An Immunodominant Epitope-Specific Monoclonal Antibody Cocktail Improves Survival in a Mouse Model of Staphylococcus aureus Bacteremia

Abstract

Abstract To date, no vaccine or monoclonal antibody (mAb) against Staphylococcus aureus has been approved for use in humans. Our laboratory has developed a 5-antigen S. aureus vaccine (rFSAV), which is now under efficacy evaluation in a phase 2 clinical trial. In the current study, using overlapping peptides and antiserum from rFSAV-immunized volunteers, we identified 7 B-cell immunodominant epitopes on 4 antigens in rFSAV, including 5 novel epitopes (Hla48-65, IsdB402-419, IsdB432-449, SEB78-95, and MntC7-24). Ten immunodominant epitope mAbs were generated against these epitopes, and all of them exhibited partial protection in a mouse sepsis model. Four robust mAbs were used together as an mAb cocktail to prevent methicillin-resistant S. aureus strain 252 infection. The results showed that the mAb cocktail was efficient in combating S. aureus infection and that its protective efficacy correlated with a reduced bacterial burden and decreased infection pathology, which demonstrates that the mAb cocktail is a promising S. aureus vaccine candidate.