Protective efficacy of the chimeric Staphylococcus aureus vaccine candidate IC in sepsis and pneumonia models.
Protective efficacy of the chimeric Staphylococcus aureus vaccine candidate IC in sepsis and pneumonia models.
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嵌合金黄色葡萄球菌候选疫苗 IC 对脓毒症和肺炎模型的保护功效
DOI：
10.1038/srep20929
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发表时间：
2016-02-11
影响因子：
4.6
通讯作者：
Zeng H
中科院分区：
文献类型：
--
作者：
Yang L;Cai C;Feng Q;Shi Y;Zuo Q;Yang H;Jing H;Wei C;Zhuang Y;Zou Q;Zeng H
金黄色葡萄球菌在世界范围内引起严重的败血症和坏死性肺炎。由于耐多药菌株的传播，开发有效的疫苗是对抗金黄色葡萄球菌感染最有希望的方法。本研究基于铁表面决定因子B （IsdB）和聚集因子A （ClfA）的免疫优势区，设计了新型嵌合疫苗IsdB151-277ClfA33-213 （IC）。与单一成分相比，与AlPO4佐剂配制的IC在金黄色葡萄球菌脓毒症模型中具有更高的保护作用，并且对几种临床金黄色葡萄球菌分离株具有广泛的免疫保护作用。免疫IC诱导强烈的抗体反应。通过调理噬细胞实验（OPA）和被动免疫实验证实了抗体的保护作用。此外，基于细胞因子谱和CD4+ T细胞刺激试验，这种新的嵌合疫苗诱导了Th1/ th17倾斜的细胞免疫反应。单独中和IL-17A（而不是IFN-γ）导致疫苗免疫保护显著降低。最后，我们发现IC对肺炎模型有保护作用。综上所述，这些数据提供的证据表明，IC是一种潜在的有希望的候选疫苗，可用于对抗金黄色葡萄球菌败血症和肺炎。
Staphylococcus aureus causes serious sepsis and necrotic pneumonia worldwide. Due to the spread of multidrug-resistant strains, developing an effective vaccine is the most promising method for combating S. aureus infection. In this study, based on the immune-dominant areas of the iron surface determinant B (IsdB) and clumping factor A (ClfA), we designed the novel chimeric vaccine IsdB151-277ClfA33-213 (IC). IC formulated with the AlPO4 adjuvant induced higher protection in an S. aureus sepsis model compared with the single components alone and showed broad immune protection against several clinical S. aureus isolates. Immunisation with IC induced strong antibody responses. The protective effect of antibodies was demonstrated through the opsonophagocytic assay (OPA) and passive immunisation experiment. Moreover, this new chimeric vaccine induced Th1/Th17-skewed cellular immune responses based on cytokine profiles and CD4+ T cell stimulation tests. Neutralisation of IL-17A alone (but not IFN-γ) resulted in a significant decrease in vaccine immune protection. Finally, we found that IC showed protective efficacy in a pneumonia model. Taken together, these data provide evidence that IC is a potentially promising vaccine candidate for combating S. aureus sepsis and pneumonia.