Efficacy and safety of a patch vaccine containing heat-labile toxin from Escherichia coli against travellers' diarrhoea: a phase 3, randomised, double-blind, placebo-controlled field trial in travellers from Europe to Mexico and Guatemala
Efficacy and safety of a patch vaccine containing heat-labile toxin from Escherichia coli against travellers' diarrhoea: a phase 3, randomised, double-blind, placebo-controlled field trial in travellers from Europe to Mexico and Guatemala
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DOI：
10.1016/s1473-3099(13)70297-4
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发表时间：
2014-03-01
影响因子：
56.3
通讯作者：
DuPont, Herbert L.
中科院分区：
文献类型：
--
作者：
Behrens, Ronald H.;Cramer, Jakob P.;DuPont, Herbert L.
背景产肠毒素大肠杆菌（ETEC）是引起旅行者腹泻的主要原因.我们调查了一种含有病原体不耐热毒素（LT）的皮肤贴片疫苗在前往墨西哥和危地马拉的旅行者中的有效性和安全性。（18-64岁）从德国或英国前往墨西哥或危地马拉的旅行者被分配在1：1的比例，接受含37.5 μ g ETEC LT的贴剂或安慰剂贴剂的经皮免疫接种。参与者、研究中心工作人员和进行分析的研究者对分组设盲。参与者在旅行前接种疫苗，两片疫苗间隔14天。在目的地国，参与者在日记中记录粪便排出量，并在发生腹泻时提供粪便样本用于病原体鉴定。主要终点是至少发生一次中重度腹泻（定义为24小时内出现4次或4次以上不成形粪便）的受试者比例，其中检测到ETEC肠毒素（LT和热稳定毒素[ST]）之一或两者。该研究在ClinicalTrials.gov注册，编号NCT 00993681。结果2036名参与者在2009年10月14日至2010年8月13日期间招募并随机分配，其中1016名分配接受LT贴剂，1020名分配接受安慰剂贴剂。LT贴片组的821名参与者和安慰剂组的823名参与者接受了两种疫苗接种，并在符合方案人群中进行了分析。LT贴剂组30例（3.7%，95% CI 2.5-5.2）受试者和安慰剂组46例（5.6%，4.1-7.4）受试者发生中度或重度ETEC腹泻（疫苗有效性34.6%，-2.2至58.9; p=0.0621）。LT贴剂组1015名受试者中有943名（93%）发生了9333起局部（即贴剂部位）不良事件（包括红斑、皮疹、瘙痒、色素沉着过度、疼痛、色素减退和水肿），而安慰剂组1019名受试者中有574名（56%）发生了1444起局部不良事件（P
Background Enterotoxigenic Escherichia coli (ETEC) is a major cause of travellers' diarrhoea. We investigated the efficacy and safety of a skin-patch vaccine containing the pathogen's heat-labile toxin (LT) in a population of travellers to Mexico and Guatemala.Methods In this phase 3, randomised, double-blind, placebo-controlled field trial, healthy adults (aged 18-64 years) travelling from Germany or the UK to Mexico or Guatemala were assigned in a 1:1 ratio by a dynamic electronic randomisation system to receive transcutaneous immunisation with a patch containing 37.5 mu g of ETEC LT or a placebo patch. Participants, site staff, and the investigators who did the analyses were masked to group assignment. Participants were vaccinated before travel, with two patches given 14 days apart. In the destination country, participants tracked stool output in a diary and provided stool samples for pathogen identification if diarrhoea occurred. The primary endpoint was the proportion of participants with at least one episode of moderate-to-severe diarrhoea (defined as four or more unformed stools in a 24 h period) in which either or both ETEC enterotoxins (LT and heat-stable toxin [ST]) were detected. The study is registered at ClinicalTrials.gov, number NCT00993681.Findings 2036 participants were recruited and randomly assigned between Oct 14, 2009, and Aug 13, 2010, with 1016 allocated to receive the LT patch and 1020 the placebo patch. 821 participants in the LT-patch group and 823 in the placebo group received both vaccinations and were analysed in the per-protocol population. 30 (3.7%, 95% CI 2.5-5.2) participants in the LT-patch group and 46 (5.6%, 4.1-7.4) in the placebo group had moderate or severe ETEC diarrhoea (vaccine efficacy 34.6%, -2.2 to 58.9; p=0.0621). 9333 local (ie, patch-site) adverse events (including erythema, rash, pruritus, hyperpigmentation, pain, hypopigmentation, and oedema) occurred in 943 (93%) of 1015 participants in the LT-patch group, compared with 1444 local adverse events in 574 (56%) of 1019 participants in the placebo group (p