Development of the experimental ExPEC9V vaccine has been discontinued after a large Phase III trial demonstrated it failed to prevent invasive Escherichia coli infections in older adults. Despite generating robust immune responses, researchers found the vaccine provided no statistically established protective effect against the bacterial disease.
The Discontinuation of the E.mbrace Trial
A major Phase III study assessing a candidate vaccine meant to ward off invasive Escherichia coli infections among seniors has failed to demonstrate clinical efficacy.
It evaluated the efficacy, safety, and immunogenicity of ExPEC9V for the prevention of invasive E. coli disease in older adults. Researchers conducted the study across 20 countries.
Trial Scale and Patient Population
Between June 2021 and February 2025, the trial enrolled 17,701 participants aged 60 and older, including 8,858 receiving ExPEC9V and 8,843 receiving placebo. Participants had a history of urinary tract infections and were randomly assigned 1:1 to receive the vaccine or a placebo.
🆕💥🔴Efficacy, safety, and immunogenicity of a nine-valent vaccine (ExPEC9V) for the prevention of invasive Escherichia coli disease in older adults: a phase 3, randomised, placebo-controlled trial (E.mbrace)In this large phase 3 trial of older adults, ExPEC9V did not…
Within the per-protocol efficacy population of 17,637 individuals, 8,822 participants were assigned to the vaccine group and 8,815 were placed in the placebo group. The primary endpoint measured the incidence of invasive E. coli disease in blood or other sterile sites caused by ExPEC9V strains. ExPEC9V targets the nine E. coli O-serotypes that cause most cases of invasive disease—which occurs when the bacterium enters the bloodstream, urinary tract, or other sterile sites—in older adults. Care has grown more challenging due to drug resistance, as a cross-national investigation estimated that multidrug-resistant strains account for at least 10% of E. coli isolates found in the bloodstream.
Immune Response Versus Clinical Efficacy
Data published in The Lancet Infectious Diseases revealed that a single dose of ExPEC9V elicited a robust and sustained antibody response, with no safety concerns. Vaccines that prevent invasive E. coli disease are considered a key unmet medical need.
During the study, 24 cases of invasive disease caused by vaccine-targeted serotypes were recorded. Of these, 11 occurred among ExPEC9V recipients and 13 among placebo recipients. The estimated vaccine efficacy was 14.63% (95% CI −106.57 to 65.38), with the wide confidence interval reflecting considerable uncertainty around the efficacy estimate and demonstrating no statistically established protective effect.
Despite durability through at least the first year, the immune response did not translate into vaccine efficacy, with most IED cases occurring within year 1.
Next Steps in Evaluating Bacterial Vaccine Data
Bonten, C. Butler, and A. Edwards.
