Background: Fusobacterium nucleatum is a Gram-negative bacterium that is found in the human oral cavity and plays a critical role in periodontal diseases. Due to the increasing resistance to antimicrobial agents, the development of an effective vaccine against this bacterium seems inevitable. Method: In the present study, we analyzed the whole genome of F. nucleatum ATCC 25586, and only extracellular, outer membrane and secreted proteins were selected for further investigation. Next, different properties of desired vaccine targets including allergenicity, antigenicity, homology to the human proteome and gut microbiota, B-cell epitopes, MHC-II binding sites, and prevalence among 30 clinical isolates, were determined. The quartile scoring method was used to select the best immunogenic targets. The network interaction of unknown function proteins with other proteins of F. nucleatum was characterized. Finally, the interactions of all putative immunogenic targets with human TLR-2 and TLR-4 were assessed, and the immune simulation were depicted. Results: According to the obtained results, eight proteins were selected as promising immunogenic targets. These proteins were hemin receptors, complement resistance proteins, lipoproteins, cell wall-associated proteins, and unknown function proteins. The prevalence of these proteins among 30 selected clinical strains was 100%. Hemin receptors and hypothetical protein FN0465 showed the strongest binding affinity to TLR-2 and TLR-4. Besides, hypothetical protein FN0465 induced the strongest immune response. Conclusion: This study presents eight novel immunogenic targets as putative vaccine candidates against F. nucleatum. Taken together, hemin receptors and hypothetical protein FN0465 showed better immunogenic properties which worth investigating in terms of immunoreactivity and pathogenesis in the future.
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