Bispecific antibody prevents SARS-CoV-2 escape and protects mice from disease
Raoul De Gasparo; Mattia Pedotti; Luca Simonelli; Petr Nickl; Frauke Muecksch; Irene Cassaniti; Elena Percivalle; Julio C. C. Lorenzi; Federica Mazzola; Davide Magrì; Tereza Michalcikova; Jan Haviernik; Vaclav Honig; Blanka Mrazkova; Natalie Polakova; Andrea Fortova; Jolana Tureckova; Veronika Iatsiuk; Salvatore Di Girolamo; Martin Palus; Dagmar Zudova; Petr Bednar; Ivana Bukova; Filippo Bianchini; Dora Mehn; Radim Nencka; Petra Strakova; Oto Pavlis; Jan Rozman; Sabrina Gioria; Josè Camilla Sammartino; Federica Giardina; Stefano Gaiarsa; Qiang Pan Hammarström; Christopher O. Barnes; Pamela J. Bjorkman; Luigi Calzolai; Antonio Piralla; Fausto Baldanti; Michel C. Nussenzweig; Paul D. Bieniasz; Theodora Hatziioannou; Jan Prochazka; Radislav Sedlacek; Davide F. Robbiani; Daniel Ruzek; Luca Varani.
Preprint
en Inglés
| PREPRINT-BIORXIV | ID: ppbiorxiv-427567
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.
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