tetano
Editor, Senior Moderator
Nature
. 2021 Mar 25.
doi: 10.1038/s41586-021-03461-y. Online ahead of print.
Bispecific IgG neutralizes SARS-CoV-2 variants and prevents escape in mice
Raoul De Gasparo[SUP] #[/SUP][SUP] 1 [/SUP], Mattia Pedotti[SUP] #[/SUP][SUP] 1 [/SUP], Luca Simonelli[SUP] 1 [/SUP], Petr Nickl[SUP] 2 [/SUP], Frauke Muecksch[SUP] 3 [/SUP], Irene Cassaniti[SUP] 4 [/SUP], Elena Percivalle[SUP] 4 [/SUP], Julio C C Lorenzi[SUP] 5 [/SUP], Federica Mazzola[SUP] 1 [/SUP], Davide Magr?[SUP] 6 [/SUP], Tereza Michalcikova[SUP] 2 [/SUP], Jan Haviernik[SUP] 7 [/SUP], Vaclav Honig[SUP] 7 8 [/SUP], Blanka Mrazkova[SUP] 2 [/SUP], Natalie Polakova[SUP] 2 [/SUP], Andrea Fortova[SUP] 7 [/SUP], Jolana Tureckova[SUP] 2 [/SUP], Veronika Iatsiuk[SUP] 2 [/SUP], Salvatore Di Girolamo[SUP] 1 [/SUP], Martin Palus[SUP] 7 8 [/SUP], Dagmar Zudova[SUP] 2 [/SUP], Petr Bednar[SUP] 7 9 [/SUP], Ivana Bukova[SUP] 2 [/SUP], Filippo Bianchini[SUP] 1 [/SUP], Dora Mehn[SUP] 6 [/SUP], Radim Nencka[SUP] 10 [/SUP], Petra Strakova[SUP] 7 [/SUP], Oto Pavlis[SUP] 11 [/SUP], Jan Rozman[SUP] 2 [/SUP], Sabrina Gioria[SUP] 6 [/SUP], Jos? Camilla Sammartino[SUP] 4 [/SUP], Federica Giardina[SUP] 4 [/SUP], Stefano Gaiarsa[SUP] 4 [/SUP], Qiang Pan-Hammarstr?m[SUP] 12 [/SUP], Christopher O Barnes[SUP] 13 [/SUP], Pamela J Bjorkman[SUP] 13 [/SUP], Luigi Calzolai[SUP] 6 [/SUP], Antonio Piralla[SUP] 4 [/SUP], Fausto Baldanti[SUP] 4 [/SUP], Michel C Nussenzweig[SUP] 5 14 [/SUP], Paul D Bieniasz[SUP] 3 14 [/SUP], Theodora Hatziioannou[SUP] 3 [/SUP], Jan Prochazka[SUP] 2 [/SUP], Radislav Sedlacek[SUP] 2 [/SUP], Davide F Robbiani[SUP] 15 [/SUP], Daniel Ruzek[SUP] 16 17 [/SUP], Luca Varani[SUP] 18 [/SUP]
Affiliations
Abstract
Neutralizing antibodies targeting the receptor binding domain (RBD) of the SARS-CoV-2 Spike (S) are among the most promising approaches against coronavirus disease 2019 (COVID-19)[SUP]1,2[/SUP]. We developed a bispecific, IgG1-like molecule (CoV-X2) based on two antibodies derived from COVID-19 convalescent donors, C121 and C135[SUP]3[/SUP]. CoV-X2 simultaneously binds two independent sites on the RBD and, unlike its parental antibodies, prevents detectable S binding to Angiotensin-Converting Enzyme 2 (ACE2), the virus cellular receptor. Furthermore, CoV-X2 neutralizes SARS-CoV-2 and its variants of concern, as well as the escape mutants generated by the parental monoclonals. In a novel animal model of SARS-CoV-2 infection with lung inflammation, CoV-X2 protects mice from disease and suppresses viral escape. Thus, simultaneous targeting of non-overlapping RBD epitopes by IgG-like bispecific antibodies is feasible and effective, combining into a single molecule the advantages of antibody cocktails.
