tetano
Editor, Senior Moderator
Cell
. 2024 Oct 4:S0092-8674(24)01084-5.
doi: 10.1016/j.cell.2024.09.026. Online ahead of print. A potent pan-sarbecovirus neutralizing antibody resilient to epitope diversification
Laura E Rosen[SUP] 1 [/SUP], M Alejandra Tortorici[SUP] 2 [/SUP], Anna De Marco[SUP] 3 [/SUP], Dora Pinto[SUP] 3 [/SUP], William B Foreman[SUP] 4 [/SUP], Ashley L Taylor[SUP] 4 [/SUP], Young-Jun Park[SUP] 5 [/SUP], Dana Bohan[SUP] 1 [/SUP], Tyson Rietz[SUP] 1 [/SUP], John M Errico[SUP] 1 [/SUP], Kevin Hauser[SUP] 1 [/SUP], Ha V Dang[SUP] 1 [/SUP], Justin W Chartron[SUP] 6 [/SUP], Martina Giurdanella[SUP] 3 [/SUP], Giuseppe Cusumano[SUP] 3 [/SUP], Christian Saliba[SUP] 3 [/SUP], Fabrizia Zatta[SUP] 3 [/SUP], Kaitlin R Sprouse[SUP] 2 [/SUP], Amin Addetia[SUP] 2 [/SUP], Samantha K Zepeda[SUP] 2 [/SUP], Jack Brown[SUP] 2 [/SUP], Jimin Lee[SUP] 2 [/SUP], Exequiel Dellota Jr[SUP] 1 [/SUP], Anushka Rajesh[SUP] 1 [/SUP], Julia Noack[SUP] 1 [/SUP], Qiqing Tao[SUP] 1 [/SUP], Yvonne DaCosta[SUP] 1 [/SUP], Brian Tsu[SUP] 1 [/SUP], Rima Acosta[SUP] 1 [/SUP], Sambhavi Subramanian[SUP] 1 [/SUP], Guilherme Dias de Melo[SUP] 7 [/SUP], Lauriane Kergoat[SUP] 7 [/SUP], Ivy Zhang[SUP] 8 [/SUP], Zhuoming Liu[SUP] 9 [/SUP], Barbara Guarino[SUP] 3 [/SUP], Michael A Schmid[SUP] 3 [/SUP], Gretja Schnell[SUP] 1 [/SUP], Jessica L Miller[SUP] 1 [/SUP], Florian A Lempp[SUP] 10 [/SUP], Nadine Czudnochowski[SUP] 1 [/SUP], Elisabetta Cameroni[SUP] 3 [/SUP], Sean P J Whelan[SUP] 9 [/SUP], Hervé Bourhy[SUP] 7 [/SUP], Lisa A Purcell[SUP] 1 [/SUP], Fabio Benigni[SUP] 3 [/SUP], Julia di Iulio[SUP] 1 [/SUP], Matteo Samuele Pizzuto[SUP] 3 [/SUP], Antonio Lanzavecchia[SUP] 3 [/SUP], Amalio Telenti[SUP] 1 [/SUP], Gyorgy Snell[SUP] 1 [/SUP], Davide Corti[SUP] 11 [/SUP], David Veesler[SUP] 12 [/SUP], Tyler N Starr[SUP] 13 [/SUP]
Affiliations
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution has resulted in viral escape from clinically authorized monoclonal antibodies (mAbs), creating a need for mAbs that are resilient to epitope diversification. Broadly neutralizing coronavirus mAbs that are sufficiently potent for clinical development and retain activity despite viral evolution remain elusive. We identified a human mAb, designated VIR-7229, which targets the viral receptor-binding motif (RBM) with unprecedented cross-reactivity to all sarbecovirus clades, including non-ACE2-utilizing bat sarbecoviruses, while potently neutralizing SARS-CoV-2 variants since 2019, including the recent EG.5, BA.2.86, and JN.1. VIR-7229 tolerates extraordinary epitope variability, partly attributed to its high binding affinity, receptor molecular mimicry, and interactions with RBM backbone atoms. Consequently, VIR-7229 features a high barrier for selection of escape mutants, which are rare and associated with reduced viral fitness, underscoring its potential to be resilient to future viral evolution. VIR-7229 is a strong candidate to become a next-generation medicine.
Keywords: SARS-CoV-2; broadly neutralizing antibody; monoclonal antibody; sarbecovirus; viral antibody escape.
