Design And Immune Effect Of Staphylococcus Aureus Vaccine Based On Polysaccharide Adjuvant SI-301

Staphylococcus aureus(S.aureus)is one of the most common pathogenic bacteria,which can cause skin infection,bacterial pneumonia,septicemia,sepsis and other diseases.In recent decades,the prevention and treatment of S.aureus infection is mainly based on the use of antibiotics.However,the abuse of antibiotics leads to the emergence of drug-resistant S.aureus,which increases the difficulty of the treatment of S.aureus infection.The development of new vaccines is of great significance for the prevention of S.aureus infection.As an important part of vaccines,immune adjuvants play an important role in anti-infection immune protection.As an important part of vaccines,immune adjuvants play an important role in anti-infection immune protection.Traditional immune adjuvants,including aluminum adjuvants,have different degrees of toxic side effects,so it is urgent to develop new safe and effective immune adjuvants.Our research group found that bacterial exocytopolysaccharide(SI301)can effectively enhance the immune response without any side effects.Based on the previous research basis,this study developed a new vaccine based on SI301 immune adjuvant combined with Staphylococcus aureus antigen Mnt C(r Mnt C-SI301).r Mnt C-SI301 vaccine was inoculated subcutaneously with female mice aged 6 to 8weeks.The immune protection effect of r Mnt C-SI301 vaccine on the skin infection induced by Staphylococcus aureus in mice was systematically evaluated by detecting the damage area,bacterial load at the damage site,H&E staining pathology and related inflammatory cytokines.The immune response induced by r Mnt C-SI301 vaccine was studied by ELISA detection of serum Ig G and spleen cytokines.In addition,flow cytometry was used to analyze the cellular immune response induced by r Mnt C-SI301 vaccine,and TCRγ/δ-/-,IL-17A-/-,IFN-γ-/-mice were used to verify the immune protective effect of r Mnt C-SI301 vaccine.The results showed that r Mnt C-SI301 vaccine could significantly increase the level of antigen-specific Ig G in mouse serum.Compared with mice immunized with aluminum adjuvant,the levels of IL-17 A and IFN-γ in spleen of mice immunized with r Mnt C-SI301 were significantly increased.Flow cytometry showed that r Mnt CSI301 vaccine could significantly increase the number of γδ T and CD4+ T cells secreted by IL-17 A in the spleen of mice.In the model of Staphylococcus aureus skin infection,r Mnt C-SI301 vaccine can significantly reduce the amount of S.aureus bacteria in the lesion site of the back of mice.The lesion area of the injury site was significantly reduced.Mice with IL-17 A,IFN-γ and γδT gene deletion were further used to verify the immune protective mechanism of r Mnt C-SI301.Compared with mice with WT and IFN-γ-/-,After immunized with IL-17A-/-and TCRγ/δ-/-,r Mnt CSI301 mice infected with S.aureus showed a significant decrease in skin healing rate and a significant increase in bacterial load at the site of infection,indicating that the immune protection of r Mnt C-SI301 vaccine is directly related to γδ T cells and IL-17 A.In this study,the bacterial exopolypolysaccharide adjuvant SI301 combined with S.aureus antigen vaccine has a high immunoprotective effect on S.aureus skin infection,and it is related to the immune response mediated by γδ T cells and IL-17 A.This study provides a theoretical basis for the development of Staphylococcus aureus vaccine.