Department of Biology, Shahed University, Tehran-Qom Express Way, 3319118651, Tehran, Iran.
Applied Microbiology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Sci Rep. 2021 Jan 21;11(1):1914. doi: 10.1038/s41598-021-81356-8.
Acinetobacter baumannii is a serious health threat with a high mortality rate. We have already reported prophylactic effects of IgYs raised against OmpA and Omp34 as well as against inactivated whole-cell (IWC) of A. baumannii in a murine pneumonia model. However, the infection was exacerbated in the mice group that received IgYs raised against the combination of OmpA and Omp34. The current study was conducted to propose reasons for the observed antibody-dependent enhancement (ADE) in addition to the therapeutic effect of specific IgYs in the murine pneumonia model. This phenomenon was hypothetically attributed to topologically inaccessible similar epitopes of OmpA and Omp34 sharing similarity with peptides of mice proteins. In silico analyses revealed that some inaccessible peptides of OmpA shared similarity with peptides of Omp34 and Mus musculus. Specific anti-OmpA and anti-Omp34 IgYs cross-reacted with Omp34 and OmpA respectively. Specific IgYs showed different protectivity against A. baumannii AbI101 in the murine pneumonia model. IgYs triggered against OmpA or IWC of A. baumannii were the most protective antibodies. IgY triggered against Omp34 is ranked next after those against OmpA. The lowest protection was observed in mice received IgYs raised against the combination of rOmpA and rOmp34. In conclusion, specific IgYs against OmpA, Omp34, and IWC of A. baumannii could serve as novel biotherapeutics against A. baumannii pneumonia.
鲍曼不动杆菌是一种严重的健康威胁,死亡率很高。我们已经报道了针对 OmpA 和 Omp34 以及针对鲍曼不动杆菌灭活全细胞(IWC)的 IgY 的预防作用,在小鼠肺炎模型中也是如此。然而,在接受针对 OmpA 和 Omp34 组合的 IgY 治疗的小鼠组中,感染加重了。本研究旨在除了在小鼠肺炎模型中特异性 IgY 的治疗效果之外,提出观察到的抗体依赖性增强(ADE)的原因。这种现象被假设归因于 OmpA 和 Omp34 的拓扑上不可接近的类似表位与小鼠蛋白的肽段具有相似性。计算机分析表明,OmpA 的一些不可接近的肽段与 Omp34 和 Mus musculus 的肽段具有相似性。特异性抗-OmpA 和抗-Omp34 IgY 分别与 Omp34 和 OmpA 发生交叉反应。特异性 IgY 在小鼠肺炎模型中对 AbI101 显示出不同的保护作用。针对 OmpA 或鲍曼不动杆菌 IWC 的 IgY 是最具保护性的抗体。针对 Omp34 的 IgY 仅次于针对 OmpA 的 IgY。在接受针对 rOmpA 和 rOmp34 组合的 IgY 治疗的小鼠中,保护作用最低。总之,针对鲍曼不动杆菌的 OmpA、Omp34 和 IWC 的特异性 IgY 可以作为治疗鲍曼不动杆菌肺炎的新型生物疗法。