体内递送合成人源 DNA 编码的单克隆抗体可预防小鼠模型中的埃博拉病毒感染。
In Vivo Delivery of Synthetic Human DNA-Encoded Monoclonal Antibodies Protect against Ebolavirus Infection in a Mouse Model.
机构信息
The Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104, USA.
Emory Vaccine Center, Emory University, Atlanta, GA 30317, USA.
出版信息
Cell Rep. 2018 Nov 13;25(7):1982-1993.e4. doi: 10.1016/j.celrep.2018.10.062.
Synthetically engineered DNA-encoded monoclonal antibodies (DMAbs) are an in vivo platform for evaluation and delivery of human mAb to control against infectious disease. Here, we engineer DMAbs encoding potent anti-Zaire ebolavirus (EBOV) glycoprotein (GP) mAbs isolated from Ebola virus disease survivors. We demonstrate the development of a human IgG1 DMAb platform for in vivo EBOV-GP mAb delivery and evaluation in a mouse model. Using this approach, we show that DMAb-11 and DMAb-34 exhibit functional and molecular profiles comparable to recombinant mAb, have a wide window of expression, and provide rapid protection against lethal mouse-adapted EBOV challenge. The DMAb platform represents a simple, rapid, and reproducible approach for evaluating the activity of mAb during clinical development. DMAbs have the potential to be a mAb delivery system, which may be advantageous for protection against highly pathogenic infectious diseases, like EBOV, in resource-limited and other challenging settings.
合成工程化的 DNA 编码单克隆抗体（DMAb）是一种体内平台，用于评估和输送人源单克隆抗体以控制传染病。在这里，我们对从埃博拉病毒病幸存者中分离出的强效抗扎伊尔埃博拉病毒（EBOV）糖蛋白（GP）单克隆抗体进行了工程化改造。我们展示了一种人 IgG1 DMAb 平台的开发，用于在小鼠模型中进行体内 EBOV-GP 单克隆抗体的输送和评估。使用这种方法，我们表明 DMAb-11 和 DMAb-34 表现出与重组单克隆抗体相当的功能和分子特征，具有广泛的表达窗口，并能迅速提供针对致死性适应小鼠的 EBOV 挑战的保护。DMAb 平台代表了一种简单、快速和可重复的方法，可用于在临床开发过程中评估单克隆抗体的活性。DMAb 有可能成为一种单克隆抗体输送系统，在资源有限和其他具有挑战性的环境中，对保护高度致病性传染病（如 EBOV）可能具有优势。
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