Multiple B-cell epitope vaccine induces a Staphylococcus enterotoxin B-specific IgG1 protective response against MRSA infection.
Multiple B-cell epitope vaccine induces a Staphylococcus enterotoxin B-specific IgG1 protective response against MRSA infection.
复制标题
多 B 细胞表位疫苗可诱导葡萄球菌肠毒素 B 特异性 IgG1 针对 MRSA 感染的保护性反应。
DOI：
10.1038/srep12371
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发表时间：
2015-07-23
影响因子：
4.6
通讯作者：
Wu C
中科院分区：
文献类型：
--
作者：
Zhao Z;Sun HQ;Wei SS;Li B;Feng Q;Zhu J;Zeng H;Zou QM;Wu C
目前还没有针对耐甲氧西林金黄色葡萄球菌（MRSA）的疫苗被批准用于人类。葡萄球菌肠毒素B（SE B）是MRSA最强的外毒素之一。在本研究中，我们评估了SEB多B细胞表位疫苗对MRSA感染的有效性和免疫机制。合成重叠肽ELISA鉴定了三种新的B细胞免疫显性SEB表位（除了先前已知的那些之外）：SEB31 - 48、SEB133 - 150和SEB193 - 210。6个B细胞免疫显性表位（氨基酸残基31 - 48、97 - 114、133 - 150、193 - 210、205 - 222和247 - 261）足以诱导针对MRSA感染的稳健IgG1/IgG2b特异性保护性应答。因此，我们通过组合六个SEB免疫显性表位构建了重组MRSA SEB特异性多B细胞表位疫苗多肽，并证明其能够诱导对MRSA的稳健SEB特异性IgG1应答以及Th2导向同种型应答。此外，多肽诱导的抗血清刺激协同调理吞噬杀死MRSA。最重要的是，多肽在清除MRSA感染小鼠中的细菌方面比整个SEB抗原更有效，并且能够成功地保护小鼠免受各种临床MRSA分离株的感染。总之，这些结果支持进一步评价SEB多B细胞表位疫苗以解决人类MRSA感染。
No vaccine against methicillin-resistant Staphylococcus aureus (MRSA) has been currently approved for use in humans. Staphylococcus enterotoxin B (SEB) is one of the most potent MRSA exotoxins. In the present study, we evaluated the efficacy and immunologic mechanisms of an SEB multiple B-cell epitope vaccine against MRSA infection. Synthetic overlapping peptide ELISA identified three novel B-cell immunodominant SEB epitopes (in addition to those previously known): SEB31–48, SEB133–150, and SEB193–210. Six B-cell immunodominant epitopes (amino acid residues 31–48, 97–114, 133–150, 193–210, 205–222, and 247–261) were sufficient to induce robust IgG1/IgG2b-specific protective responses against MRSA infection. Therefore, we constructed a recombinant MRSA SEB-specific multiple B-cell epitope vaccine Polypeptides by combining the six SEB immunodominant epitopes and demonstrated its ability to induce a robust SEB-specific IgG1 response to MRSA, as well as a Th2-directing isotype response. Moreover, Polypeptides-induced antisera stimulated synergetic opsonophagocytosis killing of MRSA. Most importantly, Polypeptides was more effective at clearing the bacteria in MRSA-infected mice than the whole SEB antigen, and was able to successfully protect mice from infection by various clinical MRSA isolates. Altogether, these results support further evaluation of the SEB multiple B-cell epitope-vaccine to address MRSA infection in humans.