1. Bispecific IgG neutralizes SARS-CoV-2 variants and prevents escape in mice
- Author
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Luigi Calzolai, Federica Mazzola, Jan Haviernik, Federica Giardina, Petr Bednar, Andrea Fortova, Dora Mehn, Davide F. Robbiani, Natalie Polakova, Luca Varani, Ivana Bukova, Jolana Tureckova, Filippo Bianchini, Frauke Muecksch, Dagmar Zudova, Tereza Michalcikova, Antonio Piralla, Daniel Ruzek, Qiang Pan-Hammarström, Josè Camilla Sammartino, Salvatore Di Girolamo, Sabrina Gioria, Stefano Gaiarsa, Fausto Baldanti, Michel C. Nussenzweig, Blanka Mrazkova, Davide Magrì, Jan Prochazka, Raoul De Gasparo, Radislav Sedlacek, Julio C. C. Lorenzi, Christopher O. Barnes, Martin Palus, Luca Simonelli, Veronika Iatsiuk, Jan Rozman, Petr Nickl, Irene Cassaniti, Pamela J. Bjorkman, Paul D. Bieniasz, Petra Straková, Mattia Pedotti, Oto Pavlis, Elena Percivalle, Václav Hönig, Radim Nencka, and Theodora Hatziioannou
- Subjects
0301 basic medicine ,Antagonists & inhibitors ,medicine.drug_class ,viruses ,Protein design ,Mutant ,Monoclonal antibody ,Virus ,Epitope ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Antibodies, Bispecific ,medicine ,Animals ,Humans ,Immune Evasion ,Multidisciplinary ,biology ,SARS-CoV-2 ,Chemistry ,Body Weight ,Antibodies, Monoclonal ,COVID-19 ,virus diseases ,Dependovirus ,respiratory system ,Antibodies, Neutralizing ,Publisher Correction ,Virology ,COVID-19 Drug Treatment ,3. Good health ,respiratory tract diseases ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,Immunization ,Viral infection ,Immunoglobulin G ,Spike Glycoprotein, Coronavirus ,biology.protein ,Epitopes, B-Lymphocyte ,Female ,Angiotensin-Converting Enzyme 2 ,Antibody therapy ,Antibody ,030217 neurology & neurosurgery - Abstract
Neutralizing antibodies that target the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein are among the most promising approaches against COVID-191,2. A bispecific IgG1-like molecule (CoV-X2) has been developed on the basis of C121 and C135, two antibodies derived from donors who had recovered from COVID-193. Here we show that CoV-X2 simultaneously binds two independent sites on the RBD and, unlike its parental antibodies, prevents detectable spike binding to the cellular receptor of the virus, angiotensin-converting enzyme 2 (ACE2). Furthermore, CoV-X2 neutralizes wild-type SARS-CoV-2 and its variants of concern, as well as escape mutants generated by the parental monoclonal antibodies. We also found that in a mouse model of SARS-CoV-2 infection with lung inflammation, CoV-X2 protects mice from disease and suppresses viral escape. Thus, the simultaneous targeting of non-overlapping RBD epitopes by IgG-like bispecific antibodies is feasible and effective, and combines the advantages of antibody cocktails with those of single-molecule approaches. The bispecific IgG1-like CoV-X2 prevents SARS-CoV-2 spike binding to ACE2, neutralizes SARS-CoV-2 and its variants of concern, protects against disease in a mouse model, whereas the parental monoclonal antibodies generate viral escape.
- Published
- 2021
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