In Vivo Delivery of Synthetic Human DNA-Encoded Monoclonal Antibodies Protect against Ebolavirus Infection in a Mouse Model
Summary: 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 di...
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| Format: | Article |
| Language: | English |
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Elsevier
2018-11-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718316516 |
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Article |
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DOAJ |
| language |
English |
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Article |
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DOAJ |
| author |
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 |
| spellingShingle |
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 In Vivo Delivery of Synthetic Human DNA-Encoded Monoclonal Antibodies Protect against Ebolavirus Infection in a Mouse Model Cell Reports |
| author_facet |
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 |
| author_sort |
Ami Patel |
| title |
In Vivo Delivery of Synthetic Human DNA-Encoded Monoclonal Antibodies Protect against Ebolavirus Infection in a Mouse Model |
| title_short |
In Vivo Delivery of Synthetic Human DNA-Encoded Monoclonal Antibodies Protect against Ebolavirus Infection in a Mouse Model |
| title_full |
In Vivo Delivery of Synthetic Human DNA-Encoded Monoclonal Antibodies Protect against Ebolavirus Infection in a Mouse Model |
| title_fullStr |
In Vivo Delivery of Synthetic Human DNA-Encoded Monoclonal Antibodies Protect against Ebolavirus Infection in a Mouse Model |
| title_full_unstemmed |
In Vivo Delivery of Synthetic Human DNA-Encoded Monoclonal Antibodies Protect against Ebolavirus Infection in a Mouse Model |
| title_sort |
in vivo delivery of synthetic human dna-encoded monoclonal antibodies protect against ebolavirus infection in a mouse model |
| publisher |
Elsevier |
| series |
Cell Reports |
| issn |
2211-1247 |
| publishDate |
2018-11-01 |
| description |
Summary: 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. Keywords: DNA-encoded monoclonal antibody, DMAb, monoclonal antibody, Zaire ebolavirus, EBOV, Ebola virus disease, glycoprotein, immunoprophylaxis, DNA, electroporation |
| url |
http://www.sciencedirect.com/science/article/pii/S2211124718316516 |
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doaj-1ccb9ff1c2b54bf9a2b1ef9f657311442020-11-24T21:24:23ZengElsevierCell Reports2211-12472018-11-0125719821993.e4In Vivo Delivery of Synthetic Human DNA-Encoded Monoclonal Antibodies Protect against Ebolavirus Infection in a Mouse ModelAmi Patel0Daniel H. Park1Carl W. Davis2Trevor R.F. Smith3Anders Leung4Kevin Tierney5Aubrey Bryan6Edgar Davidson7Xiaoying Yu8Trina Racine9Charles Reed10Marguerite E. Gorman11Megan C. Wise12Sarah T.C. Elliott13Rianne Esquivel14Jian Yan15Jing Chen16Kar Muthumani17Benjamin J. Doranz18Erica Ollmann Saphire19James E. Crowe20Kate E. Broderick21Gary P. Kobinger22Shihua He23Xiangguo Qiu24Darwyn Kobasa25Laurent Humeau26Niranjan Y. Sardesai27Rafi Ahmed28David B. Weiner29The Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104, USAThe Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104, USAEmory Vaccine Center, Emory University, Atlanta, GA 30317, USAInovio Pharmaceuticals, Plymouth Meeting, PA 19462, USAPublic Health Agency of Canada, Winnipeg, MB R3E 3R2, CanadaPublic Health Agency of Canada, Winnipeg, MB R3E 3R2, CanadaIntegral Molecular, Philadelphia, PA 19104, USAIntegral Molecular, Philadelphia, PA 19104, USAThe Scripps Research Institute, La Jolla, CA 92037, USAPublic Health Agency of Canada, Winnipeg, MB R3E 3R2, Canada; University of Manitoba, Winnipeg, MB R3T 2N2, CanadaInovio Pharmaceuticals, Plymouth Meeting, PA 19462, USAThe Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104, USA; Boston College, Newton, MA 02467, USAInovio Pharmaceuticals, Plymouth Meeting, PA 19462, USAThe Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104, USAThe Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104, USAInovio Pharmaceuticals, Plymouth Meeting, PA 19462, USAInovio Pharmaceuticals, Plymouth Meeting, PA 19462, USAThe Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104, USAIntegral Molecular, Philadelphia, PA 19104, USAThe Scripps Research Institute, La Jolla, CA 92037, USAVanderbilt University, Nashville, TN 37235, USAInovio Pharmaceuticals, Plymouth Meeting, PA 19462, USAUniversité Laval, Quebec City, QC G1V 0A6, CanadaPublic Health Agency of Canada, Winnipeg, MB R3E 3R2, CanadaPublic Health Agency of Canada, Winnipeg, MB R3E 3R2, Canada; University of Manitoba, Winnipeg, MB R3T 2N2, CanadaPublic Health Agency of Canada, Winnipeg, MB R3E 3R2, Canada; University of Manitoba, Winnipeg, MB R3T 2N2, CanadaInovio Pharmaceuticals, Plymouth Meeting, PA 19462, USAInovio Pharmaceuticals, Plymouth Meeting, PA 19462, USAEmory Vaccine Center, Emory University, Atlanta, GA 30317, USAThe Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104, USA; Corresponding authorSummary: 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. Keywords: DNA-encoded monoclonal antibody, DMAb, monoclonal antibody, Zaire ebolavirus, EBOV, Ebola virus disease, glycoprotein, immunoprophylaxis, DNA, electroporationhttp://www.sciencedirect.com/science/article/pii/S2211124718316516 |