In silico design and assessment of a multi-epitope peptide vaccine against multidrug-resistant Acinetobacter baumannii

In Silico Pharmacol. 2024 Dec 24;13(1):7. doi: 10.1007/s40203-024-00292-3. eCollection 2025.

Abstract

Acinetobacter baumannii, an opportunistic and notorious nosocomial pathogen, is responsible for many infections affecting soft tissues, skin, lungs, bloodstream, and urinary tract, accounting for more than 722,000 cases annually. Despite the numerous advancements in therapeutic options, no approved vaccine is currently available for this particular bacterium. Consequently, this study focused on creating a rational vaccine design using bioinformatics tools. Three outer membrane proteins with immunogenic potential and properties of good vaccine candidates were used to select epitopes based on good antigenic properties, non-allergenicity, high binding scores, and a low IC50 value. A multi-epitope peptide (MEP) construct was created by sequentially linking the epitopes using suitable linkers. ClusPro 2.0 and C-ImmSim web servers were used for docking analysis with TLR2/TLR4 and immune response respectively. The Ramachandran plot showed an accurate model of the MEP with 100% residue in the most favored and allowed regions. The construct was highly antigenic, stable, non-allergenic, non-toxic, and soluble, and showed maximum population coverage. Additionally, molecular docking demonstrated strong binding between the designed MEP vaccine and TLR2/TLR4. In silico immunological simulations showed significant increases in T-cell and B-cell populations. Finally, codon optimization and in silico cloning were conducted using the pET-28a (+) plasmid vector to evaluate the efficiency of the expression of vaccine peptide in the host organism (Escherichia coli). This designed MEP vaccine would support and accelerate the laboratory work to develop a potent vaccine targeting MDR Acinetobacter baumannii.

Supplementary information: The online version contains supplementary material available at 10.1007/s40203-024-00292-3.

Keywords: Acinetobacter baumannii; Immune-simulation; In silico; Molecular docking; Multi-epitope peptide; Vaccine.