Abstract

COVID-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.

Details

Title
In vivo delivery of engineered synthetic DNA-encoded SARS-CoV-2 monoclonal antibodies for pre-exposure prophylaxis in non-human primates
Author
Patel, Ami 1 ; Rosenke, Kyle 2 ; Parzych, Elizabeth M 1 ; Feldmann, Friederike 2 ; Bharti, Suman 1 ; Griffin, Amanda J 2 ; Blake Schouest 3 ; Lewis, Matt 2 ; Choi, Jihae 1 ; Chokkalingam, Neethu 1 ; Machado, Viviane 3 ; Smith, Brian J 2 ; Frase, Drew 1 ; Ali, Ali R 1 ; Lovaglio, Jamie 2 ; Nguyen, Brian 3 ; Hanley, Patrick W 2 ; Walker, Susanne N 1 ; Gary, Ebony N 1 ; Kulkarni, Abhijeet 1 ; Generotti, Allison 3 ; Francica, Joseph R 4 ; Rosenthal, Kim 4 ; Kulp, Daniel W 1 ; Esser, Mark T 4 ; Smith, Trevor R F 3 ; Shaia, Carl 2   VIAFID ORCID Logo  ; Weiner, David B 1 ; Feldmann, Heinz 2   VIAFID ORCID Logo 

1  Vaccine and Immunotherapy Center, The Wistar Institute of Anatomy and Biology, Philadelphia, PA, USA 
2  Rocky Mountain Laboratories, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA 
3  Inovio Pharmaceuticals, Plymouth Meeting, PA, USA 
4  Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA 
Publication year
2024
Publication date
Dec 2024
Publisher
Taylor & Francis Ltd.
e-ISSN
22221751
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1080/22221751.2023.2294860
ProQuest document ID
3142112423
Copyright
© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd. This work is licensed under the Creative Commons  Attribution – Non-Commercial License http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.