Immunoinformatics Approach to Designing a Subunit Vaccine Construct of Pseudomonas aeruginosa Outer Membrane Epitopes

Introduction: Antibiotic-resistant Pseudomonas aeruginosa has been designated by the World Health Organization (WHO) as a critical priority pathogen, highlighting the critical need for developing new strategies, particularly prophylactic measures. This research focuses on incorporating highly antigenic elements from essential, surface-exposed outer membrane proteins of P. aeruginosa to design a polypeptide-based subunit vaccine capable of inducing a strong immune response, using immunoinformatics approaches. Methods: Ten essential outer membrane proteins of P. aeruginosa were analyzed using three online servers (ABCpred, BCPREDS, and LBtope) to predict B-cell epitopes and the IEDB server to predict CD8+ and CD4+ T-cell epitopes. The predicted epitopes were then assessed for physicochemical properties, allergenicity, and toxicity using relevant web servers. A vaccine construct incorporating the selected epitopes and an adjuvant was designed, and its 3D structure was modeled to study its interaction with Toll-like receptor-4 (TLR-4). Results: The final vaccine construct consisted of a 478-amino acid polypeptide incorporating 5 CD8+ T-cell, 5 CD4+ T-cell, and 15 B-cell epitopes. In silico analysis predicted the vaccine construct to be immunogenic, non-toxic, non-allergenic, and possess favorable physicochemical properties. Molecular docking simulations predicted strong binding affinity between the vaccine construct and TLR-4, suggesting its potential to elicit a robust immune response. Conclusion: These in silico analyses suggest that the designed subunit vaccine is potentially safe and effective against P. aeruginosa. However, experimental validation is necessary to confirm these predictions.