biostudies-literatureGong YPediatric Precision Surgical Clinical Medical Center of SuzhouSuzhou Program of Gusu Medical TalentNational Natural Science Foundation of ChinaNatural Science Foundation of Jiangsu Provincee04101https://www.ebi.ac.uk/biostudies/studies/S-EPMC12499445biostudies-literatureUnknown12(37)Trained immunity, an innate immune memory, has emerged as a promising strategy to enhance host defense against sepsis, a leading cause of mortality in critical care. While Bacillus Calmette-Guérin (BCG) is the most widely used vaccine for tuberculosis prevention, its broader use as an inducer of trained immunity is limited by adverse reactions. Here, it is reported that BCG-derived outer membrane vesicles (B-OMVs) effectively trigger trained immunity to protect against experimental polymicrobial sepsis. Comprehensive characterization and safety assessments confirmed that B-OMVs exhibited no significant toxicity or pathological effects, positioning them as a promising alternative to conventional BCG vaccines and E. coli-derived outer membrane vesicles (E-OMVs) in terms of both efficacy and Advanced science (Weinheim, Baden-Wurttemberg, Germany)BCG-Derived Outer Membrane Vesicles Induce TLR2-Dependent Trained Immunity to Protect Against Polymicrobial Sepsis.PMC12499445BE20237148237218382272215BE202371382172132GSWS2020043Szzxj201505Xu LKang RHuang JYang KDong ZHao WBai ZTang DGong YJin ZWang JZhou ZYang YPan PShan QWang JHZhou HfalseBCG-Derived Outer Membrane Vesicles Induce TLR2-Dependent Trained Immunity to Protect Against Polymicrobial Sepsis.Trained immunity, an innate immune memory, has emerged as a promising strategy to enhance host defense against sepsis, a leading cause of mortality in critical care. While Bacillus Calmette-Guérin (BCG) is the most widely used vaccine for tuberculosis prevention, its broader use as an inducer of trained immunity is limited by adverse reactions. Here, it is reported that BCG-derived outer membrane vesicles (B-OMVs) effectively trigger trained immunity to protect against experimental polymicrobial sepsis. Comprehensive characterization and safety assessments confirmed that B-OMVs exhibited no significant toxicity or pathological effects, positioning them as a promising alternative to conventional BCG vaccines and E. coli-derived outer membrane vesicles (E-OMVs) in terms of both efficacy and 2025-01-01T00:00:00Z2025 Oct2026-06-04T04:46:58.646Z2026-05-05T03:12:37.454ZS-EPMC124994454055237510.1002/advs.202504101