A nine-valent E. coli vaccine did not prevent invasive disease in older adults

Design

Phase 3, randomised, double-blind, placebo-controlled; stopped for futility (E.mbrace)

Population

17,701 adults aged 60 or older with a urinary tract infection in the past 2 years, 332 sites in 20 countries

Primary outcome

First invasive E. coli disease caused by vaccine O-serotypes

Effect

24 cases (11 vaccine, 13 placebo); vaccine efficacy 14.63% (95% CI -106.57 to 65.38)

E.mbrace randomised 17,701 adults aged 60 or older, all with a urinary tract infection in the previous two years, to a single intramuscular dose of ExPEC9V or placebo, at 332 sites in 20 countries. The vaccine targets nine O-serotypes that account for most E. coli bloodstream infections. The primary endpoint was a first invasive E. coli disease episode caused by those serotypes.

A prespecified futility analysis, done when at least 40% of the expected 53 events had occurred, found no signal of efficacy, and the trial was stopped. There were 24 cases (11 in the vaccine group and 13 with placebo), giving a vaccine efficacy of 14.6% with a 95% confidence interval of -106.6 to 65.4. The vaccine produced strong and lasting antibody responses, with more low-grade adverse events than placebo but no excess serious events, and development has been discontinued.

For clinicians, the main message is that antibody response did not predict protection, and there is no vaccine to offer against E. coli bacteraemia. The trial was funded by the manufacturers.

• No E. coli vaccine is available; do not expect one to replace prevention and early treatment
• Prevention of recurrent urinary infection still rests on hydration, review of catheters and other measures, and treating asymptomatic bacteriuria only in pregnancy and before certain urological procedures
• In older adults with sepsis, look for a urinary source and take cultures before antibiotics
• Watch for drug-resistant E. coli in local antibiograms when choosing empirical treatment

Why it matters

It is a reminder that a strong antibody response does not guarantee protection, and it closes one hope for reducing bacteraemia and antibiotic use.

Don't overread it

The trial stopped early with few events, so it excludes a large effect but cannot rule out a modest one.

The statistics, in plain English

Vaccine efficacy of 14.6% with an interval from -106.6 to 65.4 means the data could not distinguish a large benefit from considerable harm, because only 24 cases occurred when 53 were expected. Immunogenicity, meaning antibody levels, is a surrogate and here it did not predict clinical protection.

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