Meilahti Vaccine Research Center, MeVac, University of Helsinki and Department of Infectious Diseases, Inflammation Center, HUS, Helsinki University Hospital, Helsinki, Finland.
Human Microbiome Research Unit, University of Helsinki, Helsinki, Finland.
J Travel Med. 2023 Nov 18;30(7). doi: 10.1093/jtm/taad045.
No licensed human vaccines are available against enterotoxigenic Escherichia coli (ETEC), a major diarrhoeal pathogen affecting children in low- and middle-income countries and foreign travellers alike. ETVAX®, a multivalent oral whole-cell vaccine containing four inactivated ETEC strains and the heat-labile enterotoxin B subunit (LTB), has proved promising in Phase 1 and Phase 1/ 2 studies.
We conducted a Phase 2b double-blinded, randomized, placebo-controlled trial amongst Finnish travellers to Benin, West Africa. This report presents study design and safety and immunogenicity data. Volunteers aged 18-65 years were randomized 1:1 to receive ETVAX® or placebo. They visited Benin for 12 days, provided stool and blood samples and completed adverse event (AE) forms. IgA and IgG antibodies to LTB and O78 lipopolysaccharide (LPS) were measured by electrochemiluminescence.
The AEs did not differ significantly between vaccine (n = 374) and placebo (n = 375) recipients. Of the solicited AEs, loose stools/diarrhoea (26.7/25.9%) and stomach ache (23.0/20.0%) were reported most commonly. Of all possibly/probably vaccine-related AEs, the most frequent were gastrointestinal symptoms (54.0/48.8%) and nervous system disorders (20.3/25.1%). Serious AEs were recorded for 4.3/5.6%, all unlikely to be vaccine related. Amongst the ETVAX® recipients, LTB-specific IgA antibodies increased 22-fold. For the 370/372 vaccine/placebo recipients, the frequency of ≥2-fold increases against LTB was 81/2.4%, and against O78 LPS 69/2.7%. The majority of ETVAX® recipients (93%) responded to either LTB or O78.
This Phase 2b trial is the largest on ETVAX® undertaken amongst travellers to date. ETVAX® showed an excellent safety profile and proved strongly immunogenic, which encourages the further development of this vaccine.
目前尚无针对肠产毒性大肠杆菌（ETEC）的许可人类疫苗，ETEC 是一种主要的腹泻病原体，影响中低收入国家和外国旅行者的儿童。ETVAX®是一种包含四种灭活 ETEC 株和不耐热肠毒素 B 亚单位（LTB）的多价口服全细胞疫苗，在 1 期和 1/2 期研究中显示出良好的前景。
我们在前往西非贝宁的芬兰旅行者中进行了一项 2b 期双盲、随机、安慰剂对照试验。本报告介绍了研究设计和安全性及免疫原性数据。年龄在 18-65 岁的志愿者以 1:1 的比例随机接受 ETVAX®或安慰剂。他们在贝宁逗留 12 天，提供粪便和血液样本，并填写不良事件（AE）表。通过电化学发光法测量针对 LTB 和 O78 脂多糖（LPS）的 IgA 和 IgG 抗体。
疫苗（n=374）和安慰剂（n=375）组的不良事件无显著差异。在报告的不良事件中，稀便/腹泻（26.7/25.9%）和胃痛（23.0/20.0%）最为常见。在所有可能/很可能与疫苗相关的不良事件中，最常见的是胃肠道症状（54.0/48.8%）和神经系统疾病（20.3/25.1%）。记录到 4.3/5.6%的严重不良事件，均不太可能与疫苗相关。在 ETVAX®接受者中，LTB 特异性 IgA 抗体增加了 22 倍。在 370/372 名疫苗/安慰剂接受者中，针对 LTB 的≥2 倍增加的频率为 81/2.4%，针对 O78 LPS 的为 69/2.7%。大多数 ETVAX®接受者（93%）对 LTB 或 O78 均有反应。
这项针对旅行者的 ETVAX®最大的 2b 期试验显示出良好的安全性，并证明其具有很强的免疫原性，这鼓励进一步开发这种疫苗。
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