Experimental ETVAX E. coli Vaccine Shows Promise in Phase 2 Trial
The investigational ETVAX oral vaccine showed safety and immune responses in a Gambia-based phase 2b trial for enterotoxigenic E. coli. Efficacy reached 80.6% when excluding enteroparasitic pathogens. Results support progression to a phase 3 trial in high-burden settings.
An investigational oral vaccine for enterotoxigenic E. coli (ETEC) — a major cause of diarrheal disease in young children in low-income countries — was safe and induced immune responses in a phase 2b trial, researchers reported in The Lancet Infectious Diseases. Vaccine efficacy against moderate-to-severe ETEC diarrhea reached up to 80.6% in certain analyses, supporting progression to a phase 3 trial.
The double-blind, placebo-controlled trial enrolled 4,936 children aged 6 to 18 months in Gambia, randomly assigned to receive the ETVAX vaccine or placebo at three timepoints. The primary endpoints were serious adverse events and vaccine efficacy against moderate-to-severe ETEC-positive diarrhea, excluding co-infections. Serious adverse events occurred in 1.0% of the vaccine group and 1.3% of the placebo group, with none attributed to the vaccine.
In an immunological subset of 122 children, ETVAX boosted antibodies targeting ETEC colonization factors and heat-labile toxins. While the primary efficacy analysis showed a modest 26.6% reduction in ETEC diarrhea without co-pathogens, broader definitions raised efficacy substantially. Against all moderate-to-severe ETEC diarrhea regardless of co-infections, efficacy was 48.2%. Excluding enteroparasitic pathogens, efficacy reached 80.6%, and among infants who began dosing before 9 months of age, efficacy against all such cases was 67.8%.
Developed by Scandinavian Biopharma, ETVAX is the most clinically advanced ETEC vaccine candidate. ETEC causes an estimated 75 million diarrhea episodes and up to 42,000 deaths annually in children under five in low-resource settings. The study authors noted that climate warming may increase ETEC incidence, heightening the need for a vaccine. “An ETEC vaccine could reduce illness and deaths, improve child growth, decrease health-care costs, and curb antimicrobial resistance,” they wrote.
“This study provides the first demonstration of induction of protective efficacy by ETVAX in young children who are at risk,” the authors concluded, adding that the findings support a large, multicountry phase 3 trial to confirm efficacy and enable introduction in high-burden areas.