A nine-valent E. coli vaccine (ExPEC9V) failed to protect older adults against invasive E. coli disease in a large phase 3 trial, leading to early termination. Despite generating strong antibody responses, the vaccine showed just 14.63% efficacy — far from meaningful protection. Its development has since been discontinued.
A large, global phase 3 trial testing ExPEC9V — a nine-valent vaccine targeting invasive Escherichia coli disease (IED) — has come up short. The trial enrolled over 17,700 adults aged 60 and older with a recent history of UTIs, but a prespecified futility analysis triggered early termination after the vaccine showed just 14.63% efficacy against invasive E. coli disease in blood or sterile sites. The development of ExPEC9V has since been discontinued.
The puzzling part? The vaccine did produce robust antibody responses — with at least twofold antibody increases across all nine targeted serotypes in the vast majority of participants. That disconnect between immune response and clinical protection raises important questions about what it actually takes to prevent invasive E. coli disease.
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Why it matters: E. coli is a leading cause of bloodstream infections in older adults, and a vaccine would have been a significant public health advance. This trial's failure underscores how generating antibodies doesn't always translate to real-world protection — and highlights the need for better correlates of immunity to guide future vaccine development.
