Epitope-based immunoinformatics study of a novel Hla-MntC-SACOL0723 fusion protein from Staphylococcus aureus: Induction of multi-pattern immune responses

摘要

Staphylococcus aureus infections are now one of the most common causes of surgical drainage, bacteremia, and hospital-acquired infections. The emergence of antibiotic resistance has increased mortality and costs of treatment. The design of a new vaccine against S. aureus would have a great beneficial impact on public health. In the current report, we design and introduce a novel epitope-based fusion protein (Hla, MntC and SACOL0723) and investigate its biological activities. Three known antigenic proteins from S. aureus were analyzed for the prediction of immunogenic B and T-cell epitopes and validated using bioinformatics tools. The affinity and the map of interactions between the receptor and ligand were evaluated via docking protocols. Functional activity of the recombinant protein was assessed by western blot and opsonophagocytosis tests and determining the bacterial burden from the infected tissues. To determine the type of induced immunity, cytokines profile and isotyping ELISA was performed. Based on in silico analysis, seven epitopes rich domain including highly scored T and B-cell epitopes were selected. The study results indicated that the high titer of specific antibodies raised against the vaccine candidate could opsonize the bacteria and decrease the viable bacterial cells. The fusion protein was able to elicit a mixture of Th1, Th2, and Th17 immune responses more towards Th1 and Th17. In conclusion, the fusion protein formulated with alum could be considered as a potential vaccine candidate for protection against S. aureus in the near future.