tetano
Editor, Senior Moderator
Science
. 2021 Aug 3;eabj3321.
doi: 10.1126/science.abj3321. Online ahead of print.
Broad betacoronavirus neutralization by a stem helix-specific human antibody
Dora Pinto[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Maximilian M Sauer[SUP] #[/SUP][SUP] 3 1 [/SUP], Nadine Czudnochowski[SUP] #[/SUP][SUP] 4 4 [/SUP], Jun Siong Low[SUP] #[/SUP][SUP] 5 6 5 [/SUP], M Alejandra Tortorici[SUP] 3 1 [/SUP], Michael P Housley[SUP] 4 4 [/SUP], Julia Noack[SUP] 4 4 [/SUP], Alexandra C Walls[SUP] 3 1 [/SUP], John E Bowen[SUP] 3 1 [/SUP], Barbara Guarino[SUP] 1 2 3 [/SUP], Laura E Rosen[SUP] 4 4 [/SUP], Julia di Iulio[SUP] 4 4 [/SUP], Josipa Jerak[SUP] 5 6 7 5 [/SUP], Hannah Kaiser[SUP] 4 4 [/SUP], Saiful Islam[SUP] 4 1 4 [/SUP], Stefano Jaconi[SUP] 1 2 3 [/SUP], Nicole Sprugasci[SUP] 1 2 3 [/SUP], Katja Culap[SUP] 1 2 3 [/SUP], Rana Abdelnabi[SUP] 8 2 [/SUP], Caroline Foo[SUP] 8 2 [/SUP], Lotte Coelmont[SUP] 8 2 [/SUP], Istvan Bartha[SUP] 1 2 3 [/SUP], Siro Bianchi[SUP] 1 2 3 [/SUP], Chiara Silacci-Fregni[SUP] 1 2 3 [/SUP], Jessica Bassi[SUP] 4 1 2 3 [/SUP], Roberta Marzi[SUP] 1 2 3 [/SUP], Eneida Vetti[SUP] 1 2 3 [/SUP], Antonino Cassotta[SUP] 5 6 5 [/SUP], Alessandro Ceschi[SUP] 5 9 10 8 9 11 12 [/SUP], Paolo Ferrari[SUP] 11 10 12 13 14 [/SUP], Pietro E Cippà[SUP] 11 10 13 15 [/SUP], Olivier Giannini[SUP] 5 12 13 [/SUP], Samuele Ceruti[SUP] 15 16 [/SUP], Christian Garzoni[SUP] 15 17 [/SUP], Agostino Riva[SUP] 18 [/SUP], Fabio Benigni[SUP] 1 2 3 [/SUP], Elisabetta Cameroni[SUP] 1 2 3 [/SUP], Luca Piccoli[SUP] 1 2 3 [/SUP], Matteo S Pizzuto[SUP] 1 2 3 [/SUP], Megan Smithey[SUP] 4 4 [/SUP], David Hong[SUP] 4 4 [/SUP], Amalio Telenti[SUP] 4 4 [/SUP], Florian A Lempp[SUP] 4 4 [/SUP], Johan Neyts[SUP] 8 2 [/SUP], Colin Havenar-Daughton[SUP] 4 4 [/SUP], Antonio Lanzavecchia[SUP] 1 2 3 [/SUP], Federica Sallusto[SUP] 5 5 10 [/SUP], Gyorgy Snell[SUP] 4 4 [/SUP], Herbert W Virgin[SUP] 4 16 18 4 7 6 [/SUP], Martina Beltramello[SUP] 1 3 [/SUP], Davide Corti[SUP] 19 2 3 [/SUP], David Veesler[SUP] 20 1 [/SUP]
Affiliations
Abstract
The spillovers of β-coronaviruses in humans and the emergence of SARS-CoV-2 variants highlight the need for broad coronavirus countermeasures. We describe five monoclonal antibodies (mAbs) cross-reacting with the stem helix of multiple β-coronavirus spike glycoproteins isolated from COVID-19 convalescent individuals. Using structural and functional studies we show that the mAb with the greatest breadth (S2P6) neutralizes pseudotyped viruses from three different subgenera through inhibition of membrane fusion and delineate the molecular basis for its cross-reactivity. S2P6 reduces viral burden in hamsters challenged with SARS-CoV-2 through viral neutralization and Fc-mediated effector functions. Stem helix antibodies are rare, oftentimes of narrow specificity and can acquire neutralization breadth through somatic mutations. These data provide a framework for structure-guided design of pan-β-coronavirus vaccines eliciting broad protection.
