In vivo delivery of engineered synthetic DNA-encoded SARS-CoV-2 monoclonal antibodies for pre-exposure prophylaxis in non-human primates

ABSTRACTCOVID-19 remains a major public health concern. Monoclonal antibodies have received emergency use authorization (EUA) for pre-exposure prophylaxis against COVID-19 among high-risk groups for treatment of mild to moderate COVID-19. In addition to recombinant biologics, engineered synthetic DN...

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Main Authors: Ami Patel, Kyle Rosenke, Elizabeth M. Parzych, Friederike Feldmann, Suman Bharti, Amanda J. Griffin, Blake Schouest, Matt Lewis, Jihae Choi, Neethu Chokkalingam, Viviane Machado, Brian J. Smith, Drew Frase, Ali R. Ali, Jamie Lovaglio, Brian Nguyen, Patrick W. Hanley, Susanne N. Walker, Ebony N. Gary, Abhijeet Kulkarni, Allison Generotti, Joseph R. Francica, Kim Rosenthal, Daniel W. Kulp, Mark T. Esser, Trevor R. F. Smith, Carl Shaia, David B. Weiner, Heinz Feldmann
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Emerging Microbes and Infections
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/22221751.2023.2294860
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author Ami Patel
Kyle Rosenke
Elizabeth M. Parzych
Friederike Feldmann
Suman Bharti
Amanda J. Griffin
Blake Schouest
Matt Lewis
Jihae Choi
Neethu Chokkalingam
Viviane Machado
Brian J. Smith
Drew Frase
Ali R. Ali
Jamie Lovaglio
Brian Nguyen
Patrick W. Hanley
Susanne N. Walker
Ebony N. Gary
Abhijeet Kulkarni
Allison Generotti
Joseph R. Francica
Kim Rosenthal
Daniel W. Kulp
Mark T. Esser
Trevor R. F. Smith
Carl Shaia
David B. Weiner
Heinz Feldmann
author_facet Ami Patel
Kyle Rosenke
Elizabeth M. Parzych
Friederike Feldmann
Suman Bharti
Amanda J. Griffin
Blake Schouest
Matt Lewis
Jihae Choi
Neethu Chokkalingam
Viviane Machado
Brian J. Smith
Drew Frase
Ali R. Ali
Jamie Lovaglio
Brian Nguyen
Patrick W. Hanley
Susanne N. Walker
Ebony N. Gary
Abhijeet Kulkarni
Allison Generotti
Joseph R. Francica
Kim Rosenthal
Daniel W. Kulp
Mark T. Esser
Trevor R. F. Smith
Carl Shaia
David B. Weiner
Heinz Feldmann
author_sort Ami Patel
collection DOAJ
description ABSTRACTCOVID-19 remains a major public health concern. Monoclonal antibodies have received emergency use authorization (EUA) for pre-exposure prophylaxis against COVID-19 among high-risk groups for treatment of mild to moderate COVID-19. In addition to recombinant biologics, engineered synthetic DNA-encoded antibodies (DMAb) are an important strategy for direct in vivo delivery of protective mAb. A DMAb cocktail was synthetically engineered to encode the immunoglobulin heavy and light chains of two different two different Fc-engineered anti-SARS-CoV-2 antibodies. The DMAbs were designed to enhance in vivo expression and delivered intramuscularly to cynomolgus and rhesus macaques with a modified in vivo delivery regimen. Serum levels were detected in macaques, along with specific binding to SARS-CoV-2 spike receptor binding domain protein and neutralization of multiple SARS-CoV-2 variants of concern in pseudovirus and authentic live virus assays. Prophylactic administration was protective in rhesus macaques against signs of SARS-CoV-2 (USA-WA1/2020) associated disease in the lungs. Overall, the data support further study of DNA-encoded antibodies as an additional delivery mode for prevention of COVID-19 severe disease. These data have implications for human translation of gene-encoded mAbs for emerging infectious diseases and low dose mAb delivery against COVID-19.
