8VQB

Prefusion stabilized structure of the SARS-CoV-2 fusion machinery

Summary for 8VQB

• Entry DOI: 10.2210/pdb8vqb/pdb
• EMDB information: 43437
• Descriptor: Spike protein S2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: sarbecoviruses, spike glycoprotein, fusion protein, prefusion-stabilized, seattle structural genomics center for infectious disease, ssgcid, viral protein
• Biological source: Sarbecovirus
• Total number of polymer chains: 3
• Total formula weight: 211336.04

Authors

Lee, J.,Veesler, D.,Seattle Structural Genomics Center for Infectious Disease (SSGCID) (deposition date: 2024-01-18, release date: 2024-07-24)

Primary citation

Lee, J.,Stewart, C.,Schafer, A.,Leaf, E.M.,Park, Y.J.,Asarnow, D.,Powers, J.M.,Treichel, C.,Sprouse, K.R.,Corti, D.,Baric, R.,King, N.P.,Veesler, D.
A broadly generalizable stabilization strategy for sarbecovirus fusion machinery vaccines.
Nat Commun, 15:5496-5496, 2024

PubMed Abstract: Evolution of SARS-CoV-2 alters the antigenicity of the immunodominant spike (S) receptor-binding domain and N-terminal domain, undermining the efficacy of vaccines and antibody therapies. To overcome this challenge, we set out to develop a vaccine focusing antibody responses on the highly conserved but metastable S subunit, which folds as a spring-loaded fusion machinery. We describe a strategy for prefusion-stabilization and high yield recombinant production of SARS-CoV-2 S trimers with native structure and antigenicity. We demonstrate that our design strategy is broadly generalizable to sarbecoviruses, as exemplified with the SARS-CoV-1 (clade 1a) and PRD-0038 (clade 3) S subunits. Immunization of mice with a prefusion-stabilized SARS-CoV-2 S trimer elicits broadly reactive sarbecovirus antibodies and neutralizing antibody titers of comparable magnitude against Wuhan-Hu-1 and the immune evasive XBB.1.5 variant. Vaccinated mice were protected from weight loss and disease upon challenge with XBB.1.5, providing proof-of-principle for fusion machinery sarbecovirus vaccines.

PubMed: 38944664
DOI: 10.1038/s41467-024-49656-5

Experimental method

ELECTRON MICROSCOPY (3 Å)