Yang Liuyang, Cai Changzhi, Feng Qiang, Shi Yun, Zuo Qianfei, Yang Huijie, Jing Haiming, Wei Chao, Zhuang Yuan, Zou Quanming, Zeng Hao
National Engineering Research Center of Immunological Products &Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, P.R. China.
Department of Biological and Chemical Engineering, Chongqing University of Education, Chongqing 400067, P.R. China.
Sci Rep. 2016 Feb 11;6:20929. doi: 10.1038/srep20929.
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.
金黄色葡萄球菌在全球范围内可引发严重的败血症和坏死性肺炎。由于多重耐药菌株的传播，研发一种有效的疫苗是对抗金黄色葡萄球菌感染最具前景的方法。在本研究中，基于铁表面决定簇B（IsdB）和凝聚因子A（ClfA）的免疫优势区域，我们设计了新型嵌合疫苗IsdB151 - 277ClfA33 - 213（IC）。与单独的单一成分相比，用磷酸铝佐剂配制的IC在金黄色葡萄球菌败血症模型中诱导出更高的保护作用，并对几种临床金黄色葡萄球菌分离株表现出广泛的免疫保护。用IC免疫可诱导强烈的抗体反应。通过调理吞噬试验（OPA）和被动免疫实验证明了抗体的保护作用。此外，基于细胞因子谱和CD4(+) T细胞刺激试验，这种新型嵌合疫苗诱导了Th1/Th17偏向的细胞免疫反应。单独中和IL - 17A（而非IFN - γ）导致疫苗免疫保护作用显著降低。最后，我们发现IC在肺炎模型中显示出保护效果。综上所述，这些数据证明IC是对抗金黄色葡萄球菌败血症和肺炎的一种潜在有前景的疫苗候选物。
