Bispecific antibody prevents SARS-CoV-2 escape and protects mice from disease

Researchers from the Czech Centre for Phenogenomics contributed to the paper “Bispecific antibody prevents SARS-CoV-2 escape and protects mice from disease“

Raoul De Gasparo, Mattia Pedotti, Luca Simonelli, Petr Nickl, Frauke Muecksch, Julio C. C. Lorenzi, Federica Mazzola, Davide Magrì, Tereza Michalcikova, Jan Haviernik, Vaclav Honig, Irene Cassaniti, Elena Percivalle, 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, Antonio Piralla, Pamela J. Bjorkman, Fausto Baldanti, Luigi Calzolai, Michel C. Nussenzweig, Paul D. Bieniasz, Theodora Hatziioannou, Jan Prochazka, Radislav Sedlacek, Davide F. Robbiani, Daniel Ruzek, Luca Varani
doi: https://doi.org/10.1101/2021.01.22.427567

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). We developed a bispecific, IgG1-like molecule based on two antibodies derived from COVID-19 convalescent donors, C121 and C135. CoV-X2 simultaneously binds two independent sites on the RBD and, unlike its parental antibodies, completely prevents S binding to Angiotensin-Converting Enzyme 2 (ACE2), the virus cellular receptor. Furthermore, CoV-X2 recognizes a broad panel of RBD variants and neutralizes SARS-CoV-2 and the escape mutants generated by the single monoclonals at sub-nanomolar concentrations. In a novel 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.