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

Autor: Parzych EM; The Vaccine and Immunotherapy Center, The Wistar Institute of Anatomy and Biology, Philadelphia, PA, 19104, USA., Du J; Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, IN, 47405, USA., Ali AR; The Vaccine and Immunotherapy Center, The Wistar Institute of Anatomy and Biology, Philadelphia, PA, 19104, USA., Schultheis K; Inovio Pharmaceuticals, Plymouth Meeting, PA, 19462, USA., Frase D; The Vaccine and Immunotherapy Center, The Wistar Institute of Anatomy and Biology, Philadelphia, PA, 19104, USA., Smith TRF; Inovio Pharmaceuticals, Plymouth Meeting, PA, 19462, USA., Cui J; Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, IN, 47405, USA., Chokkalingam N; The Vaccine and Immunotherapy Center, The Wistar Institute of Anatomy and Biology, Philadelphia, PA, 19104, USA., Tursi NJ; The Vaccine and Immunotherapy Center, The Wistar Institute of Anatomy and Biology, Philadelphia, PA, 19104, USA., Andrade VM; Inovio Pharmaceuticals, Plymouth Meeting, PA, 19462, USA., Warner BM; Public Health Agency of Canada, Winnipeg, MB, R3E 3R2, Canada., Gary EN; The Vaccine and Immunotherapy Center, The Wistar Institute of Anatomy and Biology, Philadelphia, PA, 19104, USA., Li Y; The Vaccine and Immunotherapy Center, The Wistar Institute of Anatomy and Biology, Philadelphia, PA, 19104, USA., Choi J; The Vaccine and Immunotherapy Center, The Wistar Institute of Anatomy and Biology, Philadelphia, PA, 19104, USA., Eisenhauer J; The Vaccine and Immunotherapy Center, The Wistar Institute of Anatomy and Biology, Philadelphia, PA, 19104, USA., Maricic I; Inovio Pharmaceuticals, Plymouth Meeting, PA, 19462, USA., Kulkarni A; The Vaccine and Immunotherapy Center, The Wistar Institute of Anatomy and Biology, Philadelphia, PA, 19104, USA., Chu JD; The Vaccine and Immunotherapy Center, The Wistar Institute of Anatomy and Biology, Philadelphia, PA, 19104, USA., Villafana G; The Vaccine and Immunotherapy Center, The Wistar Institute of Anatomy and Biology, Philadelphia, PA, 19104, USA., Rosenthal K; Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, 20878, USA., Ren K; Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, 20878, USA., Francica JR; Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, 20878, USA., Wootton SK; Department of Pathobiology, University of Guelph, Guelph, ON, N1G 2W1, Canada., Tebas P; University of Pennsylvania, Philadelphia, PA, 19104, USA., Kobasa D; Public Health Agency of Canada, Winnipeg, MB, R3E 3R2, Canada.; Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, R3E 0J9, Canada., Broderick KE; Inovio Pharmaceuticals, Plymouth Meeting, PA, 19462, USA., Boyer JD; Inovio Pharmaceuticals, Plymouth Meeting, PA, 19462, USA., Esser MT; Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, 20878, USA., Pallesen J; Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, IN, 47405, USA., Kulp DW; The Vaccine and Immunotherapy Center, The Wistar Institute of Anatomy and Biology, Philadelphia, PA, 19104, USA., Patel A; The Vaccine and Immunotherapy Center, The Wistar Institute of Anatomy and Biology, Philadelphia, PA, 19104, USA., Weiner DB; The Vaccine and Immunotherapy Center, The Wistar Institute of Anatomy and Biology, Philadelphia, PA, 19104, USA. dweiner@wistar.org.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Oct 06; Vol. 13 (1), pp. 5886. Date of Electronic Publication: 2022 Oct 06.
DOI: 10.1038/s41467-022-33309-6
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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