An Immunodominant Epitope-Specific Monoclonal Antibody Cocktail Improves Survival in a Mouse Model of<i>Staphylococcus aureus</i>Bacteremia
Hao Zeng, Jinyong Zhang, Xu Song, Jiangmin Zeng, Yue Yuan, Zhifu Chen, Limin Xu, Qiang Gou, Feng Yang, Ni Zeng, Yi Zhang, Liu‐sheng Peng, Liqun Zhao, Jiang Zhu, Yuanyuan Liu, Ping Luo, Quanming Zou, Zhuo Zhao
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.