At the AUA 2021 meeting late last year, Dr. Curtis Nickel presented the latest research for a novel sublingual vaccine for the prevention of urinary tract infections in women. Uromune (MV140) is a simple, sublingual vaccine that could ease the suffering of millions of women. It is currently in the phase 3 development “pre-licensing” trials in 26 countries world wide, including the UK, New Zealand, Germany, Spain, Belgium, Czechia, Denmark, Finland, France, Luxembourg, Netherlands, Norway, Romania, Serbia, Slovakia, Slovenia, Sweden and Turkey.

UTI’s Can Be Difficult To Treat

Approximately 60% of women will experience an acute bladder infection in their lifetime.(1) Of these, 20-40% are likely to experience additional infections. 25% to 50% of these women will experience recurring UTI’s (two infections in six months or three or more infections per year), costing billions of dollars annually across the world.(2,3,4) Recurring UTI’s can take a devastating toll on the patients who seeking treatment for an infections that are often antibiotic resistent.

Treatment is difficult. The American Urology Association Guidelines for UTI focus on the use of antibiotics which can result in significant and serious side effects with poor long-term effectiveness.(5) As millions of women can attest, infections often recur after antibiotics are discontinued.

Uromune UTI Vaccine Sprayed In Mouth

Uromune is a self-administered submucosal vaccine that is sprayed under tongue, once daily for three months. It is composed of “whole cell, heat inactivated bacteria, including equal amounts of four common UTI pathogens:  Escherichia coli; Klebsiella pneumoniae; Proteus vulgaris; and Enterococcus faecalis (MV140 formulation). Studies have shown that it causes innate and adaptive immunity, including in the genitourinary tract.(6)

Five European studies looked at Uromune for the prevention of recurrent urinary tract infections. Over 1,400 women experiencedurinary tract infection-free rates ranging from 33% to 90%. Two studies which compared the vaccine to prophylactic antibiotics, found a superior clinical benefit to the vaccine with less than 2% adverse reactions.

Over 40,000 Patients Treated With Excellent Safety Profile

Over 40,000 patients outside North America have received this vaccine in special access programs. Since 2017, safety data for almost 21,000 individuals, representing 1.5 million doses has been collectively with only eight safety case reports. Most adverse events were mild and self-limited (i.e. dry mouth and gastritis)  leaving the researchers to believe that this is a very safe vaccine.

Based in Kingston Ontario, Dr. Nickel said “We have the only North American early clinical experience. We have 67 female subjects to date, vaccinated, and data on the pre-COVID cohort. Those are the ones that were vaccinated before the temporary COVID mandatory clinical trial shutdown in our institution. In that cohort, the UTI-free rate, that is no urinary tract infection after vaccination, was almost 50%, with an overall reduction in UTIs of 82%, and only two mild and self-limited vaccine-related adverse reports, in one of these patients.”

The only way to prove whether or not a vaccine is effective is with a randomized placebo-controlled trial. Dr. Nickel presented the pivotal, randomized placebo-controlled trial, in which subjects were randomized to either placebo for six months, a vaccine for three months, followed by three months of placebo, or a vaccine for six months, with six months further follow-up. The efficacy period started at three months after the intervention, either placebo or the vaccine.

Recurring UTI Patients Had Fewer Symptoms With Uromune

In women with recurrent UTI, this vaccine significantly reduced the risk of UTI, from a median UTI rate in the placebo group of three over the nine months, to zero, a median in both the three and six-month groups. The UTI-free rate, in these patients who had on average, or median, six UTIs per year, prior to vaccination, the UTI-free rate was around 55% to 58%. He said “If patients did suffer a UTI, those in the vaccinated group had significantly fewer symptoms and more self-limited disease.”

The time to UTI was only 48 days in the placebo group, compared to 275 days for a median time to UTI rate in the treated group.The vaccine decreased the overall need for the use of antibiotics, healthcare resources, and costs associated with recurrent urinary tract infection management. He continued “It was extremely safe, with very few adverse events related to the vaccine. And only three patients in the entire study stopped the intervention. One of them was in the placebo group, due to an adverse event.”

This early data presents a compelling case for vaccination which, based upon several studies, appears to be more effective than antibiotic prophylaxis. It would reduce overall antibiotic use in this large population of patients thereby decreasing the risk of antibiotic resistance. Dr Nickel concluded “There is no doubt in my mind that this vaccine will be a game-changer in the management of recurrent urinary tract infections in women.”

Uromune is not the only vaccine in development. Researchers at Duke University and the University of Colorado recently shared their novel approach, the introduction of a vaccine containing E.coli directly into the bladder. No human studies, as yet, have been conducted with this approach though mouse studies appear promising.(7)

Uromune is not currently available in the USA though Canadians can participate via the clinical trial currently being conducted by Dr. Nickel at Queens University.

Current Uromune Clinical Trial Listings

References:

  1. Foxman B: Urinary tract infection syndromes: occurrence, recurrence, bacteriology, risk factors, and disease burden. Infect Dis Clin North Am 2014; 28: 1.
  2. Geerlings SE: Clinical presentations and epidemiology of urinary tract infections. Microbiol Spectr 2016; 4.
  3. Gupta K, Trautner BW: Diagnosis and management of recurrent urinary tract infections in non-pregnant women. BMJ 2013; 346: f3140.
  4. Foxman B: Epidemiology of urinary tract infections: incidence, morbidity, and economic costs. Am J Med 2002; 113: 5S.
  5. Anger, et al. Recurrent Uncomplicated Urinary Tract Infections In Women: AUA/CUA/SUFU Guideline 2019. J Urol. 2019 Aug; 202(2):282-289.
  6. Nickel, et al. Could sublingual vaccination be a viable option for the prevention of recurrent urinary tract infection in Canada? A systematic review of the current literature and plans for the future. Can Urol Assoc J. 2020 Aug; 14(8): 281–287.
  7. Wu, et al. Local induction of bladder Th1 responses to combat urinary tract infections. Proceedings of the National Academy of Sciences of the USA. PNAS March 2021