A review of the literature shows the sublingual vaccine holds promise for the treatment of this condition.
MV140 (Uromune; Red Leaf Medical) is a novel sublingual mucosal-based bacterial vaccine that could fulfill an unmet need for women with uncomplicated recurrent urinary tract infections (rUTIs). rUTI is defined as 2 episodes of acute bacterial cystitis within 6 months or 3 episodes within 1 year.1 A total of 11% of women develop a UTI each year, with more than 25% reporting a second UTI within 6 months, resulting in a reported rUTI yearly incidence rate in women of 3%.2
Image credit: Vitalii Vodolazskyi | stock.adobe.com
Currently, treatment for rUTI is prophylactic antibiotics to decrease the risk of future UTIs. The most common antibiotics prescribed are sulfamethoxazole/trimethoprim, nitrofurantoin, cephalexin, and fosfomycin.1 Antibiotics are not an inert substance when used long term; they carry serious adverse effect risks and can contribute to antibiotic resistance. The European Association of Urology Urological Infections Guidelines discusses immunoactive prophylaxis strategies for rUTI, including MV140, OM-89, and StroVac.3 None of these products are currently FDA approved in the United States. The 2022 American Urological Association (AUA) guideline for rUTIs in women does not endorse any product specifically, but it does note that novel technologies, such as vaccines for urinary pathogens, may be the future for prevention of rUTI.1
MV140 is a polyvalent, bacterial, whole cell–based, sublingual vaccine that is currently available under special access programs.2 It is also approved in 26 countries, including Spain, Portugal, the United Kingdom, and Mexico.4 MV140 is administered by the patient in a dose of 2 sublingual sprays daily for 3 months. The novel vaccine contains 4 strains of bacteria, including Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis, and Proteus vulgaris. The sublingual spray is formulated with pineapple flavoring2; the sublingual route of vaccine administration has been shown to avoid degradation by gastric fluids and gastrointestinal enzymes, which allows lymphocytes and other immune cells from the sublingual mucosa to migrate to the bladder mucosa. MV140 induces immune responses both systemically and locally at the genitourinary tract.5
Evidence for the safety and efficacy of the vaccine has been building over the years. A 2013 multicenter observational study compared 159 women treated with MV140 for 3 months with 160 women treated with sulfamethoxazole/trimethoprim 200/40 mg/day for 6 months. A clinically significant difference was seen at 3-, 9-, and 15-month follow-up periods. The numbers of patients who did not have any UTI at 3, 9, and 15 months were 101, 90, and 55, respectively, in the MV140 group vs 9, 4, and 0, respectively, in the antibiotic group.6 These results show that all women in the antibiotic group reported a UTI at the 15-month follow-up point, whereas 55 of the 159 women in the MV140 group reported being UTI free at the 15-month follow-up point. Based on this study, MV140 was worthy of further investigation.
In 2015, a larger retrospective cohort study (NCT02543827) evaluated a total of 669 women with rUTI. This study population included approximately double the number of women from the previous 2013 study. This time, women either received a 6-month rUTI prophylaxis with antibiotics (nitrofurantoin or sulfamethoxazole/trimethoprim) or a 3-month rUTI prophylaxis with MV140. The primary outcome was the time frame after the prophylaxis period until the first infection within 1 year. All patients treated with antibiotics had a new UTI during the 1-year follow-up period compared with only 35 patients (9.7%) in the MV140 group. There were no reported adverse effects with the use of MV140 in this study.7 Once again, MV140 demonstrated ongoing promise for women with rUTIs at both a safety and efficacy level.
Clinical trials on MV140 began moving from retrospective studies to prospective studies. In 2018, a small prospective observational study in the United Kingdom was conducted with a total of 77 women with rUTIs. These women were treated with MV140 for 3 months and were observed during a follow-up period of 12 months. A total of 75 women completed the treatment and 78% of them had no subsequent UTIs during the 12-month follow-up time period. The 2 women who did not complete the study stopped for 2 different reasons: One patient experienced an allergic reaction and discontinued MV140, whereas the other stopped for lifestyle and personal reasons, including not liking the taste of the spray and nonadherence with fasting before and after the vaccine for 2 hours.8 Although the study population was small, this prospective study demonstrated that MV140 had efficacy at preventing UTIs and was well tolerated in women with rUTIs.
A 2019 prospective study in a larger patient population (784 patients), data from which were published, included both men and women with rUTIs. In this study, 82.7% of participants were women. In the same fashion as the other studies, the patients were treated with daily MV140 for 3 months. At 3 months post therapy, 71.7% of patients had 0 or 1 episode of UTI. At 6 months post therapy, 64.7% of patients had 0 or 1 episode of UTI.9 This large prospective study demonstrated positive results for MV140 in a broader patient population than previous studies that were limited to only women with rUTIs.
Most recently in 2024, the results of the first North American clinical experience study with MV140 were published. This study was smaller than the 2018 and 2019 studies and included only 67 participants. Prior to vaccination, patients reported an average of 6.8 UTIs per year. The UTI-free rate for the 9-month post-vaccination period was 40.6%. When compared with the UTI rate in the year prior to the vaccination, there was a 75.9% reduction for the 9-month efficacy period. Adverse effects related to the vaccine were seen in 14 patients; these included skin rash/sensitivity, mucosal burning/sensitivity, upper gastrointestinal discomfort, and fatigue. All were mild and resolved within 3 months.2 Once again, the evidence shows promising results in favor of MV140.
Currently, randomized controlled trials are lacking for MV140, which would be the ideal level of evidence to support treatment efficacy and minimize confounders. Per ClinicalTrials.gov, there is a recently completed phase 2 clinical trial (NCT04096820) conducted in Canada that is still pending the publication of results. However, there are currently no clinical trials with MV140 ongoing in the United States.10
Christina Bookwalter, PharmD, MS, MEd, BCPS, BCACP, is a clinical pharmacist practitioner at a Minneapolis, Minnesota, health care system and adjunct faculty at Wilkes University Nesbitt School of Pharmacy in Wilkes-Barre, Pennsylvania.
Overall, the body of evidence demonstrates that MV140 holds promise for women with rUTIs. As the 2022 AUA guidelines predicted, novel technologies such as vaccines for urinary pathogens may be the future for rUTI prevention. Further research will determine the future novel prevention strategies that could become the standard of care for patients with rUTIs. Approval for a novel treatment could reduce the reliance on prophylactic antibiotics, mitigate the risk of antibiotic resistance, and improve long-term patient outcomes.
