James Crowe
Faculty Member
Last active: 3/31/2019

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

Patel A, Park DH, Davis CW, Smith TRF, Leung A, Tierney K, Bryan A, Davidson E, Yu X, Racine T, Reed C, Gorman ME, Wise MC, Elliott STC, Esquivel R, Yan J, Chen J, Muthumani K, Doranz BJ, Saphire EO, Crowe JE, Broderick KE, Kobinger GP, He S, Qiu X, Kobasa D, Humeau L, Sardesai NY, Ahmed R, Weiner DB
Cell Rep. 2018 25 (7): 1982-1993.e4

PMID: 30428362 · PMCID: PMC6319964 · 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.

Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

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