ETVAX: From Concepts to Demonstrated Clinical Efficacy

This review summarizes the development of an oral inactivated enterotoxigenic Escherichia coli (ETEC) vaccine, ETVAX, describing its progression from preclinical evaluation of vaccine components in animal models to clinical assessment of safety, immunogenicity and, ultimately, protective efficacy in first- and second-generation formulations. Multiple Phase 1 and Phase 2 clinical trials conducted, initially in Swedish adults and subsequently in adults and children in Bangladesh and several African countries (Egypt, Zambia and The Gambia), have shown that the candidate vaccines are well tolerated, safe and capable of inducing robust intestinal or intestine-derived immune responses against the included antigens in most vaccine recipients. ETVAX, developed based on the results gained from studies of the first- and second-generation candidate vaccines, comprises four inactivated E. coli strains engineered to overexpress the most prevalent colonization factors combined with a toxoid and a mucosal adjuvant. Recent trials have shown that ETVAX confers significant protection against moderate-severe ETEC-associated diarrhea in young children in The Gambia and in travelers to Benin in Africa, underscoring its potential value both for endemic populations and travelers.