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- Title
An Immunodominant Epitope-Specific Monoclonal Antibody Cocktail Improves Survival in a Mouse Model of Staphylococcus aureus Bacteremia.
- Authors
Zeng, Hao; Zhang, Jinyong; Song, Xu; Zeng, Jiangmin; Yuan, Yue; Chen, Zhifu; Xu, Limin; Gou, Qiang; Yang, Feng; Zeng, Ni; Zhang, Yi; Peng, Liusheng; Zhao, Liqun; Zhu, Jiang; Liu, Yuanyuan; Luo, Ping; Zou, Quanming; Zhao, Zhuo
- 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.
- Subjects
LABORATORY mice; MONOCLONAL antibodies; STAPHYLOCOCCUS aureus; SURVIVAL analysis (Biometry); BACTEREMIA; STAPHYLOCOCCAL disease prevention; BACTEREMIA prevention; BIOLOGICAL models; RESEARCH; ANIMAL experimentation; RESEARCH methodology; BACTERIAL antibodies; METHICILLIN-resistant staphylococcus aureus; EVALUATION research; COMPARATIVE studies; ANTIGENS; MICE
- Publication
Journal of Infectious Diseases, 2021, Vol 223, Issue 10, p1743
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jiaa602