Design and validation of a multi-epitope vaccine candidate against Acinetobacter baumannii using advanced computational methods

Abstract Acinetobacter baumannii is a significant cause of hospital-acquired infections and is often resistant to multiple antibiotics. In this study, we designed a multi-epitope vaccine candidate using the outer membrane protein K (OmpK) of A. baumannii . T-cell and B-cell epitopes were predicted, and the best epitopes were selected for multi-epitope design. For selecting the best epitopes, many in silico studies, as well as molecular docking of epitope-HLAs, were performed. The multi-epitope was designed using β-defensin as an adjuvant, PADRE sequence as an immunogenicity enhancer, and appropriate linkers. The tertiary structure of the multi-epitope was obtained using modeling and several molecular dynamics (MD)-based refinements. The sequence and/or 3D model of the multi-epitope was investigated for physicochemical, structural, in silico cloning, conformational B epitope prediction, immune response simulation, molecular docking for assay binding to toll-like receptors (TLRs), and deformability studies. The results showed that the multi-epitope construct is favorable in the case of immunogenicity, physicochemical properties, structure, binding to TLRs, solubility, stability, toxicity, allergenicity, and cross-reactivity. This multi-epitope vaccine candidate has the potential to elicit multiple immune responses against A. baumannii . However, in vitro and in vivo experimental tests are needed to validate its efficacy as a potential vaccine candidate.