DNA-delivered antibody cocktail exhibits improved pharmacokinetics and confers prophylactic protection against SARS-CoV-2
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 06, 2022
- Source ID
- 10.1038/s41467-022-33309-6
Entities
People
- Abhijeet Kulkarni
- Ali R. Ali
- Ami Patel
- Bryce M. Warner
- Daniel W Kulp
- Darwyn Kobasa
- David B. Weiner
- Drew Frase
- Ebony N Gary
- Elizabeth M. Parzych
- Gabrielle Villafana
- Igor Maricic
- Jacqueline D. Chu
- Jean D. Boyer
- Jesper Pallesen
- Jianqiu Du
- Jiayan Cui
- Jihae Choi
- Jillian Eisenhauer
- Joseph R. Francica
- Kate E. Broderick
- Katherine Schultheis
- Kim Rosenthal
- Kuishu Ren
- Mark T Esser
- Neethu Chokkalingam
- Nicholas Tursi
- Pablo Tebas
- Sarah K Wootton
- Trevor R F Smith
- Viviane M. Andrade
- Yue Li
Organizations
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases
- National Institutes of Health
- Public Health Agency of Canada
- United States Department of Defense