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

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 SaphireJames E. Crowe, Kate E. Broderick, Gary P. Kobinger, Shihua He, Xiangguo Qiu, Darwyn Kobasa, Laurent Humeau, Niranjan Y. Sardesai, Rafi Ahmed, David B. Weiner

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

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. Monoclonal antibodies are an important approach for emerging infectious disease prevention. Patel et al. demonstrate engineering and in vivo delivery of DNA-encoded monoclonal antibodies (DMAbs) targeting the Zaire ebolavirus (EBOV) glycoprotein. DMAbs protect against lethal mouse-adapted EBOV and are useful for rapid evaluation of fully human mAbs in live animal models.

Original languageEnglish (US)
Pages (from-to)1982-1993.e4
JournalCell Reports
Volume25
Issue number7
DOIs
StatePublished - Nov 13 2018
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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