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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Format: | Article |
Language: | English |
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Taylor & Francis Group
2024-12-01
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Series: | Emerging Microbes and Infections |
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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. |
first_indexed | 2024-03-07T19:48:42Z |
format | Article |
id | doaj.art-b981edf4969f4fdb9843528b197ac517 |
institution | Directory Open Access Journal |
issn | 2222-1751 |
language | English |
last_indexed | 2024-03-07T19:48:42Z |
publishDate | 2024-12-01 |
publisher | Taylor & Francis Group |
record_format | Article |
series | Emerging Microbes and Infections |
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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