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Cell Rep. 2018 Nov 13;25(7):1982-1993.e4. doi: 10.1016/j.celrep.2018.10.062.

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

Author information

1
The Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104, USA.
2
Emory Vaccine Center, Emory University, Atlanta, GA 30317, USA.
3
Inovio Pharmaceuticals, Plymouth Meeting, PA 19462, USA.
4
Public Health Agency of Canada, Winnipeg, MB R3E 3R2, Canada.
5
Integral Molecular, Philadelphia, PA 19104, USA.
6
The Scripps Research Institute, La Jolla, CA 92037, USA.
7
Public Health Agency of Canada, Winnipeg, MB R3E 3R2, Canada; University of Manitoba, Winnipeg, MB R3T 2N2, Canada.
8
The Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104, USA; Boston College, Newton, MA 02467, USA.
9
Vanderbilt University, Nashville, TN 37235, USA.
10
Université Laval, Quebec City, QC G1V 0A6, Canada.
11
The Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104, USA. Electronic address: dweiner@wistar.org.

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.

KEYWORDS:

DMAb; DNA; DNA-encoded monoclonal antibody; EBOV; Ebola virus disease; Zaire ebolavirus; electroporation; glycoprotein; immunoprophylaxis; monoclonal antibody

PMID:
30428362
DOI:
10.1016/j.celrep.2018.10.062
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