8D8R

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

8D8R の概要

• エントリーDOI: 10.2210/pdb8d8r/pdb
• EMDBエントリー: 27254 27255
• 分子名称: 2196 light chain, 2196 heavy chain, Spike glycoprotein, ... (4 entities in total)
• 機能のキーワード: covid-19, sars-cov-2, spike, rbd, igg, dmab, antibody cocktail, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 179535.24

構造登録者

Du, J.,Cui, J.,Pallesen, J. (登録日: 2022-06-08, 公開日: 2022-10-19, 最終更新日: 2024-11-06)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (4.1 Å)