Pangenomics-Driven Reverse Vaccinology for the Discovery of New Vaccine Candidates Against Bordetella pertussis

Despite widespread vaccination, pertussis resurgence persists due to waning immunity and emerging resistant strains in Bordetella pertussis . This study employs a pangenomics-driven reverse vaccinology approach to identify novel vaccine candidates. Analyzing 160 genomes revealed a closed pan-genome, with approximately 60% conserved genes, including 3389 core genes of which 1312 participate in pathogen-specific pathways. Non-homologous proteins were identified by comparison against human and microbiome proteomes, yielding 205 candidates. Essentiality assessment via the Database of Essential Genes (DEG) refined this to 63 non-homologous essential proteins. A multi-criteria selection process evaluated purifiability based on physicochemical properties and transmembrane helices, accessibility (extracellular or secreted localization), and immunogenicity through antigenicity prediction and B-cell epitope mapping. This pipeline culminated in 11 high-potential vaccine targets. The in silico methodology offers rapidity, cost-effectiveness, and reduced side effects compared with conventional vaccinology, though experimental validation is essential for confirmation.