Details

Autor(en) / Beteiligte

• Scheid, Johannes F.
• Barnes, Christopher O.
• Eraslan, Basak
• Hudak, Andrew
• Keeffe, Jennifer R.
• Cosimi, Lisa A.
• Brown, Eric M.
• Muecksch, Frauke
• Weisblum, Yiska
• Zhang, Shuting
• Delorey, Toni
• Woolley, Ann E.
• Ghantous, Fadi
• Park, Sung-Moo
• Phillips, Devan
• Tusi, Betsabeh
• Huey-Tubman, Kathryn E.
• Cohen, Alexander A.
• Gnanapragasam, Priyanthi N.P.
• Rzasa, Kara
• Hatziioanno, Theodora
• Durney, Michael A.
• Gu, Xiebin
• Tada, Takuya
• Landau, Nathaniel R.
• West, Anthony P.
• Rozenblatt-Rosen, Orit
• Seaman, Michael S.
• Baden, Lindsey R.
• Graham, Daniel B.
• Deguine, Jacques
• Bieniasz, Paul D.
• Regev, Aviv
• Hung, Deborah
• Bjorkman, Pamela J.
• Xavier, Ramnik J.

Titel

B cell genomics behind cross-neutralization of SARS-CoV-2 variants and SARS-CoV

Ist Teil von

• Cell, 2021-06, Vol.184 (12), p.3205-3221.e24

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •SARS-CoV-2-specific B cell repertoire includes transcriptionally distinct B cells•14 out of 15 potent neutralizers are from two clusters, memory and activated B cells•BG10-19 locks the spike trimer in a closed conformation to potently neutralize SARS-CoV-2•Several potent antibodies, including BG10-19, neutralize SARS-CoV-2 variants of concern B cell genomics reveals transcriptionally distinct populations that modulate antibody responses to SARS-CoV-2, with the identification of a monoclonal antibody that locks the virus spike trimer to neutralize recent variants, SARS and heterologous RBDs.