. 2024 Oct 4:S0092-8674(24)01084-5.
doi: 10.1016/j.cell.2024.09.026. Online ahead of print. A potent pan-sarbecovirus neutralizing antibody resilient to epitope diversification
Laura E Rosen[SUP] 1 [/SUP], M Alejandra Tortorici[SUP] 2 [/SUP], Anna De Marco[SUP] 3 [/SUP], Dora Pinto[SUP] 3 [/SUP], William B Foreman[SUP] 4 [/SUP], Ashley L Taylor[SUP] 4 [/SUP], Young-Jun Park[SUP] 5 [/SUP], Dana Bohan[SUP] 1 [/SUP], Tyson Rietz[SUP] 1 [/SUP], John M Errico[SUP] 1 [/SUP], Kevin Hauser[SUP] 1 [/SUP], Ha V Dang[SUP] 1 [/SUP], Justin W Chartron[SUP] 6 [/SUP], Martina Giurdanella[SUP] 3 [/SUP], Giuseppe Cusumano[SUP] 3 [/SUP], Christian Saliba[SUP] 3 [/SUP], Fabrizia Zatta[SUP] 3 [/SUP], Kaitlin R Sprouse[SUP] 2 [/SUP], Amin Addetia[SUP] 2 [/SUP], Samantha K Zepeda[SUP] 2 [/SUP], Jack Brown[SUP] 2 [/SUP], Jimin Lee[SUP] 2 [/SUP], Exequiel Dellota Jr[SUP] 1 [/SUP], Anushka Rajesh[SUP] 1 [/SUP], Julia Noack[SUP] 1 [/SUP], Qiqing Tao[SUP] 1 [/SUP], Yvonne DaCosta[SUP] 1 [/SUP], Brian Tsu[SUP] 1 [/SUP], Rima Acosta[SUP] 1 [/SUP], Sambhavi Subramanian[SUP] 1 [/SUP], Guilherme Dias de Melo[SUP] 7 [/SUP], Lauriane Kergoat[SUP] 7 [/SUP], Ivy Zhang[SUP] 8 [/SUP], Zhuoming Liu[SUP] 9 [/SUP], Barbara Guarino[SUP] 3 [/SUP], Michael A Schmid[SUP] 3 [/SUP], Gretja Schnell[SUP] 1 [/SUP], Jessica L Miller[SUP] 1 [/SUP], Florian A Lempp[SUP] 10 [/SUP], Nadine Czudnochowski[SUP] 1 [/SUP], Elisabetta Cameroni[SUP] 3 [/SUP], Sean P J Whelan[SUP] 9 [/SUP], Hervé Bourhy[SUP] 7 [/SUP], Lisa A Purcell[SUP] 1 [/SUP], Fabio Benigni[SUP] 3 [/SUP], Julia di Iulio[SUP] 1 [/SUP], Matteo Samuele Pizzuto[SUP] 3 [/SUP], Antonio Lanzavecchia[SUP] 3 [/SUP], Amalio Telenti[SUP] 1 [/SUP], Gyorgy Snell[SUP] 1 [/SUP], Davide Corti[SUP] 11 [/SUP], David Veesler[SUP] 12 [/SUP], Tyler N Starr[SUP] 13 [/SUP]
Affiliations
- PMID: 39383863
- DOI: 10.1016/j.cell.2024.09.026
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution has resulted in viral escape from clinically authorized monoclonal antibodies (mAbs), creating a need for mAbs that are resilient to epitope diversification. Broadly neutralizing coronavirus mAbs that are sufficiently potent for clinical development and retain activity despite viral evolution remain elusive. We identified a human mAb, designated VIR-7229, which targets the viral receptor-binding motif (RBM) with unprecedented cross-reactivity to all sarbecovirus clades, including non-ACE2-utilizing bat sarbecoviruses, while potently neutralizing SARS-CoV-2 variants since 2019, including the recent EG.5, BA.2.86, and JN.1. VIR-7229 tolerates extraordinary epitope variability, partly attributed to its high binding affinity, receptor molecular mimicry, and interactions with RBM backbone atoms. Consequently, VIR-7229 features a high barrier for selection of escape mutants, which are rare and associated with reduced viral fitness, underscoring its potential to be resilient to future viral evolution. VIR-7229 is a strong candidate to become a next-generation medicine.
Keywords: SARS-CoV-2; broadly neutralizing antibody; monoclonal antibody; sarbecovirus; viral antibody escape.