The main objective of this study was to analyze the efficacy of Uromune® vaccine to prevent uncomplicated recurrent UTI and perform a follow-up protocol.

This is a prospective, descriptive, and multicenter research. 
From January 2011 to May 2023, 1104 women with 3 or more urinary tract infections in the 12 months prior to the first visit were included. All patients received immunoprophylaxis with Uromune® sublingual vaccine, with a frequency of two puffs every 24h while fasting over along 3 months. Each puff was equivalent to 109 of whole bacteria inactivated by heat in each milliliter, with the same percentage for each of the 4 most frequent UTI-causing bacteria in Spain: Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, and Enterococcus faecalis (1). In cases of therapy with autovaccine, each pulse contained 100% of the bacteria isolated in the urine culture from the sample provided by the patient to the pharmacy office to manufacture the vaccine, and in case of growth of 2 bacteria, 50% of each (2).
Anamnesis and urine culture were performed at 3, 6, and 12 months after the end of treatment. 
UTI was defined as the presence of 100.000 or more germs colony-forming units that colonize and multiply in the urinary system with symptoms (3).
The efficacy of Uromune® was defined as the presence along follow-up of 0, 1, or 2 UTI positive urine cultures after the end of treatment.
Variables analyzed were age, bacteria, number of UTIs at baseline and at 3, 6, and 12 months of follow-up, distribution according to groups of age and months of the year, and therapy with vaccine or autovaccine. 
Statistical analysis was performed with SPSS version 15.0. To compare proportions Chi-square test was used, with Fisher modification when necessary. Comparatives between quantitative variables were performed with Student’s t- test.
Exclusion criteria of the study were patients diagnosed of neuro-genic bladder, symptomatic urinary calculi, patients with nephrostomy, ureteral pigtail and urethral catheter, presence of moderate to severe urinary incontinence defined as the presence of three or more one-hour pad tests equal to or greater than 50 cc along 24 h, patients with lower urinary tract symptoms (LUTS) in progression defined as patients with IPSS greater than 20 despite medical treatment with alpha blockers, 5-alpha-reductase inhibitors or both combined, LUTS and cystocele with postvoid volume greater than 100 ml, and patients with urinary diversion.
Patients were divided into two groups according to the number of UTI at baseline. Group 1 had 3 or 4 UTI, and Group 2 had patients with 5 or more UTI. We compared the results after vaccination between both groups and performed a follow-up protocol.
All patients received oral and written information about Uromune®, and written informed consent was recorded.

The median age was 72 years and the bacteria isolated were Escherichia coli with 64,3%, Klebsiella pneumoniae with 24,3%, Proteus vulgaris with 5,9%, Enterococcus faecalis with 3,5%, Pseudomona aeruginosa with 1,4% and Citrobacter koseri with 0,5%.
The distribution by month of the year of consultations for UTI at baseline was January 6,8%, February 11,3%, March 12,3%, April 11%, May 8,6%, June 5,3%, July 7,4%, August 4,8%, September 7,2%, October 10,1%, November 8,1% and December 7,1%.
According to age at baseline, patients were divided under 30 years old, 30 to 50, 50 to 70 and over 70 years old. The distribution by age was under 30 years old 1.9%, from 30 to 50 5.4%, from 50 to 70 26.5% and over 50 years old 66. 1%.
Autovaccine was administered to 456 patients, 41,3%, and 648 received polyvalent vaccine, 58,7%.
Side effects with Uromune® were mild and represented 1.36%. No patient abandoned treatment. 8 presented dry mouth, 4 gastritis and 3 sickness. No side effects were observed in patients treated with autovaccines.
The number of UTI at baseline was 3 UTI 40,8%, 4 UTI 24,5%, 5 UTI 19%, 6 UTI 9,8%, 7 UTI 4,1%, 8 UTI 1,6%, 9 UTI 0,2% and 10 UTI 0,1%.
Follow-up was registered in 100% of sample at 3 and 6 months, but at 12 months only 55%, 611 patients.
Three months after immunoprophylaxis, 41,5% had 0 UTI, 30,5% 1 UTI, 19,7% 2 UTI, 6,7% 3 UTI, 1,4% 4 UTI, 0,1% 5 UTI and 0,1% 6 UTI. Efficacy at 3 months was 91,7%.
At 6-month follow-up, 26% had 0 UTI, 32,5% 1 UTI, 23,8% 2 UTI, 12,9% 3 UTI, 3,9% 4 UTI, 0,5% 5 UTI, 0,3% 6 UTI and 0,1% 7 UTI. Efficacy at 6 months was 82,3%.
At 12-month follow-up, 9,8% had 0 UTI, 27,5% 1 UTI, 20,3% 2 UTI, 25,5% 3 UTI, 13,6% 4 UTI, 2,6% 5 UTI, 0.5% 6 UTI and 0,2% 7 UTI. Efficacy at 12 months was 57,6%.
At 3, 6 and 12 months follow-up patients with vaccines had an efficacy of 95,8%, 88,4% and 56,1%, and autovaccines had 85,7%, 73,6% and 60,2% respectively. The study between vaccines and autovaccines was statistically significant to vaccines at 3, 6 and 12 months (p<0,05). 
Group 1 represented 65,2% of the sample, 720 patients, and Group 2 was 34,8%, 384 patients. In Group 1 the efficacy was 97,7%, 91,9% and 64,7% at 3, 6 and 12 months respectively. In Group 2 the efficacy was 88,2%, 64,3% and 40% at 3, 6 and 12 months. The analysis between both groups was statistically significant to Group 1 (p<0.05) (Table 1).

Uromune® showed that patients who initially have less than 5 UTI will have better result than the others, and that is the reason to propose a new protocol in the inmunoactive prophylaxis of uncomplicated recurrent UTIs (Figure 1).
Patients with less than 5 UTI at baseline will receive 1st round of vaccine. Result: if 0-2 UTI, clinical follow-up and urine culture at 6 months will be the best option. If 3 or more UTI were presented without symptoms, follow-up at 6 months will be mandatory, and if patients had 3 or more UTI with symptoms 2nd round of re-vaccinate will be necessary.
Patients with 5 or more UTI at baseline will follow 2 rounds of vaccine initially. Result: if 0-2 UTI and absence of symptoms, clinical follow-up with urine culture at 6 months will be the best option. If 0-2 UTI with symptoms of UTI, patients had to re-vaccinate on 3rd round. Result: if 3 or more UTI after second round, re-vaccinate (3rd round).

Inmunoactive prophylaxis with Uromune® offers high efficacy in patients with uncomplicated recurrent UTI.
The follow-up protocol with Uromune®, according to the number of UTI at baseline, the result of urine culture along follow-up and the presence or not of symptoms, can be very useful to improve the quality of life of our patients.
Whenever available, polyvalent vaccines are recommended because can offer better results than autovaccines.

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