tetano
Editor, Senior Moderator
Cell
. 2021 Apr 24;S0092-8674(21)00535-3.
doi: 10.1016/j.cell.2021.04.032. Online ahead of print.
B cell genomics behind cross-neutralization of SARS-CoV-2 variants and SARS-CoV
Johannes F Scheid[SUP] 1 [/SUP], Christopher O Barnes[SUP] 2 [/SUP], Basak Eraslan[SUP] 3 [/SUP], Andrew Hudak[SUP] 3 [/SUP], Jennifer R Keeffe[SUP] 2 [/SUP], Lisa A Cosimi[SUP] 4 [/SUP], Eric M Brown[SUP] 5 [/SUP], Frauke Muecksch[SUP] 6 [/SUP], Yiska Weisblum[SUP] 6 [/SUP], Shuting Zhang[SUP] 3 [/SUP], Toni Delorey[SUP] 7 [/SUP], Ann E Woolley[SUP] 4 [/SUP], Fadi Ghantous[SUP] 8 [/SUP], Sung-Moo Park[SUP] 3 [/SUP], Devan Phillips[SUP] 7 [/SUP], Betsabeh Tusi[SUP] 3 [/SUP], Kathryn E Huey-Tubman[SUP] 2 [/SUP], Alexander A Cohen[SUP] 2 [/SUP], Priyanthi N P Gnanapragasam[SUP] 2 [/SUP], Kara Rzasa[SUP] 3 [/SUP], Theodora Hatziioanno[SUP] 6 [/SUP], Michael A Durney[SUP] 3 [/SUP], Xiebin Gu[SUP] 3 [/SUP], Takuya Tada[SUP] 9 [/SUP], Nathaniel R Landau[SUP] 9 [/SUP], Anthony P West Jr[SUP] 2 [/SUP], Orit Rozenblatt-Rosen[SUP] 7 [/SUP], Michael S Seaman[SUP] 8 [/SUP], Lindsey R Baden[SUP] 4 [/SUP], Daniel B Graham[SUP] 5 [/SUP], Jacques Deguine[SUP] 3 [/SUP], Paul D Bieniasz[SUP] 10 [/SUP], Aviv Regev[SUP] 11 [/SUP], Deborah Hung[SUP] 12 [/SUP], Pamela J Bjorkman[SUP] 13 [/SUP], Ramnik J Xavier[SUP] 14 [/SUP]
Affiliations
Abstract
Monoclonal antibodies (mAbs) are a focus in vaccine and therapeutic design to counteract severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants. Here, we combined B cell sorting with single-cell VDJ and RNA sequencing (RNA-seq) and mAb structures to characterize B cell responses against SARS-CoV-2. We show that the SARS-CoV-2-specific B cell repertoire consists of transcriptionally distinct B cell populations with cells producing potently neutralizing antibodies (nAbs) localized in two clusters that resemble memory and activated B cells. Cryo-electron microscopy structures of selected nAbs from these two clusters complexed with SARS-CoV-2 spike trimers show recognition of various receptor-binding domain (RBD) epitopes. One of these mAbs, BG10-19, locks the spike trimer in a closed conformation to potently neutralize SARS-CoV-2, the recently arising mutants B.1.1.7 and B.1.351, and SARS-CoV and cross-reacts with heterologous RBDs. Together, our results characterize transcriptional differences among SARS-CoV-2-specific B cells and uncover cross-neutralizing Ab targets that will inform immunogen and therapeutic design against coronaviruses.
Keywords: COVID-19; SARS-CoV cross-neutralization; cryo-electron microscopy; disordered CDRH3; memory B cells; monoclonal antibodies; single B cell genomics.
. 2021 Apr 24;S0092-8674(21)00535-3.
doi: 10.1016/j.cell.2021.04.032. Online ahead of print.
B cell genomics behind cross-neutralization of SARS-CoV-2 variants and SARS-CoV
Johannes F Scheid[SUP] 1 [/SUP], Christopher O Barnes[SUP] 2 [/SUP], Basak Eraslan[SUP] 3 [/SUP], Andrew Hudak[SUP] 3 [/SUP], Jennifer R Keeffe[SUP] 2 [/SUP], Lisa A Cosimi[SUP] 4 [/SUP], Eric M Brown[SUP] 5 [/SUP], Frauke Muecksch[SUP] 6 [/SUP], Yiska Weisblum[SUP] 6 [/SUP], Shuting Zhang[SUP] 3 [/SUP], Toni Delorey[SUP] 7 [/SUP], Ann E Woolley[SUP] 4 [/SUP], Fadi Ghantous[SUP] 8 [/SUP], Sung-Moo Park[SUP] 3 [/SUP], Devan Phillips[SUP] 7 [/SUP], Betsabeh Tusi[SUP] 3 [/SUP], Kathryn E Huey-Tubman[SUP] 2 [/SUP], Alexander A Cohen[SUP] 2 [/SUP], Priyanthi N P Gnanapragasam[SUP] 2 [/SUP], Kara Rzasa[SUP] 3 [/SUP], Theodora Hatziioanno[SUP] 6 [/SUP], Michael A Durney[SUP] 3 [/SUP], Xiebin Gu[SUP] 3 [/SUP], Takuya Tada[SUP] 9 [/SUP], Nathaniel R Landau[SUP] 9 [/SUP], Anthony P West Jr[SUP] 2 [/SUP], Orit Rozenblatt-Rosen[SUP] 7 [/SUP], Michael S Seaman[SUP] 8 [/SUP], Lindsey R Baden[SUP] 4 [/SUP], Daniel B Graham[SUP] 5 [/SUP], Jacques Deguine[SUP] 3 [/SUP], Paul D Bieniasz[SUP] 10 [/SUP], Aviv Regev[SUP] 11 [/SUP], Deborah Hung[SUP] 12 [/SUP], Pamela J Bjorkman[SUP] 13 [/SUP], Ramnik J Xavier[SUP] 14 [/SUP]
Affiliations
- PMID: 34015271
- DOI: 10.1016/j.cell.2021.04.032
Abstract
Monoclonal antibodies (mAbs) are a focus in vaccine and therapeutic design to counteract severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants. Here, we combined B cell sorting with single-cell VDJ and RNA sequencing (RNA-seq) and mAb structures to characterize B cell responses against SARS-CoV-2. We show that the SARS-CoV-2-specific B cell repertoire consists of transcriptionally distinct B cell populations with cells producing potently neutralizing antibodies (nAbs) localized in two clusters that resemble memory and activated B cells. Cryo-electron microscopy structures of selected nAbs from these two clusters complexed with SARS-CoV-2 spike trimers show recognition of various receptor-binding domain (RBD) epitopes. One of these mAbs, BG10-19, locks the spike trimer in a closed conformation to potently neutralize SARS-CoV-2, the recently arising mutants B.1.1.7 and B.1.351, and SARS-CoV and cross-reacts with heterologous RBDs. Together, our results characterize transcriptional differences among SARS-CoV-2-specific B cells and uncover cross-neutralizing Ab targets that will inform immunogen and therapeutic design against coronaviruses.
Keywords: COVID-19; SARS-CoV cross-neutralization; cryo-electron microscopy; disordered CDRH3; memory B cells; monoclonal antibodies; single B cell genomics.