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Mosaic RBD nanoparticle elicits immunodominant antibody responses across sarbecoviruses

ABSTRACT: Universal vaccines cross-protecting against sarbecoviruses including SARS-CoV-2 are in great need under continuous emergence of SARS-CoV-2 variants and potential novel coronavirus. Nanoparicle vaccines displaying mosaic receptor-binding domains (RBDs) or spike (S) proteins from SARS-CoV-2 and other sarbecoviruses were used for preparedness to emergent zoonotic outbreak. Here, we describe a self-assembling nanoparticle using lumazine synthase (LuS) as the scaffold to display RBDs from different sarbecoviruses. The mosaic LuS-RBD vaccines induced cross-reactive binding and neutralizing antibody responses to sarbecoviruses. Single B cell sequencing revealed that mosaic LuS-RBD elicited B-cell receptor (BCR) repertoire using an immunodominant germline gene pair of IGHV14-3: IGKV14-111 in mice. Most of the tested IGHV14-3: IGKV14-111 monoclonal antibodies (mAbs) are broadly cross-reactive to the clade 1a, 1b and 3 sarbecoviruses. By antibody binning and cryo-electron microscopy, we determined a reprensentative IGHV14-3: IGKV14-111 mAb, M2-7, bound to an conserved epitope on RBD largely overlapping with a pan-sarbecovirus mAb S2H97, which suggested that mosaic nanoparticles expended B cells recognizing the common epitopes shared by different clades of sarbecoviruses. These results provide immunological insights into the cross-reactive responses elicited by mosaic nanoparticle against emerging sarbecoviruses.

ORGANISM(S): Mus musculus

PROVIDER: GSE240940 | GEO | 2024/05/12

REPOSITORIES: GEO

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