In the phase III E.mbrace trial, the investigational nine-valent ExPEC9V vaccine failed to protect older adults against invasive E. coli disease (IED). Among more than 17,000 participants aged 60 and older with a history of urinary tract infection, the vaccine efficacy was 14.6%, with 11 cases in the vaccine group versus 13 in the placebo group. The results led to early termination of the trial and discontinuation of the vaccine.
The disappointing outcome contrasts with immunogenicity data. In a subset of 449 patients, antibody titers rose at 30 days and remained higher at day 366 in vaccinated patients, though confidence intervals overlapped for four serotypes. The researchers suggested that the immune response may have been insufficient in magnitude or quality, or that mucosal immunity and urinary tract abnormalities played a role.
Safety data showed local adverse events in 35% of vaccine recipients versus 9% of placebo recipients, and systemic vaccine-related events in 27% versus 17%, mostly mild. The study's limitations include enrollment of mostly white women and older adults, which may limit generalizability. There remain no licensed vaccines for invasive E. coli disease.