tetano
Editor, Senior Moderator
Nature
. 2021 Dec 23.
doi: 10.1038/s41586-021-04386-2. Online ahead of print.
Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift
Elisabetta Cameroni[SUP] #[/SUP][SUP] 1 [/SUP], John E Bowen[SUP] #[/SUP][SUP] 2 [/SUP], Laura E Rosen[SUP] #[/SUP][SUP] 3 [/SUP], Christian Saliba[SUP] #[/SUP][SUP] 1 [/SUP], Samantha K Zepeda[SUP] 2 [/SUP], Katja Culap[SUP] 1 [/SUP], Dora Pinto[SUP] 1 [/SUP], Laura A VanBlargan[SUP] 4 [/SUP], Anna De Marco[SUP] 1 [/SUP], Julia di Iulio[SUP] 3 [/SUP], Fabrizia Zatta[SUP] 1 [/SUP], Hannah Kaiser[SUP] 3 [/SUP], Julia Noack[SUP] 3 [/SUP], Nisar Farhat[SUP] 3 [/SUP], Nadine Czudnochowski[SUP] 3 [/SUP], Colin Havenar-Daughton[SUP] 3 [/SUP], Kaitlin R Sprouse[SUP] 2 [/SUP], Josh R Dillen[SUP] 3 [/SUP], Abigail E Powell[SUP] 3 [/SUP], Alex Chen[SUP] 3 [/SUP], Cyrus Maher[SUP] 3 [/SUP], Li Yin[SUP] 3 [/SUP], David Sun[SUP] 3 [/SUP], Leah Soriaga[SUP] 3 [/SUP], Jessica Bassi[SUP] 1 [/SUP], Chiara Silacci-Fregni[SUP] 1 [/SUP], Claes Gustafsson[SUP] 5 [/SUP], Nicholas M Franko[SUP] 6 [/SUP], Jenni Logue[SUP] 6 [/SUP], Najeeha Talat Iqbal[SUP] 7 [/SUP], Ignacio Mazzitelli[SUP] 8 [/SUP], Jorge Geffner[SUP] 8 [/SUP], Renata Grifantini[SUP] 9 [/SUP], Helen Chu[SUP] 6 [/SUP], Andrea Gori[SUP] 10 [/SUP], Agostino Riva[SUP] 11 [/SUP], Olivier Giannini[SUP] 12 13 [/SUP], Alessandro Ceschi[SUP] 12 14 15 16 [/SUP], Paolo Ferrari[SUP] 12 17 18 [/SUP], Pietro E Cippà[SUP] 13 17 19 [/SUP], Alessandra Franzetti-Pellanda[SUP] 20 [/SUP], Christian Garzoni[SUP] 21 [/SUP], Peter J Halfmann[SUP] 22 [/SUP], Yoshihiro Kawaoka[SUP] 22 23 24 [/SUP], Christy Hebner[SUP] 3 [/SUP], Lisa A Purcell[SUP] 3 [/SUP], Luca Piccoli[SUP] 1 [/SUP], Matteo Samuele Pizzuto[SUP] 1 [/SUP], Alexandra C Walls[SUP] 2 25 [/SUP], Michael S Diamond[SUP] 4 26 27 [/SUP], Amalio Telenti[SUP] 3 [/SUP], Herbert W Virgin[SUP] 3 26 28 [/SUP], Antonio Lanzavecchia[SUP] 1 9 [/SUP], Gyorgy Snell[SUP] 29 [/SUP], David Veesler[SUP] 30 31 [/SUP], Davide Corti[SUP] 32 [/SUP]
Affiliations
Abstract
The recently emerged SARS-CoV-2 Omicron variant encodes 37 amino acid substitutions in the spike (S) protein, 15 of which are in the receptor-binding domain (RBD), thereby raising concerns about the effectiveness of available vaccines and antibody therapeutics. Here, we show that the Omicron RBD binds to human ACE2 with enhanced affinity, relative to the Wuhan-Hu-1 RBD, and binds to mouse ACE2. Marked reductions of plasma neutralizing activity were observed against Omicron compared to the ancestral pseudovirus for convalescent and vaccinated individuals, but this loss was less pronounced after a third vaccine dose. Most receptor-binding motif (RBM)-directed monoclonal antibodies (mAbs) lost in vitro neutralizing activity against Omicron, with only 3 out of 29 mAbs retaining unaltered potency, including the ACE2-mimicking S2K146 mAb[SUP]1[/SUP]. Furthermore, a fraction of broadly neutralizing sarbecovirus mAbs neutralized Omicron through recognition of antigenic sites outside the RBM, including sotrovimab[SUP]2[/SUP], S2X259[SUP]3[/SUP] and S2H97[SUP]4[/SUP]. The magnitude of Omicron-mediated immune evasion marks a major SARS-CoV-2 antigenic shift. Broadly neutralizing mAbs recognizing RBD epitopes conserved among SARS-CoV-2 variants and other sarbecoviruses may prove key to controlling the ongoing pandemic and future zoonotic spillovers.
