RT Journal Article
SR Electronic
T1 Bispecific antibody neutralizes circulating SARS-CoV-2 variants, prevents escape and protects mice from disease
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.01.22.427567
DO 10.1101/2021.01.22.427567
A1 Raoul De Gasparo
A1 Mattia Pedotti
A1 Luca Simonelli
A1 Petr Nickl
A1 Frauke Muecksch
A1 Irene Cassaniti
A1 Elena Percivalle
A1 Julio C. C. Lorenzi
A1 Federica Mazzola
A1 Davide Magrì
A1 Tereza Michalcikova
A1 Jan Haviernik
A1 Vaclav Honig
A1 Blanka Mrazkova
A1 Natalie Polakova
A1 Andrea Fortova
A1 Jolana Tureckova
A1 Veronika Iatsiuk
A1 Salvatore Di Girolamo
A1 Martin Palus
A1 Dagmar Zudova
A1 Petr Bednar
A1 Ivana Bukova
A1 Filippo Bianchini
A1 Dora Mehn
A1 Radim Nencka
A1 Petra Strakova
A1 Oto Pavlis
A1 Jan Rozman
A1 Sabrina Gioria
A1 Josè Camilla Sammartino
A1 Federica Giardina
A1 Stefano Gaiarsa
A1 Qiang Pan Hammarström
A1 Christopher O. Barnes
A1 Pamela J. Bjorkman
A1 Luigi Calzolai
A1 Antonio Piralla
A1 Fausto Baldanti
A1 Michel C. Nussenzweig
A1 Paul D. Bieniasz
A1 Theodora Hatziioannou
A1 Jan Prochazka
A1 Radislav Sedlacek
A1 Davide F. Robbiani
A1 Daniel Ruzek
A1 Luca Varani
YR 2021
UL http://biorxiv.org/content/early/2021/03/05/2021.01.22.427567.abstract
AB 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)1,2. We developed a bispecific, IgG1-like molecule (CoV-X2) based on two antibodies derived from COVID-19 convalescent donors, C121 and C1353. 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.Competing Interest StatementIn connection with this work the Institute for Research in Biomedicine has filed a provisional patent application on which L.V. is inventor (PCT/EP2020/085342). The Rockefeller University has filed a provisional patent application on which D.F.R. and M.C.N. are inventors.