An Immunodominant Epitope-Specific Monoclonal Antibody Cocktail Improves Survival in a Mouse Model of Staphylococcus aureus Bacteremia
An Immunodominant Epitope-Specific Monoclonal Antibody Cocktail Improves Survival in a Mouse Model of Staphylococcus aureus Bacteremia
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DOI：
10.1093/infdis/jiaa602
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发表时间：
2021-05-15
影响因子：
6.4
通讯作者：
Zhao, Zhuo
中科院分区：
文献类型：
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作者：
Zeng, Hao;Zhang, Jinyong;Zhao, Zhuo
迄今为止，还没有针对金黄色葡萄球菌的疫苗或单克隆抗体 (mAb) 被批准用于人类。我们实验室开发了五抗原金黄色葡萄球菌疫苗（rFSAV），目前正在二期临床试验中进行疗效评价。在当前的研究中，使用来自rFSAV免疫志愿者的重叠肽和抗血清，我们在rFSAV的4个抗原上鉴定了7个B细胞免疫显性表位，包括5个新表位（Hla（48-65）、IsdB（402-419）、IsdB（432-449）、SEB78-95和MntC（7-24））。针对这些表位生成了十种免疫显性表位单克隆抗体，它们都在小鼠脓毒症模型中表现出部分保护作用。四种强效单克隆抗体一起作为单克隆抗体混合物使用，以预防耐甲氧西林金黄色葡萄球菌菌株 252 感染。结果表明，mAb 混合物可有效对抗金黄色葡萄球菌感染，其保护功效与细菌负荷的减少和感染病理的减少相关，这表明 mAb 混合物是一种有前途的金黄色葡萄球菌疫苗候选物。
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 (Hla(48-65), IsdB(402-419), IsdB(432-449), SEB78-95, and MntC(7-24)). 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.