DNA-delivered antibody cocktail exhibits improved pharmacokinetics and confers prophylactic protection against SARS-CoV-2

Elizabeth M. Parzych, Jianqiu Du, Ali R. Ali, Katherine Schultheis, Drew Frase, Trevor R. F. Smith, Jiayan Cui, Neethu Chokkalingam, Nicholas J. Tursi, Viviane M. Andrade, Bryce M. Warner, Ebony N. Gary, Yue Li, Jihae Choi, Jillian Eisenhauer, Igor Maricic, Abhijeet Kulkarni, Jacqueline D. Chu, Gabrielle Villafana, Kim Rosenthal, Kuishu Ren, Joseph R. Francica, Sarah K. Wootton, Pablo Tebas, Darwyn Kobasa, Kate E. Broderick, Jean D. Boyer, Mark T. Esser, Jesper Pallesen, Dan W. Kulp, Ami Patel and David B. Weiner ()
Additional contact information
Elizabeth M. Parzych: The Wistar Institute of Anatomy and Biology
Jianqiu Du: Indiana University
Ali R. Ali: The Wistar Institute of Anatomy and Biology
Katherine Schultheis: Inovio Pharmaceuticals
Drew Frase: The Wistar Institute of Anatomy and Biology
Trevor R. F. Smith: Inovio Pharmaceuticals
Jiayan Cui: Indiana University
Neethu Chokkalingam: The Wistar Institute of Anatomy and Biology
Nicholas J. Tursi: The Wistar Institute of Anatomy and Biology
Viviane M. Andrade: Inovio Pharmaceuticals
Bryce M. Warner: Public Health Agency of Canada
Ebony N. Gary: The Wistar Institute of Anatomy and Biology
Yue Li: The Wistar Institute of Anatomy and Biology
Jihae Choi: The Wistar Institute of Anatomy and Biology
Jillian Eisenhauer: The Wistar Institute of Anatomy and Biology
Igor Maricic: Inovio Pharmaceuticals
Abhijeet Kulkarni: The Wistar Institute of Anatomy and Biology
Jacqueline D. Chu: The Wistar Institute of Anatomy and Biology
Gabrielle Villafana: The Wistar Institute of Anatomy and Biology
Kim Rosenthal: BioPharmaceuticals R&D, AstraZeneca
Kuishu Ren: BioPharmaceuticals R&D, AstraZeneca
Joseph R. Francica: BioPharmaceuticals R&D, AstraZeneca
Sarah K. Wootton: University of Guelph
Pablo Tebas: University of Pennsylvania
Darwyn Kobasa: Public Health Agency of Canada
Kate E. Broderick: Inovio Pharmaceuticals
Jean D. Boyer: Inovio Pharmaceuticals
Mark T. Esser: BioPharmaceuticals R&D, AstraZeneca
Jesper Pallesen: Indiana University
Dan W. Kulp: The Wistar Institute of Anatomy and Biology
Ami Patel: The Wistar Institute of Anatomy and Biology
David B. Weiner: The Wistar Institute of Anatomy and Biology

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: Abstract Monoclonal antibody therapy has played an important role against SARS-CoV-2. Strategies to deliver functional, antibody-based therapeutics with improved in vivo durability are needed to supplement current efforts and reach underserved populations. Here, we compare recombinant mAbs COV2-2196 and COV2-2130, which compromise clinical cocktail Tixagevimab/Cilgavimab, with optimized nucleic acid-launched forms. Functional profiling of in vivo-expressed, DNA-encoded monoclonal antibodies (DMAbs) demonstrated similar specificity, broad antiviral potency and equivalent protective efficacy in multiple animal challenge models of SARS-CoV-2 prophylaxis compared to protein delivery. In PK studies, DNA-delivery drove significant serum antibody titers that were better maintained compared to protein administration. Furthermore, cryo-EM studies performed on serum-derived DMAbs provide the first high-resolution visualization of in vivo-launched antibodies, revealing new interactions that may promote cooperative binding to trimeric antigen and broad activity against VoC including Omicron lineages. These data support the further study of DMAb technology in the development and delivery of valuable biologics.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33309-6

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DOI: 10.1038/s41467-022-33309-6

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