'Promising E. Coli Vaccine Fizzles in Late-Stage Trial'

 

• There are no licensed vaccines targeting invasive E. coli disease, an acute illness that can lead to sepsis and death.
• In a phase III trial of older adults, the nine-valent ExPEC9V vaccine's efficacy rate of 14.6% indicated no protective effect against invasive E. coli disease.
• The results led to an early termination of the trial, and development of the vaccine has been discontinued.

An investigational vaccine targeting the Escherichia coli pathogens that commonly cause infections didn't show a protective effect in older adults, the phase III E.mbrace trial found.

Among over 17,000 participants ages 60 and older with a history of urinary tract infection (UTI), there were 24 cases of invasive E. coli disease (IED): 11 cases occurred in those who received the nine-valent vaccine, while 13 cases occurred in the placebo group, for a vaccine efficacy rate of 14.6% (95% CI -106.57 to 65.38), reported Monika Peeters, MSc, of Johnson & Johnson in Beerse, Belgium, and colleagues in Lancet Infectious Diseases.

The results led to an early termination of the trial, and development of the vaccine has been discontinued.

What went wrong? "In E.mbrace, systemic immunity was clearly induced," Peeters and colleagues wrote. But "with no established correlates of protection, vaccine-induced immunity might have been of insufficient magnitude or quality to provide clinical protection against IED and related events."

Caused by extraintestinal pathogenic E. coli, a common cause of UTIs and bloodstream infections, IED is an acute illness that can lead to sepsis and death, particularly in older adults. There are no licensed vaccines for IED.

The E.mbrace trial enrolled medically stable adults ages 60 and older with a history of UTI in the prior 2 years. Lower-than-expected IED incidence led the investigators to narrow the participant group to those who had at least one additional IED risk factor, such as hospitalization or urosepsis.

Patients were randomized to a single intramuscular shot of the ExPEC9V vaccine or placebo. Median patient age was 70 years; 55.4% were ages 65 to 74. Most were women (70.6%) and white (69%), and 45.7% had at least one IED risk factor.

The study's primary endpoint was the incidence of first IED event with confirmation in the blood or other sterile sites, excluding those from urine only, caused by one of the vaccine's nine E. coli serotypes at least 29 days after vaccination.

Eight of the nine vaccine serotypes were linked to IED in the vaccine and placebo groups, and efficacy was similar across demographic and clinical characteristics, including the presence of IED risk factors, geography, and age.

The investigators found that the ExPEC9V vaccine's disappointing clinical efficacy diverged from its promising immunogenicity results.

In an analysis of 449 patients, both the vaccine and placebo groups had similar pre-vaccination binding antibody levels for all nine E. coli serotypes. At 30 days, geometric mean antibody titers rose among the vaccine group while remaining flat among placebo patients. By 366 days, levels for all nine serotypes had declined but remained higher in vaccinated patients versus placebo patients. However, confidence intervals at day 366 overlapped between the two groups for four serotypes.

Failed clinical efficacy despite the immune response may reflect lack of response to the specific serotype that caused a study patient's IED, Peeters and colleagues noted. In addition, immunogenicity in the mucosa, a key entry point for pathogens driving UTIs and other infections, may have been inadequate after vaccination. Finally, urinary tract abnormalities that protect bacteria might have diminished vaccine efficacy, the researchers said.

Local adverse events occurred in 35% of the vaccine group and 9% of the placebo group, with pain, tenderness, and erythema and swelling as the most common events. Vaccine-related systemic adverse events occurred in 27% of the vaccine group and 17% of the placebo group. Most of these events were grade 1 or grade 2.

Study limitations included the inclusion of older adults only and the high percentages of female and white participants, which may limit generalizability. In addition, immunogenicity testing was conducted among a subset of participants who might not represent the full study population.

Disclosures

The study was funded by Johnson & Johnson and Sanofi.

Peeters is an employee of Johnson & Johnson.

Colleagues reported multiple relationships with industry, including Johnson & Johnson and Sanofi.

Primary Source

Lancet Infectious Diseases

Source Reference: Bonten M, et al "Efficacy, safety, and immunogenicity of a nine-valent vaccine (ExPEC9V) for the prevention of invasive Escherichia coli disease in older adults: a phase 3, randomized, placebo-controlled trial (E.mbrace)" Lancet Infect Dis 2026; DOI: 10.1016/S1473-3099(26)00469-X.

https://www.medpagetoday.com/infectiousdisease/vaccines/123400