By Andrew R. Scott

Results from the first long-term follow-up study of an oral vaccine for recurrent urinary tract infections (UTIs) suggest that it “could be a gamechanger for UTI prevention,” according to consultant urologist Bob Yang, who co-led the trial.

“It’s very exciting… for us it was almost magical,” said Yang, who works with the Royal Berkshire NHS Foundation Trust. He explained that the trial, whose results are being presented at the European Association of Urology Congress (EAU) in Paris from 5 to 8 April 2024, was built on initial impressive results he and colleagues had found in private, off-licence use with a small number of patients.

‘Dramatic’

“The results were dramatic,” Yang said. “We had women who were coming month after month with infection after infection, despite all treatment, often with last-line antibiotics. And [after using the vaccine] they came back and said what have you done to us? We are infection-free.”

The vaccine, called Uromune, was developed by Immunotek S.L. in Spain. It is composed of inactivated whole bacteria commonly associated with UTIs: Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, and Enterococcus Faecalis. It is administered by two sprays of a pineapple flavoured suspension under the tongue every day for 3 months.

The vaccine has been used, largely off-licence, in some countries for several years, with short-term efficacy already supported by published trials in which Yang and his colleagues participated. But they wanted to more fully investigate if an initial vaccination regime could safely and effectively give long-lasting protection for people who experience recurrent UTIs.

Long-Term Results

That led to the 9-year follow-up, which investigated safety and long-term efficacy in 89 patients (72 women and 17 men) aged 18 to 87 (average age 56) with recurrent UTIs. These patients were originally treated privately at the Urology Partnership Reading, UK. 40% of the participants also had repeat doses of the vaccine after 1 or 2 years.

Forty-eight participants (54%) remained UTI-free during the 9-year follow up period, with an average UTI-free period for the entire cohort of 4.5 years. In terms of safety, Yang said no adverse effects or other concerns were identified.

Yang explained that one key purpose of the presentation to the EAU Congress was to subject the results to some initial peer review and feedback. Formal and full publication should then follow by the end of 2024.

‘Exciting’

Jennifer Rohn, professor of renal medicine and head of the Centre for Urological Biology at University College London, who was not involved in the research, said: "These results are exciting and suggest that preventing UTI may be one viable strategy in our fight against an infection that afflicts around 400 million people each year, mostly women, and which antibiotics struggle to control in up to 30% of those many cases.”

Rohn added that vaccination is a particularly attractive strategy in an era when bacterial infections are becoming increasingly resistant to antibiotics. “Although people often consider UTI to be a trivial infection, there are already about a quarter of a million UTI deaths annually associated with antibiotic resistance, and this number is expected to rise,” she said.

While acknowledging the promise of the study, Rohn did point out that it contained a relatively small number of patients who self-reported their symptoms, so she feels that larger studies will be welcome. “Also, we have to keep in mind that it was performed on individuals with relatively simple recurrent UTIs, and further work is needed to understand whether it will be as effective in complicated or chronic UTI," she said.

Next Steps

Among ongoing efforts by various researchers to address the efficacy in more complex situations, Yang said that he has won funding to test the Uromune vaccine on spinal injury patients, who can experience more complicated UTIs. This will initially proceed as a small prospective trial, then be followed by a large randomised controlled trial.

Yang also pointed out that, although many other bacteria can cause UTIs in addition to the four most common ones specifically targeted by the vaccine, these other infections also seemed covered by the vaccine. “The reason for that is likely because a lot of these gram-negative bacteria share a common lipopolysaccharide outer layer… so you get a broad-spectrum response,” along with other non-targeted effects on the immune system, he suggested.

Meantime, however, the vaccine remains unlicensed in the UK, and Yang emphasised that it would be very difficult for GPs to use it off-licence, so the next steps will be to try to move forward towards regulatory approval in the UK.

“Once this treatment gets licensed it will be revolutionary for GPs,” Yang said. While emphasising that the approval will be a slow process, he feels that the emerging data, including these recent results, are steadily feeding in the evidence that will be required.