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TitleMosaic RBD nanoparticle elicits immunodominant antibody responses across sarbecoviruses.
Journal, issue, pagesCell Rep, Vol. 43, Issue 5, Page 114235, Year 2024
Publish dateMay 28, 2024
AuthorsChuanyu Liu / Senyu Xu / Yuxuan Zheng / Yufeng Xie / Kun Xu / Yan Chai / Tingrong Luo / Lianpan Dai / George F Gao /
PubMed AbstractNanoparticle vaccines displaying mosaic receptor-binding domains (RBDs) or spike (S) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or other sarbecoviruses are used in ...Nanoparticle vaccines displaying mosaic receptor-binding domains (RBDs) or spike (S) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or other sarbecoviruses are used in preparedness against potential zoonotic outbreaks. Here, we describe a self-assembling nanoparticle using lumazine synthase (LuS) as the scaffold to display RBDs from different sarbecoviruses. Mosaic nanoparticles induce sarbecovirus cross-neutralizing antibodies comparable to a nanoparticle cocktail. We find mosaic nanoparticles elicit a B cell receptor repertoire using an immunodominant germline gene pair of IGHV14-3:IGKV14-111. Most of the tested IGHV14-3:IGKV14-111 monoclonal antibodies (mAbs) are broadly cross-reactive to clade 1a, 1b, and 3 sarbecoviruses. Using mAb competition and cryo-electron microscopy, we determine that a representative IGHV14-3:IGKV14-111 mAb, M2-7, binds to a conserved epitope on the RBD, largely overlapping with the pan-sarbecovirus mAb S2H97. This suggests mosaic nanoparticles expand B cell recognition of the common epitopes shared by different clades of sarbecoviruses. These results provide immunological insights into the cross-reactive responses elicited by mosaic nanoparticles against sarbecoviruses.
External linksCell Rep / PubMed:38748880
MethodsEM (single particle)
Resolution3.03 Å
Structure data

38763

8xxw

EMDB-38763, PDB-8xxw:
Fab M2-7 complexed with SARS-Cov2 RBD and human ACE2
Method: EM (single particle) / Resolution: 3.03 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • homo sapiens (human)
  • severe acute respiratory syndrome coronavirus 2
  • mus musculus (house mouse)
KeywordsANTIVIRAL PROTEIN/IMMUNE SYSTEM / antibody viral protein complex / IMMUNE SYSTEM/VIRAL PROTEIN / ANTIVIRAL PROTEIN / ANTIVIRAL PROTEIN-IMMUNE SYSTEM complex

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