A rationally designed multi-epitope vaccine candidate targeting conserved FiuA for broad Pseudomonas aeruginosa protection

Abstract

Pseudomonas aeruginosa is a significant opportunistic pathogen, and developing a broadly protective vaccine has been hindered by its antigenic variability and immune evasion mechanisms. This study presents a rationally designed multi-epitope vaccine construct targeting the highly conserved iron acquisition protein FiuA to overcome these challenges. Our approach incorporates conserved epitope selection, epitope reciprocity (pairing B-cell epitopes with HLA class II T-cell epitopes), and optimized epitope density to maximize both cellular and humoral immune responses. We identified conserved B-cell and T-cell epitopes from FiuA and designed a construct incorporating a self-assembling peptide unit to enhance antigen presentation. In silico modeling predicts strong HLA binding affinities and broad population coverage. The resulting construct mimics pathogen-associated molecular patterns and is predicted to stimulate a robust, cross-protective immune response. This innovative strategy addresses limitations of previous P. aeruginosa vaccine efforts and offers a promising avenue for developing a broadly effective vaccine, warranting further experimental validation for its immunogenicity and protective efficacy.