Bispecific IgG neutralizes SARS-CoV-2 variants and prevents escape in mice

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 PalusDagmar 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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
JournalNature
DOIs
Publication statusAccepted/In press - 2021

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Bispecific IgG neutralizes SARS-CoV-2 variants and prevents escape in mice'. Together they form a unique fingerprint.

Cite this