A broadly generalizable stabilization strategy for sarbecovirus fusion machinery vaccines.

ABSTRACT: Continuous 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 monoclonal 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. Here, we describe a protein design strategy enabling prefusion-stabilization of the SARS-CoV-2 S₂ subunit and high yield recombinant expression of trimers with native structure and antigenicity. We demonstrate that our design strategy is broadly generalizable to all sarbecoviruses, as exemplified with the SARS-CoV-1 (clade 1a) and PRD-0038 (clade 3) S₂ fusion machine

SUBMITTER: Lee J 

PROVIDER: S-EPMC10760017 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature