Outer membrane vesicles of Acinetobacter baumannii: From biogenesis and pathogenesis to vaccine promise.

Outer membrane vesicles (OMVs) are nanoscale structures naturally released by Gram-negative bacteria and play important roles in host-pathogen interactions. In Acinetobacter baumannii, a critical multidrug-resistant pathogen, OMVs contribute to virulence, immune modulation, and antibiotic resistance, while also representing promising vaccine candidates. In this review, we summarize current advances in the biogenesis, pathogenic functions, and vaccine applications of A. baumannii OMVs. We discuss the major mechanisms proposed for OMV biogenesis, factors regulating OMV production, and the diverse roles of OMVs in biofilm formation, resistance dissemination, and host immune responses. We further evaluate recent progress in native, detoxified, and engineered OMV-based vaccine platforms, with particular emphasis on endotoxin detoxification, antigen selection, and strategies for improving OMV yield and immunogenicity. We also compare the current status of A. baumannii OMV vaccines with the successful clinical development of meningococcal OMV vaccines and highlight the major challenges that remain for clinical translation. Collectively, this review provides an updated perspective on the opportunities and limitations of OMV-based interventions and outlines future directions for the development of safe, standardized, and broadly protective vaccines against A. baumannii.