Immunogenicity Of A Multi-epitope Vaccine Based On Staphylococcus Aureus IsdB, TraP And FnBPA

Staphylococcus aureus(S. aureus) is one of the common pathogens causing skin and soft tissue infections. Drug resistance of strains is more and more serious, which leads to ineffective antibacterial drug treatment, so that vaccine immunization has become a better choice to prevent the infection of S. aureus. Pathogenic factor of S. aureus is numerous and previous vaccines tend to induce humoral immune response, resulting in poor immune protection effect. It has been proved that CD4+ T-cell, especially Th1/Th17, immune responses play a major role in the process of preventing S. aureus infections. Therefore, it is necessary to study the immunogenicity and immune protection of multi-epitope vaccines that prime CD4+ T cell and induce dominant Th1/Th17 responses.Iron-regulated surface determinant B(IsdB) of S. aureus is a highly conserved surface protein that can induce protective CD4+ T-cell immune response. But CD4+ T-cell epitopes on the S. aureus IsdB have not been well identified. In this study, MHC binding assay was used to predict CD4+ T-cell epitopes on S. aureus IsdB protein, and six peptides were synthesized to validate the potential epitopes. CD4+ T-cells stimulated with peptides P1 and P4 secreted significantly higher levels of IFN-γ and IL-17 A. However, the levels of the cytokine IL-4 and IL-10 almost remained unchanged, suggesting that P1 and P4 preferentially elicited polarized Th1 / Th17-type responses. In addition, BALB/c mice only responded to P4, but not P1; while C57BL/6 mice responded to P1, not P4. This implied that epitope P1 and P4 were H-2b and H-2d restricted epitope, respectively.Based on the above research, we constructed and evaluated the immunogenicity of an epitope-based antigen, and invenstigated if its potential application against S. aureus infection.The multi-epitope vaccine named ITF was composed of tandem copies of four CD4+ T-cell epitopes(IsdB159-178, IsdB287-306, TraP20-39 and TraP94-113) and three linear B-cell epitopes(TraP154-163, FnbpA352-364 and FnbpA763-772) from S. aureus. We tested the ability of the novel vaccination to induce immune responses in BALB/c and C57BL/6 mice and its protective efficacy against S. aureus infection. Immunization with the multi-epitope vaccine induced strong antibody and T cell responses. The multi-epitope vaccine showed a stronger protective immuneresponse than the control(pET32a). The results indicated that the multi-epitope vaccine could be a promising vaccine for the prevention from S. aureus infections.