TOPLINE

A nine-valent vaccine (ExPEC9V) did not demonstrate efficacy against invasive Escherichia coli disease (IED) caused by the targeted E coli serotypes in older adults with a history of urinary tract infection (UTI). The vaccine efficacy against the first episode of IED in blood or other sterile sites was 14.63% (95% CI, -106.57% to 65.38%), and a prespecified futility analysis led to the early termination of the trial.

METHODOLOGY

• Researchers conducted a phase 3, randomized, double-blind, placebo-controlled trial at 332 clinical sites in 20 countries to assess the efficacy, safety, and immunogenicity of the ExPEC9V vaccine.
• They included 17,701 participants aged 60 years or older with a history of UTI within the previous 2 years; the participants were randomly assigned to receive either a single intramuscular dose of ExPEC9V (n = 8858) or placebo (n = 8843). The full analysis set comprised 17,694 participants (median age, 70.0 years; 70.6% women).
• The primary endpoint was the first episode of IED in blood or other sterile sites caused by ExPEC9V O-serotypes (O1A, O2, O4, O6A, O15, O16, O18A, O25B, and O75), with onset 29 days or more after vaccination, evaluated in the per-protocol efficacy population (n = 17,637).
• Secondary endpoints included the first episode of IED in blood, other sterile sites, or in urine; the first episode of pyelonephritis; and the first episode of UTI, each caused by ExPEC9V O-serotypes. Additionally, immunogenicity was assessed in a subset of 1168 participants.
• The participants were to be followed up for up to 48 months for infection events through self-reporting, site contacts, and visits, but the study ended early, and the average follow-up per participant was 540.5 days in the ExPEC9V group and 543.9 days in the placebo group.

TAKEAWAY

• In the per-protocol efficacy population, 13 IED events occurred in the placebo group and 11 in the ExPEC9V group, yielding a vaccine efficacy of 14.63% (95% CI, -106.57 to 65.38), which indicated no protective effect of the vaccine against the primary endpoint.
• Because the primary endpoint was not met, the efficacy of the vaccine could not be established for the secondary endpoints; for the first pyelonephritis event caused by ExPEC9V O-serotypes, vaccine efficacy was 46.75% (95% CI, 4.66-71.15), but this result was descriptive only and could not be tested statistically.
• ExPEC9V induced robust binding antibody responses, with geometric mean ratios at day 30 ranging from 4.60 for O75 to 32.30 for O2. At least twofold increases in antibody concentrations were observed for all nine O-serotypes, with the percentages of participants who experienced these increases ranging from 77% (177 of 231; O4) to 97% (224 of 231; O2).
• In the safety subset (n = 3713), solicited local adverse events were reported in 35% (648 of 1851) of the ExPEC9V recipients vs 9% (173 of 1862) of the placebo recipients, and most events were grade 1 or 2; in the full analysis set (n = 17,694), serious adverse events occurred within 180 days in 5% of the participants in each group, with no vaccine-related deaths.

IN PRACTICE

"ExPEC9V did not demonstrate efficacy in the prevention of IED in older adults with a history of UTI, and the development of this vaccine has been discontinued. As vaccine-induced antibodies to ExPEC9V were observed in serum, future analyses will assess correlations between binding and functional antibodies and their levels in individual IED cases and controls," the authors of the study wrote.

SOURCE

The study was led by Marc Bonten, MD, Julius Center, UMC Utrecht, Utrecht University, Utrecht, Netherlands. It was published online on October 12, 2026, in The Lancet Infectious Diseases.

LIMITATIONS

The study enrolled only older adults, with approximately 70% women and 70% White participants, which might have limited generalizability. Immunogenicity testing was conducted in a subset, and functional antibody levels were not analyzed in the full immunogenicity subset due to early study termination. The study did not assess E coli colonization or other immune measures such as neutrophils and T-cell responses.

DISCLOSURES

The study was funded by Johnson & Johnson and Sanofi. Thirteen authors declared being employees of Johnson & Johnson, and nine of them held stock or stock options in the company. One author holds stock options in both Johnson & Johnson and Sanofi. Multiple authors reported grants, consulting fees, or advisory board participation from various pharmaceutical companies, including Merck, GSK, Pfizer, Shionogi, and others. Additional author disclosures are reported in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.