Objectives: The emerging multidrug-resistant strains of Acinetobacter baumannii and the limited available treatment options, have led the World Health Organization to enlist this pathogen among the microorganisms with critical priority demanding the development of novel treatment alternatives. This study aimed at exploring, for the first time, the potential of an efflux-related protein, the ATP-binding cassette (ABC) transporter substrate-binding protein, as a vaccine candidate against A. baumannii infections. The ABC transporter substrate-binding protein is known to play a role in the iron acquisition pathway of A. baumannii. It utilizes the energy released from the hydrolysis of ATP in the transportation of the iron-bound siderophore across the plasma membrane into the cell.  Methods: In this work, the ABC transporter substrate-binding protein was expressed in Escherichia coli after cloning its respective gene into pQE31 plasmid vector. The protein was purified using metal affinity chromatography. The purified antigen was administered to mice in combination with Bacillus Calmette–Guérin (BCG) and alum nanoparticles as adjuvants. Immunological parameters were assessed, and protection was tested following bacterial challenge in a murine infection model. Results: Two weeks after the last immunization dose, serum samples were tested for antigen-specific IgG antibody response which was extremely significant in immunized mice when compared with negative control mice. Following challenge of mice with A. baumannii, only a short-lived protection lasting for 24 hours was obtained. Conclusion:  The diversity of the virulence factors exhibited by A. baumannii including several iron acquisition mechanisms might necessitate the design of a multi-component vaccine to elicit effective protection. Furthermore, the immunization regimen, the used adjuvant, and the route of administration are critical factors which are worthy of further investigation to fulfill complete long-lasting protection.
te of administration are critical factors which are worthy of further investigation to fulfill complete long-lasting protection.