LAUSR

The development of vaccines represents a promising and safe strategy to combat multidrug‐resistant (MDR) Acinetobacter baumannii (A. baumannii) infections. In this study, we designed and evaluated a dendritic cell (DC)‐targeting multiepitope peptide‐based biomimetic nanovaccine for its immunogenicity and protective efficacy in a murine model. Bioinformatics tools were employed to predict and screen B‐ and T‐cell epitopes derived from the OmpW protein of A. baumannii, followed by immunological validation. The dominant epitopes were sequentially linked using 6‐aminocaproic acid to synthesize a multiepitope peptide, rOmpW. Subsequently, rOmpW was encapsulated within polylactic‐co‐glycolic acid (PLGA) nanoparticles coated with neutrophil membranes (NM), and the surface was functionalized with a DC‐targeting peptide (DCpep) to construct the biomimetic nanovaccine, DCpep‐NM‐PLGA‐rOmpW. This biomimetic nanovaccine elicited robust Th1 and Th17 cellular immune responses, as well as humoral immunity, and demonstrated significant protective efficacy in a murine model of acute lethal pneumonia caused by A. baumannii. These findings underscore the translational potential of this biomimetic nanovaccine as a prophylactic strategy against A. baumannii infections.