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

R. De Gasparo, M. Pedotti, L. Simonelli, P. Nickl, F. Muecksch, I. Cassaniti, E. Percivalle, JCC. Lorenzi, F. Mazzola, D. Magrì, T. Michalcikova, J. Haviernik, V. Honig, B. Mrazkova, N. Polakova, A. Fortova, J. Tureckova, V. Iatsiuk, S. Di...

. 2021 ; 593 (7859) : 424-428. [pub] 20210325

Language English Country Great Britain

Document type Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc21018727

Grant support
U01 AI151698 NIAID NIH HHS - United States
P01-AI138398-S1 NIH HHS - United States
2U19AI111825 NIH HHS - United States
Howard Hughes Medical Institute - United States
P50 AI150464 NIAID NIH HHS - United States
R37 AI064003 NIAID NIH HHS - United States
R01 AI078788 NIAID NIH HHS - United States

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.

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$a Bispecific IgG neutralizes SARS-CoV-2 variants and prevents escape in mice / $c R. De Gasparo, M. Pedotti, L. Simonelli, P. Nickl, F. Muecksch, I. Cassaniti, E. Percivalle, JCC. Lorenzi, F. Mazzola, D. Magrì, T. Michalcikova, J. Haviernik, V. Honig, B. Mrazkova, N. Polakova, A. Fortova, J. Tureckova, V. Iatsiuk, S. Di Girolamo, M. Palus, D. Zudova, P. Bednar, I. Bukova, F. Bianchini, D. Mehn, R. Nencka, P. Strakova, O. Pavlis, J. Rozman, S. Gioria, JC. Sammartino, F. Giardina, S. Gaiarsa, Q. Pan-Hammarström, CO. Barnes, PJ. Bjorkman, L. Calzolai, A. Piralla, F. Baldanti, MC. Nussenzweig, PD. Bieniasz, T. Hatziioannou, J. Prochazka, R. Sedlacek, DF. Robbiani, D. Ruzek, L. Varani
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