EMD-40812
Structure of SARS-CoV-2 (HP-GSAS-Mut7) spike in complex with TXG-0078 Fab -Conformation 1
EMD-40812
Single-particle3.17 Å
Deposition: 18/05/2023
Map released: 05/06/2024
Last modified: 26/06/2024
Sample Organism:
Severe acute respiratory syndrome coronavirus 2
Sample: Structure of SARS-CoV-2 (HP-GSAS-Mut7) spike in complex with TXG-0078 Fab -Conformation 1
Deposition Authors: Bangaru S , Ward AB
Sample: Structure of SARS-CoV-2 (HP-GSAS-Mut7) spike in complex with TXG-0078 Fab -Conformation 1
Deposition Authors: Bangaru S , Ward AB
Deep repertoire mining uncovers ultra-broad coronavirus neutralizing antibodies targeting multiple spike epitopes.
Hurtado J,
Rogers TF,
Jaffe DB,
Adams BA,
Bangaru S ,
Garcia E,
Capozzola T,
Messmer T,
Sharma P,
Song G,
Beutler N,
He W,
Dueker K,
Musharrafieh R,
Burbach S,
Truong A,
Stubbington MJT,
Burton DR,
Andrabi R,
Ward AB ,
McDonnell WJ,
Briney B
(2024) Cell Rep , 43 , 114307 - 114307
(2024) Cell Rep , 43 , 114307 - 114307
Abstract:
The development of vaccines and therapeutics that are broadly effective against known and emergent coronaviruses is an urgent priority. We screened the circulating B cell repertoires of COVID-19 survivors and vaccinees to isolate over 9,000 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific monoclonal antibodies (mAbs), providing an expansive view of the SARS-CoV-2-specific Ab repertoire. Among the recovered antibodies was TXG-0078, an N-terminal domain (NTD)-specific neutralizing mAb that recognizes diverse alpha- and beta-coronaviruses. TXG-0078 achieves its exceptional binding breadth while utilizing the same VH1-24 variable gene signature and heavy-chain-dominant binding pattern seen in other NTD-supersite-specific neutralizing Abs with much narrower specificity. We also report CC24.2, a pan-sarbecovirus neutralizing antibody that targets a unique receptor-binding domain (RBD) epitope and shows similar neutralization potency against all tested SARS-CoV-2 variants, including BQ.1.1 and XBB.1.5. A cocktail of TXG-0078 and CC24.2 shows protection in vivo, suggesting their potential use in variant-resistant therapeutic Ab cocktails and as templates for pan-coronavirus vaccine design.
The development of vaccines and therapeutics that are broadly effective against known and emergent coronaviruses is an urgent priority. We screened the circulating B cell repertoires of COVID-19 survivors and vaccinees to isolate over 9,000 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific monoclonal antibodies (mAbs), providing an expansive view of the SARS-CoV-2-specific Ab repertoire. Among the recovered antibodies was TXG-0078, an N-terminal domain (NTD)-specific neutralizing mAb that recognizes diverse alpha- and beta-coronaviruses. TXG-0078 achieves its exceptional binding breadth while utilizing the same VH1-24 variable gene signature and heavy-chain-dominant binding pattern seen in other NTD-supersite-specific neutralizing Abs with much narrower specificity. We also report CC24.2, a pan-sarbecovirus neutralizing antibody that targets a unique receptor-binding domain (RBD) epitope and shows similar neutralization potency against all tested SARS-CoV-2 variants, including BQ.1.1 and XBB.1.5. A cocktail of TXG-0078 and CC24.2 shows protection in vivo, suggesting their potential use in variant-resistant therapeutic Ab cocktails and as templates for pan-coronavirus vaccine design.