8YRP

SARS-CoV-2 Delta Spike in complex with JM-1A

Summary for 8YRP

• Entry DOI: 10.2210/pdb8yrp/pdb
• Related: 8X0Y 8YRO 8YZ5 8YZ6
• EMDB information: 39547
• Descriptor: Spike glycoprotein, JM-1A Heavy Chain, JM-1A Light Chain (3 entities in total)
• Functional Keywords: antibody, viral protein-immune system complex, viral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 5
• Total formula weight: 441952.03

Authors

Nguyen, V.H.T.,Chen, X. (deposition date: 2024-03-21, release date: 2024-06-05, Last modification date: 2024-10-30)

Primary citation

Chen, X.,Mohapatra, A.,Nguyen, H.T.V.,Schimanski, L.,Kit Tan, T.,Rijal, P.,Chen, C.P.,Cheng, S.H.,Lee, W.H.,Chou, Y.C.,Townsend, A.R.,Ma, C.,Huang, K.A.
The presence of broadly neutralizing anti-SARS-CoV-2 RBD antibodies elicited by primary series and booster dose of COVID-19 vaccine.
Plos Pathog., 20:e1012246-e1012246, 2024

PubMed Abstract: Antibody-mediated immunity plays a key role in protection against SARS-CoV-2. We characterized B-cell-derived anti-SARS-CoV-2 RBD antibody repertoires from vaccinated and infected individuals and elucidate the mechanism of action of broadly neutralizing antibodies and dissect antibodies at the epitope level. The breadth and clonality of anti-RBD B cell response varies among individuals. The majority of neutralizing antibody clones lose or exhibit reduced activities against Beta, Delta, and Omicron variants. Nevertheless, a portion of anti-RBD antibody clones that develops after a primary series or booster dose of COVID-19 vaccination exhibit broad neutralization against emerging Omicron BA.2, BA.4, BA.5, BQ.1.1, XBB.1.5 and XBB.1.16 variants. These broadly neutralizing antibodies share genetic features including a conserved usage of the IGHV3-53 and 3-9 genes and recognize three clustered epitopes of the RBD, including epitopes that partially overlap the classically defined set identified early in the pandemic. The Fab-RBD crystal and Fab-Spike complex structures corroborate the epitope grouping of antibodies and reveal the detailed binding mode of broadly neutralizing antibodies. Structure-guided mutagenesis improves binding and neutralization potency of antibody with Omicron variants via a single amino-substitution. Together, these results provide an immunological basis for partial protection against severe COVID-19 by the ancestral strain-based vaccine and indicate guidance for next generation monoclonal antibody development and vaccine design.

PubMed: 38857264
DOI: 10.1371/journal.ppat.1012246

Experimental method

ELECTRON MICROSCOPY (3.64 Å)