接受LT的志愿者均有抗LT IgG，90%的志愿者血清中有抗LT IgA；79%和37%的志愿者有抗LT IgG和IgA ASC。19名接受LT和CS6的志愿者中有14名出现迟发型超敏反应（DTH），提示有T细胞反应；仅接受CS6的受试者未出现DTH。本研究表明，通过简单贴片递送的蛋白质抗原可诱导显著的全身免疫反应，但仅在存在如LT这样的佐剂时才会出现。数据表明，通过贴片递送的旅行者ETEC疫苗可能是一种值得进一步评估的可行方法。
