An Immunodominant Epitope-Specific Monoclonal Antibody Cocktail Improves Survival in a Mouse Model of Staphylococcus aureus Bacteremia. (22nd September 2020)

• Record Type: Journal Article
• 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
• Is Part Of: Journal of infectious diseases. Volume 223:Number 10(2021)
• Page Start: 1743
• Page End: 1752
• Publication Date: 2020-09-22
• Subjects: methicillin-resistant Staphylococcus aureus -- immunodominant epitope -- monoclonal antibody -- bacteremia; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiaa602
• Languages: English
• ISSNs: 0022-1899

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. Abstract : This work identified 7 B-cell immunodominant epitopes on 4 antigens in the 5-valent Staphylococcus aureus vaccine, including 5 novel epitopes. Four robust monoclonal antibodies (mAbs) against these epitopes were generated and used as an mAb cocktail, which was efficient in combating S. aureus infection.