. 2021 Mar 25.
doi: 10.1038/s41586-021-03461-y. Online ahead of print.
Bispecific IgG neutralizes SARS-CoV-2 variants and prevents escape in mice
Raoul De Gasparo[SUP] #[/SUP][SUP] 1 [/SUP], Mattia Pedotti[SUP] #[/SUP][SUP] 1 [/SUP], Luca Simonelli[SUP] 1 [/SUP], Petr Nickl[SUP] 2 [/SUP], Frauke Muecksch[SUP] 3 [/SUP], Irene Cassaniti[SUP] 4 [/SUP], Elena Percivalle[SUP] 4 [/SUP], Julio C C Lorenzi[SUP] 5 [/SUP], Federica Mazzola[SUP] 1 [/SUP], Davide Magr?[SUP] 6 [/SUP], Tereza Michalcikova[SUP] 2 [/SUP], Jan Haviernik[SUP] 7 [/SUP], Vaclav Honig[SUP] 7 8 [/SUP], Blanka Mrazkova[SUP] 2 [/SUP], Natalie Polakova[SUP] 2 [/SUP], Andrea Fortova[SUP] 7 [/SUP], Jolana Tureckova[SUP] 2 [/SUP], Veronika Iatsiuk[SUP] 2 [/SUP], Salvatore Di Girolamo[SUP] 1 [/SUP], Martin Palus[SUP] 7 8 [/SUP], Dagmar Zudova[SUP] 2 [/SUP], Petr Bednar[SUP] 7 9 [/SUP], Ivana Bukova[SUP] 2 [/SUP], Filippo Bianchini[SUP] 1 [/SUP], Dora Mehn[SUP] 6 [/SUP], Radim Nencka[SUP] 10 [/SUP], Petra Strakova[SUP] 7 [/SUP], Oto Pavlis[SUP] 11 [/SUP], Jan Rozman[SUP] 2 [/SUP], Sabrina Gioria[SUP] 6 [/SUP], Jos? Camilla Sammartino[SUP] 4 [/SUP], Federica Giardina[SUP] 4 [/SUP], Stefano Gaiarsa[SUP] 4 [/SUP], Qiang Pan-Hammarstr?m[SUP] 12 [/SUP], Christopher O Barnes[SUP] 13 [/SUP], Pamela J Bjorkman[SUP] 13 [/SUP], Luigi Calzolai[SUP] 6 [/SUP], Antonio Piralla[SUP] 4 [/SUP], Fausto Baldanti[SUP] 4 [/SUP], Michel C Nussenzweig[SUP] 5 14 [/SUP], Paul D Bieniasz[SUP] 3 14 [/SUP], Theodora Hatziioannou[SUP] 3 [/SUP], Jan Prochazka[SUP] 2 [/SUP], Radislav Sedlacek[SUP] 2 [/SUP], Davide F Robbiani[SUP] 15 [/SUP], Daniel Ruzek[SUP] 16 17 [/SUP], Luca Varani[SUP] 18 [/SUP]
Affiliations
- PMID: 33767445
- DOI: 10.1038/s41586-021-03461-y
Abstract
Neutralizing antibodies targeting the receptor binding domain (RBD) of the SARS-CoV-2 Spike (S) are among the most promising approaches against coronavirus disease 2019 (COVID-19)[SUP]1,2[/SUP]. We developed a bispecific, IgG1-like molecule (CoV-X2) based on two antibodies derived from COVID-19 convalescent donors, C121 and C135[SUP]3[/SUP]. CoV-X2 simultaneously binds two independent sites on the RBD and, unlike its parental antibodies, prevents detectable S binding to Angiotensin-Converting Enzyme 2 (ACE2), the virus cellular receptor. Furthermore, CoV-X2 neutralizes SARS-CoV-2 and its variants of concern, as well as the escape mutants generated by the parental monoclonals. In a novel animal model of SARS-CoV-2 infection with lung inflammation, CoV-X2 protects mice from disease and suppresses viral escape. Thus, simultaneous targeting of non-overlapping RBD epitopes by IgG-like bispecific antibodies is feasible and effective, combining into a single molecule the advantages of antibody cocktails.