| Title: |
A broadly generalizable stabilization strategy for sarbecovirus fusion machinery vaccines |
| Authors: |
Jimin Lee, Cameron Stewart, Alexandra Schäfer, Elizabeth M. Leaf, Young-Jun Park, Daniel Asarnow, John M. Powers, Catherine Treichel, Kaitlin R. Sprouse, Davide Corti, Ralph Baric, Neil P. King, David Veesler |
| Source: |
Nature Communications, Vol 15, Iss 1, Pp 1-13 (2024) |
| Publisher Information: |
Nature Portfolio, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Science |
| Subject Terms: |
Science |
| More Details: |
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 S2 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 S2 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) S2 subunits. Immunization of mice with a prefusion-stabilized SARS-CoV-2 S2 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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2041-1723 |
| Relation: |
https://doaj.org/toc/2041-1723 |
| DOI: |
10.1038/s41467-024-49656-5 |
| Access URL: |
https://doaj.org/article/780e43f46b0341b2b056a3f52e383c25 |
| Accession Number: |
edsdoj.780e43f46b0341b2b056a3f52e383c25 |
| Database: |
Directory of Open Access Journals |
