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

• DOI: 10.1016/j.celrep.2018.10.062
• Publication Date: 2018-11-13T15:44:25Z
• Authors: 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 Sap...; 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
• Keywords: 0301 basic medicine; Mice, Inbred BALB C; QH301-705.5; Muscles; Antibodies, Monoclonal; DNA; Hemorrhagic Fever, Ebola; Ebolavirus; Article; Recombinant Proteins; 3. Good health; Disease Models, Animal; Epitopes; 03 medical and health sciences; HEK293 Cells; Mutagenesis; Animals; Humans; Female; Biology (General); Epitope Mapping; Glycoproteins

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.