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

0544120 - ÚMG 2022 RIV GB eng J - Journal Article
De Gasparo, R. - Pedotti, M. - Simonelli, L. - Nickl, Petr - Muecksch, F. - Cassaniti, I. - Percivalle, E. - Lorenzi, J.C.C. - Mazzola, F. - Magri, D. - Michalčíková, Tereza - Haviernik, J. - Hönig, Václav - Mrázková, Blanka - Poláková, Natálie - Fořtová, A. - Turečková, Jolana - Iatsiuk, Veronika - Di Girolamo, S. - Palus, Martin - Zudová, Dagmar - Bednář, P. - Buková, Ivana - Bianchini, F. - Mehn, D. - Nencka, Radim - Straková, P. - Pavlis, O. - Rozman, Jan - Gioria, S. - Sammartino, J.C. - Giardina, F. - Gaiarsa, S. - Pan-Hammarstrom, Q. - Barnes, C.O. - Bjorkman, P.J. - Calzolai, L. - Piralla, A. - Baldanti, F. - Nussenzweig, M.C. - Bieniasz, P.D. - Hatziioannou, T. - Procházka, Jan - Sedláček, Radislav - Robbiani, D.F. - Růžek, Daniel - Varani, L.
Bispecific IgG neutralizes SARS-CoV-2 variants and prevents escape in mice.
Nature. Roč. 593, č. 7859 (2021), s. 424-428. ISSN 0028-0836. E-ISSN 1476-4687
R&D Projects: GA MŠMT(CZ) LM2018126; GA MŠMT ED2.1.00/19.0395; GA MŠMT(CZ) ED1.1.00/02.0109; GA ČR(CZ) GA20-14325S
Institutional support: RVO:68378050 ; RVO:61388963 ; RVO:60077344
Keywords : virus * infection * mutations * domain
OECD category: Virology; Virology (BC-A)
Impact factor: 69.504, year: 2021
Method of publishing: Limited access
https://www.nature.com/articles/s41586-021-03461-y

Neutralizing antibodies that target the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein are among the most promising approaches against COVID-19(1,2). 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-19(3). 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.
Permanent Link: http://hdl.handle.net/11104/0321170