8D8R

SARS-CoV-2 Spike RBD in complex with DMAb 2196

Summary for 8D8R

• Entry DOI: 10.2210/pdb8d8r/pdb
• EMDB information: 27254 27255
• Descriptor: 2196 light chain, 2196 heavy chain, Spike glycoprotein, ... (4 entities in total)
• Functional Keywords: covid-19, sars-cov-2, spike, rbd, igg, dmab, antibody cocktail, viral protein-immune system complex, viral protein/immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 179535.24

Authors

Du, J.,Cui, J.,Pallesen, J. (deposition date: 2022-06-08, release date: 2022-10-19, Last modification date: 2024-11-06)

Primary citation

Parzych, E.M.,Du, J.,Ali, A.R.,Schultheis, K.,Frase, D.,Smith, T.R.F.,Cui, J.,Chokkalingam, N.,Tursi, N.J.,Andrade, V.M.,Warner, B.M.,Gary, E.N.,Li, Y.,Choi, J.,Eisenhauer, J.,Maricic, I.,Kulkarni, A.,Chu, J.D.,Villafana, G.,Rosenthal, K.,Ren, K.,Francica, J.R.,Wootton, S.K.,Tebas, P.,Kobasa, D.,Broderick, K.E.,Boyer, J.D.,Esser, M.T.,Pallesen, J.,Kulp, D.W.,Patel, A.,Weiner, D.B.
DNA-delivered antibody cocktail exhibits improved pharmacokinetics and confers prophylactic protection against SARS-CoV-2.
Nat Commun, 13:5886-5886, 2022

PubMed 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.

PubMed: 36202799
DOI: 10.1038/s41467-022-33309-6

Experimental method

ELECTRON MICROSCOPY (4.1 Å)