The 2013–2016 Ebola outbreak highlighted the limited treatment options and lack of rapid response strategies for emerging pathogen outbreaks. Here, we propose an efficient development cycle using glycoengineered Pichia pastoris to produce monoclonal antibody cocktails against pathogens. To enable rapid genetic engineering of P. pastoris, we introduced a genomic landing pad for reliable recombinase-mediated DNA integration. We then created strains expressing each of the three monoclonal antibodies that comprise the ZMapp cocktail, and demonstrated that the secreted antibodies bind to the Ebola virus glycoprotein by immunofluorescence assay. We anticipate that this approach could accelerate the production of therapeutics against future pathogen outbreaks.

中文翻译：

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巴斯德毕赤酵母中功能性抗埃博拉抗体的生产

2013-2016年埃博拉疫情突显出新兴病原体暴发的治疗方案有限，缺乏快速反应策略。在这里，我们建议使用糖工程毕赤酵母生产有效的开发周期，以产生针对病原体的单克隆抗体混合物。为了能够快速进行巴斯德毕赤酵母的基因工程改造，我们引入了基因组着陆垫，用于可靠的重组酶介导的DNA整合。然后，我们创建了可表达组成ZMapp鸡尾酒的三种单克隆抗体中每一种的菌株，并通过免疫荧光分析证明了分泌的抗体与埃博拉病毒糖蛋白结合。我们预计这种方法可以加快针对未来病原体暴发的疗法的生产。