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An Immunodominant Epitope-Specific Monoclonal Antibody Cocktail Improves Survival in a Mouse Model of Staphylococcus aureus Bacteremia.
Journal of Infectious Diseases 2020 September 23
To date, no vaccine or monoclonal antibody (mAb) against S. aureus has been approved for use in humans. Our lab has developed a five-antigen S. aureus vaccine (rFSAV), which is now under efficacy evaluation in a phase II clinical trial. In the current study, using overlapping peptides and antiserum from rFSAV-immunized volunteers, we identified seven B-cell immunodominant epitopes on 4 antigens in rFSAV, including five 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 mAb were used together as a mAb cocktail to prevent MRSA252 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.
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