Design of a Multi-Epitope Vaccine Against Pseudomonas aeruginosa Using an Immunoinformatics Approach

Pseudomonas aeruginosa is a high-priority pathogen identified by the WHO. With the slow development of new antibiotics, alternative approaches are essential. This study aims to design a multi-epitope vaccine to prevent P. aeruginosa infections using reverse vaccinology and immunoinformatics. We screened the entire proteome of P. aeruginosa (5,563 proteins) for non-homology with the human proteome, stability, non-allergenicity, adhesion, and immunogenicity. The signal peptide-containing proteins like Probable Coat Protein A of bacteriophage Pf1, Alkaline Phosphatase L, and a Secreted Protein were identified as suitable vaccine targets. These targets underwent physicochemical analysis followed by prediction of B-cell, CTL, and HTL epitopes. Only antigenic, non-allergenic, and non-toxic epitopes were selected for molecular docking with human TLR2 and TLR4 receptors. We designed six vaccine candidates (DV1 - DV6) incorporating various adjuvants. The designed constructs were evaluated for physicochemical properties, and 3D structures were validated with a Ramachandran plot. Further molecular dynamics simulations indicated that DV5, containing HBHA conserved peptide sequence as an adjuvant, exhibited promising stable binding affinities with TLR2 and TLR4. The population coverage of DV5 was found to be 98.28% worldwide. Finally, the In-silico cloning was carried out to check the expression feasibility of the vaccine construct. In conclusion, this multi-epitope vaccine could be a potential candidate against P. aeruginosa infections, necessitating further research to confirm its safety and efficacy.