Structure-based design of a highly stable, covalently-linked SARS-CoV-2 spike trimer with improved structural properties and immunogenicity
Olmedillas, E.; Mann, C. J.; Peng, W.; Wang, Y.-T.; Diaz Avalos, R.; Bedinger, D.; Valentine, K.; Shafee, N.; Schendel, S. L.; Yuan, M.; Lang, G.; Rouet, R.; Christ, D.; Jiang, W.; Wilson, I. A.; Germann, T.; Shresta, S.; Snijder, J.; Ollmann Saphire, E.
Show abstract
The continued threat of SARS-CoV-2 to global health necessitates development of improved research tools and vaccines. We present an improved SARS-CoV-2 spike ectodomain, "VFLIP", bearing five proline substitutions, a flexible cleavage site linker, and an inter-protomer disulfide bond. VFLIP displays significantly improved stability, high-yield production and retains its trimeric state without exogenous trimerization motifs. High-resolution cryo-EM and glycan profiling reveal that the VFLIP quaternary structure and glycosylation mimic the native spike on the viral surface. Further, VFLIP has enhanced affinity and binding kinetics relative to other stabilized spike proteins for antibodies in the Coronavirus Immunotherapeutic Consortium (CoVIC), and mice immunized with VFLIP exhibit potent neutralizing antibody responses against wild-type and B.1.351 live SARS-CoV-2. Taken together, VFLIP represents an improved tool for diagnostics, structural biology, antibody discovery, and vaccine design.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- Structural conservation of Lassa virus glycoproteins and recognition by neutralizing antibodies 97%
- Antigen spacing on protein nanoparticles influences antibody responses to vaccination 97%
- Convergence of a common solution to broad ebolavirus neutralization by glycan cap directed human antibodies 97%
Similar papers in this journal
- Structure selected RBM immunogens prime polyclonal memory responses that neutralize SARS-CoV-2 variants of concern 96%
- A combination of potently neutralizing monoclonal antibodies isolated from an Indian convalescent donor protects against the SARS-CoV-2 delta variant 95%
- Engineering well-expressed, V2-immunofocusing HIV-1 envelope glycoprotein membrane trimers for use in heterologous prime-boost vaccine regimens 95%
Similar papers in this journal
- Nanobody repertoire generated against the spike protein of ancestral SARS-CoV-2 remains efficacious against the rapidly evolving virus 97%
- Nanobody Repertoires for Exposing Vulnerabilities of SARS-CoV-2 96%
- Functional characterization and lineage analysis of broadly neutralizing human antibodies against dengue virus identified by single B cell transcriptomics 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.