Proteome-Wide Reverse Vaccinology and Immunoinformatics-Guided Design of a Multi-Epitope Vaccine Against Legionella pneumophila
Abstract
Legionella pneumophila is a Gram-negative opportunistic pathogen responsible for Legionnaires’ disease, a severe form of atypical pneumonia associated with high morbidity and mortality, particularly in immunocompromised individuals. Despite its growing global burden and the persistence of environmental reservoirs, no licensed vaccine is currently available. In this study, an integrative immunoinformatics and reverse vaccinology approach was employed to design a multi-epitope vaccine candidate targeting L. pneumophila. The complete proteome was systematically analyzed to identify essential, virulent, and surface-accessible proteins. Subsequent antigenicity assessment and non-homology screening against the human proteome led to the selection of key immunogenic targets, including KDO transferase and TolR. B-cell and T-cell epitopes were predicted and rigorously filtered based on antigenicity, non-allergenicity, and non-toxicity. Selected epitopes were assembled into a multi-epitope vaccine construct using appropriate linkers and adjuvants to enhance immunogenicity and structural stability. The designed construct exhibited favorable physicochemical properties, high antigenicity, and good solubility. Structural modeling and refinement confirmed the reliability of the predicted three-dimensional structure. Molecular docking analysis demonstrated strong binding interactions with immune receptors TLR-2 and TLR-9, which were further validated by molecular dynamics simulations…
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