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spelling doaj.art-b981edf4969f4fdb9843528b197ac5172024-02-28T16:14:11ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512024-12-0113110.1080/22221751.2023.2294860In vivo delivery of engineered synthetic DNA-encoded SARS-CoV-2 monoclonal antibodies for pre-exposure prophylaxis in non-human primatesAmi Patel0Kyle Rosenke1Elizabeth M. Parzych2Friederike Feldmann3Suman Bharti4Amanda J. Griffin5Blake Schouest6Matt Lewis7Jihae Choi8Neethu Chokkalingam9Viviane Machado10Brian J. Smith11Drew Frase12Ali R. Ali13Jamie Lovaglio14Brian Nguyen15Patrick W. Hanley16Susanne N. Walker17Ebony N. Gary18Abhijeet Kulkarni19Allison Generotti20Joseph R. Francica21Kim Rosenthal22Daniel W. Kulp23Mark T. Esser24Trevor R. F. Smith25Carl Shaia26David B. Weiner27Heinz Feldmann28Vaccine and Immunotherapy Center, The Wistar Institute of Anatomy and Biology, Philadelphia, PA, USARocky Mountain Laboratories, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USAVaccine and Immunotherapy Center, The Wistar Institute of Anatomy and Biology, Philadelphia, PA, USARocky Mountain Laboratories, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USAVaccine and Immunotherapy Center, The Wistar Institute of Anatomy and Biology, Philadelphia, PA, USARocky Mountain Laboratories, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USAInovio Pharmaceuticals, Plymouth Meeting, PA, USARocky Mountain Laboratories, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USAVaccine and Immunotherapy Center, The Wistar Institute of Anatomy and Biology, Philadelphia, PA, USAVaccine and Immunotherapy Center, The Wistar Institute of Anatomy and Biology, Philadelphia, PA, USAInovio Pharmaceuticals, Plymouth Meeting, PA, USARocky Mountain Laboratories, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USAVaccine and Immunotherapy Center, The Wistar Institute of Anatomy and Biology, Philadelphia, PA, USAVaccine and Immunotherapy Center, The Wistar Institute of Anatomy and Biology, Philadelphia, PA, USARocky Mountain Laboratories, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USAInovio Pharmaceuticals, Plymouth Meeting, PA, USARocky Mountain Laboratories, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USAVaccine and Immunotherapy Center, The Wistar Institute of Anatomy and Biology, Philadelphia, PA, USAVaccine and Immunotherapy Center, The Wistar Institute of Anatomy and Biology, Philadelphia, PA, USAVaccine and Immunotherapy Center, The Wistar Institute of Anatomy and Biology, Philadelphia, PA, USAInovio Pharmaceuticals, Plymouth Meeting, PA, USAVaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USAVaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USAVaccine and Immunotherapy Center, The Wistar Institute of Anatomy and Biology, Philadelphia, PA, USAVaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USAInovio Pharmaceuticals, Plymouth Meeting, PA, USARocky Mountain Laboratories, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USAVaccine and Immunotherapy Center, The Wistar Institute of Anatomy and Biology, Philadelphia, PA, USARocky Mountain Laboratories, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USAABSTRACTCOVID-19 remains a major public health concern. Monoclonal antibodies have received emergency use authorization (EUA) for pre-exposure prophylaxis against COVID-19 among high-risk groups for treatment of mild to moderate COVID-19. In addition to recombinant biologics, engineered synthetic DNA-encoded antibodies (DMAb) are an important strategy for direct in vivo delivery of protective mAb. A DMAb cocktail was synthetically engineered to encode the immunoglobulin heavy and light chains of two different two different Fc-engineered anti-SARS-CoV-2 antibodies. The DMAbs were designed to enhance in vivo expression and delivered intramuscularly to cynomolgus and rhesus macaques with a modified in vivo delivery regimen. Serum levels were detected in macaques, along with specific binding to SARS-CoV-2 spike receptor binding domain protein and neutralization of multiple SARS-CoV-2 variants of concern in pseudovirus and authentic live virus assays. Prophylactic administration was protective in rhesus macaques against signs of SARS-CoV-2 (USA-WA1/2020) associated disease in the lungs. Overall, the data support further study of DNA-encoded antibodies as an additional delivery mode for prevention of COVID-19 severe disease. These data have implications for human translation of gene-encoded mAbs for emerging infectious diseases and low dose mAb delivery against COVID-19.https://www.tandfonline.com/doi/10.1080/22221751.2023.2294860SARS-CoV-2monoclonal antibodyDNADNA-encoded monoclonal antibodypreventiongene-encoded antibody
spellingShingle Ami Patel
Kyle Rosenke
Elizabeth M. Parzych
Friederike Feldmann
Suman Bharti
Amanda J. Griffin
Blake Schouest
Matt Lewis
Jihae Choi
Neethu Chokkalingam
Viviane Machado
Brian J. Smith
Drew Frase
Ali R. Ali
Jamie Lovaglio
Brian Nguyen
Patrick W. Hanley
Susanne N. Walker
Ebony N. Gary
Abhijeet Kulkarni
Allison Generotti
Joseph R. Francica
Kim Rosenthal
Daniel W. Kulp
Mark T. Esser
Trevor R. F. Smith
Carl Shaia
David B. Weiner
Heinz Feldmann
In vivo delivery of engineered synthetic DNA-encoded SARS-CoV-2 monoclonal antibodies for pre-exposure prophylaxis in non-human primates
Emerging Microbes and Infections
SARS-CoV-2
monoclonal antibody
DNA
DNA-encoded monoclonal antibody
prevention
gene-encoded antibody
title In vivo delivery of engineered synthetic DNA-encoded SARS-CoV-2 monoclonal antibodies for pre-exposure prophylaxis in non-human primates
title_full In vivo delivery of engineered synthetic DNA-encoded SARS-CoV-2 monoclonal antibodies for pre-exposure prophylaxis in non-human primates
title_fullStr In vivo delivery of engineered synthetic DNA-encoded SARS-CoV-2 monoclonal antibodies for pre-exposure prophylaxis in non-human primates
title_full_unstemmed In vivo delivery of engineered synthetic DNA-encoded SARS-CoV-2 monoclonal antibodies for pre-exposure prophylaxis in non-human primates
title_short In vivo delivery of engineered synthetic DNA-encoded SARS-CoV-2 monoclonal antibodies for pre-exposure prophylaxis in non-human primates
title_sort in vivo delivery of engineered synthetic dna encoded sars cov 2 monoclonal antibodies for pre exposure prophylaxis in non human primates
topic SARS-CoV-2
monoclonal antibody
DNA
DNA-encoded monoclonal antibody
prevention
gene-encoded antibody
url https://www.tandfonline.com/doi/10.1080/22221751.2023.2294860
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