. 2021 Aug 3;eabj3321.
doi: 10.1126/science.abj3321. Online ahead of print.
Broad betacoronavirus neutralization by a stem helix-specific human antibody
Dora Pinto[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Maximilian M Sauer[SUP] #[/SUP][SUP] 3 1 [/SUP], Nadine Czudnochowski[SUP] #[/SUP][SUP] 4 4 [/SUP], Jun Siong Low[SUP] #[/SUP][SUP] 5 6 5 [/SUP], M Alejandra Tortorici[SUP] 3 1 [/SUP], Michael P Housley[SUP] 4 4 [/SUP], Julia Noack[SUP] 4 4 [/SUP], Alexandra C Walls[SUP] 3 1 [/SUP], John E Bowen[SUP] 3 1 [/SUP], Barbara Guarino[SUP] 1 2 3 [/SUP], Laura E Rosen[SUP] 4 4 [/SUP], Julia di Iulio[SUP] 4 4 [/SUP], Josipa Jerak[SUP] 5 6 7 5 [/SUP], Hannah Kaiser[SUP] 4 4 [/SUP], Saiful Islam[SUP] 4 1 4 [/SUP], Stefano Jaconi[SUP] 1 2 3 [/SUP], Nicole Sprugasci[SUP] 1 2 3 [/SUP], Katja Culap[SUP] 1 2 3 [/SUP], Rana Abdelnabi[SUP] 8 2 [/SUP], Caroline Foo[SUP] 8 2 [/SUP], Lotte Coelmont[SUP] 8 2 [/SUP], Istvan Bartha[SUP] 1 2 3 [/SUP], Siro Bianchi[SUP] 1 2 3 [/SUP], Chiara Silacci-Fregni[SUP] 1 2 3 [/SUP], Jessica Bassi[SUP] 4 1 2 3 [/SUP], Roberta Marzi[SUP] 1 2 3 [/SUP], Eneida Vetti[SUP] 1 2 3 [/SUP], Antonino Cassotta[SUP] 5 6 5 [/SUP], Alessandro Ceschi[SUP] 5 9 10 8 9 11 12 [/SUP], Paolo Ferrari[SUP] 11 10 12 13 14 [/SUP], Pietro E Cippà[SUP] 11 10 13 15 [/SUP], Olivier Giannini[SUP] 5 12 13 [/SUP], Samuele Ceruti[SUP] 15 16 [/SUP], Christian Garzoni[SUP] 15 17 [/SUP], Agostino Riva[SUP] 18 [/SUP], Fabio Benigni[SUP] 1 2 3 [/SUP], Elisabetta Cameroni[SUP] 1 2 3 [/SUP], Luca Piccoli[SUP] 1 2 3 [/SUP], Matteo S Pizzuto[SUP] 1 2 3 [/SUP], Megan Smithey[SUP] 4 4 [/SUP], David Hong[SUP] 4 4 [/SUP], Amalio Telenti[SUP] 4 4 [/SUP], Florian A Lempp[SUP] 4 4 [/SUP], Johan Neyts[SUP] 8 2 [/SUP], Colin Havenar-Daughton[SUP] 4 4 [/SUP], Antonio Lanzavecchia[SUP] 1 2 3 [/SUP], Federica Sallusto[SUP] 5 5 10 [/SUP], Gyorgy Snell[SUP] 4 4 [/SUP], Herbert W Virgin[SUP] 4 16 18 4 7 6 [/SUP], Martina Beltramello[SUP] 1 3 [/SUP], Davide Corti[SUP] 19 2 3 [/SUP], David Veesler[SUP] 20 1 [/SUP]
Affiliations
- PMID: 34344823
- DOI: 10.1126/science.abj3321
Abstract
The spillovers of β-coronaviruses in humans and the emergence of SARS-CoV-2 variants highlight the need for broad coronavirus countermeasures. We describe five monoclonal antibodies (mAbs) cross-reacting with the stem helix of multiple β-coronavirus spike glycoproteins isolated from COVID-19 convalescent individuals. Using structural and functional studies we show that the mAb with the greatest breadth (S2P6) neutralizes pseudotyped viruses from three different subgenera through inhibition of membrane fusion and delineate the molecular basis for its cross-reactivity. S2P6 reduces viral burden in hamsters challenged with SARS-CoV-2 through viral neutralization and Fc-mediated effector functions. Stem helix antibodies are rare, oftentimes of narrow specificity and can acquire neutralization breadth through somatic mutations. These data provide a framework for structure-guided design of pan-β-coronavirus vaccines eliciting broad protection.