tetano
Editor, Senior Moderator
Cell Rep
. 2024 May 14;43(5):114235.
doi: 10.1016/j.celrep.2024.114235. Online ahead of print. Mosaic RBD nanoparticle elicits immunodominant antibody responses across sarbecoviruses
Chuanyu Liu[SUP] 1 [/SUP], Senyu Xu[SUP] 2 [/SUP], Yuxuan Zheng[SUP] 3 [/SUP], Yufeng Xie[SUP] 3 [/SUP], Kun Xu[SUP] 4 [/SUP], Yan Chai[SUP] 3 [/SUP], Tingrong Luo[SUP] 5 [/SUP], Lianpan Dai[SUP] 6 [/SUP], George F Gao[SUP] 7 [/SUP]
Affiliations
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.
. 2024 May 14;43(5):114235.
doi: 10.1016/j.celrep.2024.114235. Online ahead of print. Mosaic RBD nanoparticle elicits immunodominant antibody responses across sarbecoviruses
Chuanyu Liu[SUP] 1 [/SUP], Senyu Xu[SUP] 2 [/SUP], Yuxuan Zheng[SUP] 3 [/SUP], Yufeng Xie[SUP] 3 [/SUP], Kun Xu[SUP] 4 [/SUP], Yan Chai[SUP] 3 [/SUP], Tingrong Luo[SUP] 5 [/SUP], Lianpan Dai[SUP] 6 [/SUP], George F Gao[SUP] 7 [/SUP]
Affiliations
- PMID: 38748880
- DOI: 10.1016/j.celrep.2024.114235
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.