A Intravesical Brucella Abortus S19 (BAS19) Vaccine As A Potential Alternative To Bacillus Calmette-Guerin (BCG) Immunotherapy: A Preclinical Study In Rats.

PURPOSE: This preliminary study aims to evaluate the immunogenicity and local immune response triggered by the intravesical administration of Brucella abortus S19 (BAS19) in a tumor-free rat model as a potential alternative to Bacillus Calmette-Guerin (BCG) in bladder cancer immunotherapy. The primary objective is to investigate immune activation and safety in the bladder, establishing a foundation for future studies assessing its therapeutic efficacy against urothelial carcinoma. MATERIALS AND METHODS: Nineteen female Wistar albino rats received intravesical BAS19 instillations and were euthanized after 3 and 6 weeks. Blood samples and cystectomy tissues were collected. The systemic immune response was assessed using the Rose Bengal agglutination test, immunocapture agglutination test, and blood cultures. Bladder tissues were examined histopathologically and stained immunohistochemically to evaluate local immune responses, specifically analyzing the expression of CD4, CD8, TLR4, and TNF-α. RESULTS: Higher Brucella-specific immunocapture titers and increased epithelial inflammation were observed in rats treated with BAS19 for 6 weeks. Moreover, significantly enhanced staining of CD4+, CD8+, and TNF-α in inflammatory cells was detected in this group. TLR4 expression was observed in all BAS19-treated rats, regardless of the exposure duration. CONCLUSION: Intravesical BAS19 administration in rats induced strong local immune responses via CD4+, CD8+, TNF-α, and TLR4 expression without systemic toxicity. These results suggest that BAS19 may mimic BCG's immunological pathways, particularly through TLR4 signaling. With its safety, low cost, and immunogenicity, BAS19 emerges as a promising immunotherapeutic candidate for further bladder cancer research.