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Bispecific antibody neutralizes circulating SARS-CoV-2 variants, prevents escape and protects mice from disease. 2021
Raoul De Gasparo, and
Mattia Pedotti, and
Luca Simonelli, and
Petr Nickl, and
Frauke Muecksch, and
Irene Cassaniti, and
Elena Percivalle, and
Julio C C Lorenzi, and
Federica Mazzola, and
Davide Magrì, and
Tereza Michalcikova, and
Jan Haviernik, and
Vaclav Honig, and
Blanka Mrazkova, and
Natalie Polakova, and
Andrea Fortova, and
Jolana Tureckova, and
Veronika Iatsiuk, and
Salvatore Di Girolamo, and
Martin Palus, and
Dagmar Zudova, and
Petr Bednar, and
Ivana Bukova, and
Filippo Bianchini, and
Dora Mehn, and
Radim Nencka, and
Petra Strakova, and
Oto Pavlis, and
Jan Rozman, and
Sabrina Gioria, and
Josè Camilla Sammartino, and
Federica Giardina, and
Stefano Gaiarsa, and
Qiang Pan Hammarström, and
Christopher O Barnes, and
Pamela J Bjorkman, and
Luigi Calzolai, and
Antonio Piralla, and
Fausto Baldanti, and
Michel C Nussenzweig, and
Paul D Bieniasz, and
Theodora Hatziioannou, and
Jan Prochazka, and
Radislav Sedlacek, and
Davide F Robbiani, and
Daniel Ruzek, and
Luca Varani
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 C135 3 . 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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Federica Giardina, and
Stefano Gaiarsa, and
Qiang Pan Hammarström, and
Christopher O Barnes, and
Pamela J Bjorkman, and
Luigi Calzolai, and
Antonio Piralla, and
Fausto Baldanti, and
Michel C Nussenzweig, and
Paul D Bieniasz, and
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