{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T17:46:43Z","timestamp":1787161603228,"version":"build-2736575974"},"reference-count":35,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T00:00:00Z","timestamp":1715212800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Introduction: A subset of interstitial cystitis\/bladder pain syndrome (IC\/BPS) patients experience recurrent urinary tract infection (rUTI) associated with symptom flares. Recurrent UTI subjects with associated IC\/BPS were enrolled in the first North American early clinical experience trial evaluating a new sublingual UTI preventative vaccine, MV140. It has been shown that women with rUTI develop an imbalance in the T helper 1 and 2 (Th2 over-expression) in the bladder mucosa. Our hypothesis-generating secondary analysis will suggest that this infection subcategory of IC\/BPS patients develop a similar imbalance of Th1-Th2 response type to bacteria present in their urinary microbiome, leading to a bladder hypersensitivity that responds to mucosal immune modulation. Methods: Female participants with \u22653 documented UTI\/year underwent a 3-month vaccination treatment period with a 9-month efficacy period after completion of vaccine treatment (total 12 months). There were no exclusion criteria for subjects in relation to baseline urinary symptoms and\/or discomfort\/pain. Primary outcome was no UTI following vaccination. Secondary outcomes included change in UTI incidence, overall patient-reported subjective global assessment (SGA responder defined as moderately or markedly improved on 7-point scale), and safety. Results: Sixteen subjects with IC\/BPS-related symptoms and rUTI (mean age 47; range 23\u201374 years; mean number of UTI episodes in previous year 6.1 +\/\u2212 4.2) were eligible to be included in the Health Canada-approved MV140 vaccine study for prevention of rUTI. All subjects completed the 3-month vaccination period. One subject was lost to follow-up after their 6-month visit. Six subjects were UTI-free, while all 16 subjects had a reduction in UTI episodes compared to the year pre-vaccination. The total post-vaccination reduction in UTI episodes compared to pre-vaccination was 80% (0.1 UTI\/subject\/month from 0.5 UTI\/subject\/month, respectively). At 12 months, 13 subjects (81%) were SGA responders (moderately or markedly improved), and the responders reported a reduction in IC\/BPS symptoms, with 8 subjects reporting significant or almost complete resolution of their specific long-term bladder discomfort\/pain and bothersome urinary frequency or urgency. Four subjects reported mild and self-limited adverse events during vaccination period, but none were related to MV140 vaccine. Conclusion: Sublingual MV140 vaccine in IC\/BPS patients with rUTI not only achieved UTI-free or reduced UTI incidence status but also, after approximately 9 months post vaccination, resolution of patients\u2019 long-term treatment-refractory IC\/BPS symptoms. This suggests some cases of IC\/BPS may be etiologically based on Th2-driven hypersensitivity to bacteria within or entering the urinary microbiome that responds to a vaccine whose mechanism of action is to normalize or balance the bladder Th1\/Th2 mucosal immune system.<\/jats:p>","DOI":"10.3390\/pathogens13050396","type":"journal-article","created":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T03:34:19Z","timestamp":1715225659000},"page":"396","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Secondary Analysis of Interstitial Cystitis\/Bladder Pain Syndrome Patients Enrolled in a Recurrent Urinary Tract Infection Prevention Study Provides a Novel Paradigm for Etio-Pathogenesis and Practical Management of This Infection Phenotype"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4865-7293","authenticated-orcid":false,"given":"J. Curtis","family":"Nickel","sequence":"first","affiliation":[{"name":"Department of Urology, Queen\u2019s University, Kingston, ON K7L2V7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6762-3649","authenticated-orcid":false,"given":"Tiziana","family":"Cotechini","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences, Queen\u2019s University, Kingston, ON K7L3N6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Christopher","family":"Doiron","sequence":"additional","affiliation":[{"name":"Department of Urology, Queen\u2019s University, Kingston, ON K7L2V7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"99","DOI":"10.5213\/inj.2142084.042","article-title":"Current Understanding and Future Perspectives of Interstitial Cystitis\/Bladder Pain Syndrome","volume":"25","author":"Ueda","year":"2021","journal-title":"Int. Neurourol, J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"E136","DOI":"10.5489\/cuaj.3786","article-title":"CUA guideline: Diagnosis and treatment of interstitial cystitis\/bladder pain syndrome","volume":"10","author":"Cox","year":"2016","journal-title":"Can. Urol. Assoc. 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