. 2021 Dec 23.
doi: 10.1038/s41586-021-04386-2. Online ahead of print.
Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift
Elisabetta Cameroni[SUP] #[/SUP][SUP] 1 [/SUP], John E Bowen[SUP] #[/SUP][SUP] 2 [/SUP], Laura E Rosen[SUP] #[/SUP][SUP] 3 [/SUP], Christian Saliba[SUP] #[/SUP][SUP] 1 [/SUP], Samantha K Zepeda[SUP] 2 [/SUP], Katja Culap[SUP] 1 [/SUP], Dora Pinto[SUP] 1 [/SUP], Laura A VanBlargan[SUP] 4 [/SUP], Anna De Marco[SUP] 1 [/SUP], Julia di Iulio[SUP] 3 [/SUP], Fabrizia Zatta[SUP] 1 [/SUP], Hannah Kaiser[SUP] 3 [/SUP], Julia Noack[SUP] 3 [/SUP], Nisar Farhat[SUP] 3 [/SUP], Nadine Czudnochowski[SUP] 3 [/SUP], Colin Havenar-Daughton[SUP] 3 [/SUP], Kaitlin R Sprouse[SUP] 2 [/SUP], Josh R Dillen[SUP] 3 [/SUP], Abigail E Powell[SUP] 3 [/SUP], Alex Chen[SUP] 3 [/SUP], Cyrus Maher[SUP] 3 [/SUP], Li Yin[SUP] 3 [/SUP], David Sun[SUP] 3 [/SUP], Leah Soriaga[SUP] 3 [/SUP], Jessica Bassi[SUP] 1 [/SUP], Chiara Silacci-Fregni[SUP] 1 [/SUP], Claes Gustafsson[SUP] 5 [/SUP], Nicholas M Franko[SUP] 6 [/SUP], Jenni Logue[SUP] 6 [/SUP], Najeeha Talat Iqbal[SUP] 7 [/SUP], Ignacio Mazzitelli[SUP] 8 [/SUP], Jorge Geffner[SUP] 8 [/SUP], Renata Grifantini[SUP] 9 [/SUP], Helen Chu[SUP] 6 [/SUP], Andrea Gori[SUP] 10 [/SUP], Agostino Riva[SUP] 11 [/SUP], Olivier Giannini[SUP] 12 13 [/SUP], Alessandro Ceschi[SUP] 12 14 15 16 [/SUP], Paolo Ferrari[SUP] 12 17 18 [/SUP], Pietro E Cippà[SUP] 13 17 19 [/SUP], Alessandra Franzetti-Pellanda[SUP] 20 [/SUP], Christian Garzoni[SUP] 21 [/SUP], Peter J Halfmann[SUP] 22 [/SUP], Yoshihiro Kawaoka[SUP] 22 23 24 [/SUP], Christy Hebner[SUP] 3 [/SUP], Lisa A Purcell[SUP] 3 [/SUP], Luca Piccoli[SUP] 1 [/SUP], Matteo Samuele Pizzuto[SUP] 1 [/SUP], Alexandra C Walls[SUP] 2 25 [/SUP], Michael S Diamond[SUP] 4 26 27 [/SUP], Amalio Telenti[SUP] 3 [/SUP], Herbert W Virgin[SUP] 3 26 28 [/SUP], Antonio Lanzavecchia[SUP] 1 9 [/SUP], Gyorgy Snell[SUP] 29 [/SUP], David Veesler[SUP] 30 31 [/SUP], Davide Corti[SUP] 32 [/SUP]
Affiliations
- PMID: 35016195
- DOI: 10.1038/s41586-021-04386-2
Abstract
The recently emerged SARS-CoV-2 Omicron variant encodes 37 amino acid substitutions in the spike (S) protein, 15 of which are in the receptor-binding domain (RBD), thereby raising concerns about the effectiveness of available vaccines and antibody therapeutics. Here, we show that the Omicron RBD binds to human ACE2 with enhanced affinity, relative to the Wuhan-Hu-1 RBD, and binds to mouse ACE2. Marked reductions of plasma neutralizing activity were observed against Omicron compared to the ancestral pseudovirus for convalescent and vaccinated individuals, but this loss was less pronounced after a third vaccine dose. Most receptor-binding motif (RBM)-directed monoclonal antibodies (mAbs) lost in vitro neutralizing activity against Omicron, with only 3 out of 29 mAbs retaining unaltered potency, including the ACE2-mimicking S2K146 mAb[SUP]1[/SUP]. Furthermore, a fraction of broadly neutralizing sarbecovirus mAbs neutralized Omicron through recognition of antigenic sites outside the RBM, including sotrovimab[SUP]2[/SUP], S2X259[SUP]3[/SUP] and S2H97[SUP]4[/SUP]. The magnitude of Omicron-mediated immune evasion marks a major SARS-CoV-2 antigenic shift. Broadly neutralizing mAbs recognizing RBD epitopes conserved among SARS-CoV-2 variants and other sarbecoviruses may prove key to controlling the ongoing pandemic and future zoonotic spillovers.
