Abstract
OBJECTIVES: The primary objectives of this study are to (1) summarise the current landscape of ETEC vaccine development by describing, characterising and comparing ETEC vaccine candidates in clinical development, (2) assess key characteristics of the phases 1, 2 and 3 clinical trials that have been designed to evaluate ETEC vaccines in development and (3) compare ETEC vaccine candidates being evaluated in clinical trials to the WHO Preferred Product Characteristics (PPC) for an ETEC vaccine. METHODS: To identify vaccine candidates, we searched 24 trial registries and PubMed. Searches were completed on 6 February 2024 and updated on 27 September 2024. We extracted information about the characteristics of each vaccine candidate and information about the most recently registered clinical trial for candidates in active development. We qualitatively synthesised the information available and compared each vaccine candidate to the WHO PPC. RESULTS: Our search returned 262 trial records and 821 publications, from which we identified 13 unique vaccine candidates with clinical development spanning three decades, with six vaccine candidates that had at least one clinical trial registered in 2014 or later. These six candidates (dmLT, dscCfAE, ETVAX, CssBA, CVD1208S-122 and ShigETEC) are in Phase 1 or Phase 2 trials with sample sizes from 50 to 4936 participants, with no Phase 3 trials registered by September 2024. Trials take place in the United States, Bangladesh and the Gambia. The candidates vary in their route of administration (oral, intradermal, intramuscular). Two candidates are being evaluated as two doses with or without a booster, and four require three doses. Three candidates are adjuvanted. Most trials are evaluating endpoints about safety and reactogenicity. CONCLUSIONS: We identified diverse ETEC vaccine candidates. Comparison with the PPC emphasised differences in approach and the limited information available from early-stage trials, and the importance of generating evidence for populations with a high burden of ETEC diarrhoea.