Targeting Pathogenic <i>Desulfovibrio</i> Species with a Novel Multi-Epitope Vaccine: A Reverse Vaccinology and Computational Approach

Disulfovibrio (DSV) blooms are linked to gastrointestinal and systemic diseases due to their production of hydrogen sulfide, lipopolysaccharides (LPS), extracellular vesicles and mucolytic activity. Despite their health implications, targeted therapies are lacking. This novel study introduces a multi-epitope vaccine candidate (MVC) as an innovative therapeutic solution for DSV-linked diseases. Herein, immunoinformatics and computational techniques were combined to design an MVC targeting four key pathogenic strains of DSV: D. desulfuricans, D. fairfieldensis, D. piger and D. vulgaris implicated in inflammatory bowel disease, cancer, neurodegeneration, metabolic syndromes, periodontitis and liver cirrhosis. From 35 surface and secreted proteins, 11 CD8[Formula: see text] T cells, 9 CD4[Formula: see text] T cells and 8 B- cell epitopes were identified as antigenic, nonallergenic and nonself. These epitopes were fused with a Cholera Toxin subunit B adjuvant, linkers and a dendritic cell (DC)-targeting peptide to construct a stable and soluble polypeptide vaccine, achieving near-universal population coverage (PC). High-affinity binding to common HLA class I and II alleles was confirmed. Molecular docking revealed strong interactions between the MVC and immune receptors (TLR2-TLR1 and TLR4-MD2), with binding energies of –179.7 ± 9.9 kcal/mol and –221.9 ± 11.5 kcal/mol, respectively. The vaccine construct demonstrated stability and dynamic resilience in molecular dynamic simulations, while immune simulations predicted robust activation of innate and adaptive immune responses in the host. This MVC represents a promising therapeutic candidate against DSV-associated diseases, warranting experimental validation for further development.