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  • In Vivo Delivery of Synthetic Human DNA-Encoded Monoclonal Antibodies Protect against Ebolavirus Infection in a Mouse Model.

In Vivo Delivery of Synthetic Human DNA-Encoded Monoclonal Antibodies Protect against Ebolavirus Infection in a Mouse Model.

Cell reports (2018-11-15)
Ami Patel, Daniel H Park, Carl W Davis, Trevor R F Smith, Anders Leung, Kevin Tierney, Aubrey Bryan, Edgar Davidson, Xiaoying Yu, Trina Racine, Charles Reed, Marguerite E Gorman, Megan C Wise, Sarah T C Elliott, Rianne Esquivel, Jian Yan, Jing Chen, Kar Muthumani, Benjamin J Doranz, Erica Ollmann Saphire, James E Crowe, Kate E Broderick, Gary P Kobinger, Shihua He, Xiangguo Qiu, Darwyn Kobasa, Laurent Humeau, Niranjan Y Sardesai, Rafi Ahmed, David B Weiner
ABSTRACT

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.

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Sigma-Aldrich
Anti-Human IgG (H+L)-Peroxidase antibody produced in donkey, affinity isolated antibody, lyophilized powder
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