A broadly generalizable stabilization strategy for sarbecovirus fusion machinery vaccines.

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

SUBMITTER: Lee J 

PROVIDER: S-EPMC11214633 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature