Hossain M Jahangir, Svennerholm Ann-Mari, Carlin Nils, D'Alessandro Umberto, Wierzba Thomas F
Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Fajara, Banjul P.O. Box 273, The Gambia.
Department of Microbiology and Immunology, Gothenburg University Research Institute (GUVAX), Gothenburg University, 40530 Gothenburg, Sweden.
Microorganisms. 2023 Dec 31;12(1):90. doi: 10.3390/microorganisms12010090.
For the first time in over 20 years, an Enterotoxigenic (ETEC) vaccine candidate, ETVAX, has advanced into a phase 2b field efficacy trial for children 6-18 months of age in a low-income country. ETVAX is an inactivated whole cell vaccine that has gone through a series of clinical trials to provide a rationale for the design elements of the Phase 2b trial. This trial is now underway in The Gambia and will be a precursor to an upcoming pivotal phase 3 trial. To reach this point, numerous findings were brought together to define factors such as safe and immunogenic doses for children, and the possible benefit of a mucosal adjuvant, double mutant labile toxin (dmLT). Considering the promising but still underexplored potential of inactivated whole cells in oral vaccination, we present a perspective compiling key observations from past ETVAX trials that informed The Gambian trial design. This report will update the trial's status and explore future directions for ETEC vaccine trials. Our aim is to provide not only an update on the most advanced ETEC vaccine candidate but also to offer insights beneficial for the development of other much-needed oral whole-cell vaccines against enteric and other pathogens.
20多年来，一种候选产肠毒素大肠杆菌（ETEC）疫苗ETVAX首次在低收入国家进入针对6至18个月大儿童的2b期现场有效性试验。ETVAX是一种灭活全细胞疫苗，已经历了一系列临床试验，为2b期试验的设计要素提供了理论依据。该试验目前正在冈比亚进行，将作为即将开展的关键3期试验的先导。为了达到这一阶段，综合了众多研究结果来确定诸如儿童安全且具有免疫原性的剂量以及粘膜佐剂双突变不耐热毒素（dmLT）可能带来的益处等因素。鉴于灭活全细胞在口服疫苗中具有前景但仍未充分探索的潜力，我们呈现一篇综述，汇总过去ETVAX试验中的关键观察结果，这些结果为冈比亚试验设计提供了依据。本报告将更新该试验的状态，并探索ETEC疫苗试验的未来方向。我们的目的不仅是提供关于最先进的候选ETEC疫苗的最新情况，还为开发其他急需的针对肠道和其他病原体的口服全细胞疫苗提供有益见解。
