Development of Multi-epitope Subunit Vaccine Against Pseudomonas aeruginosa Using OprF/OprI and PopB Proteins

Abstract

Background: The emerging problem of antibiotic resistance in Pseudomonas aeruginosa is a global health concern; hence, revealing innovative therapeutic approaches (such as designing an immunogenic vaccine candidate) is needed. There is no evidence of the availability of an effective vaccine that can combat the infection caused by this microorganism. Objectives: This research was conducted to develop a potential chimeric vaccine against P. aeruginosa using reverse vaccinology approaches. Methods: The present vaccine candidate comprised outer membrane protein F and I (OprF/OprI) and PopB with appropriate linkers. After applying meticulous immune-informatics investigation, the multi-epitope vaccine was created, including helper T lymphocyte (HTL), cytotoxic T lymphocyte (CTL), interferon gamma (IFN-γ), and interleukin 4 (IL-4) epitopes. Then, the physicochemical characteristics, allergenicity, toxicity, and antigenicity were analyzed. After investigating the secondary structure, the tertiary structure (3D) model was generated, refined, and validated via computational methods. Besides, the strong protein-ligand interaction and stability between the vaccine candidate and toll-like receptor 4 (TLR4) were determined via molecular docking and dynamics analyses. Moreover, in silico cloning accompanied by pET-22b (+) was used to achieve high translation efficiency. Results: Our results presumed that the chimeric-designed vaccine was thermostable and contained optimal physicochemical properties. This vaccine candidate was nontoxic and highly soluble and had stable protein and TLR4 interaction, adequately overexpressed in Escherichia coli. Overall, it could induce immune responses and repress this microorganism. Conclusions: Therefore, to inhibit Pseudomonas infections experimentally, the efficacy and safety of the vaccine design need to be validated.

The Promising Potential of Reverse Vaccinology-Based Next-Generation Vaccine Development over Conventional Vaccines against Antibiotic-Resistant Bacteria

“…It was also nontoxic and highly soluble. Overall, it might stimulate the immune system and suppress P. aeruginosa [208]. Dey et al (2022) demonstrated that the primary membrane protein candidate of P. aeruginosa was a crucial factor in the susceptibility of the bacteria to antimicrobial peptides and its ability to survive inside hosts [209].…”

“…Reverse vaccinology techniques were employed in an experimental study to develop a potent chimeric vaccine against P. aeruginosa [ 208 ]. The vaccine candidate included PopB and outer membrane protein F and I (OprF/OprI) joined together using linkers.…”

“…It was also nontoxic and highly soluble. Overall, it might stimulate the immune system and suppress P. aeruginosa [ 208 ].…”