Bispecific antibody neutralizes circulating SARS-CoV-2 variants, prevents escape and protects mice from disease
De Gasparo, R.; Pedotti, M.; Simonelli, L.; Nickl, P.; Muecksch, F.; Cassaniti, I.; Percivalle, E.; Lorenzi, J. C. C.; Mazzola, F.; Magri, D.; Michalcikova, T.; Haviernik, J.; Honig, V.; Mrazkova, B.; Polakova, N.; Fortova, A.; Tureckova, J.; Iatsiuk, V.; Di Girolamo, S.; Palus, M.; Zudova, D.; Bednar, P.; Bukova, I.; Bianchini, F.; Mehn, D.; Nencka, R.; Strakova, P.; Pavlis, O.; Rozman, J.; Gioria, S.; Sammartino, J. C.; Giardina, F.; Gaiarsa, S.; Hammarström, Q. P.; Barnes, C. O.; Bjorkman, P. J.; Calzolai, L.; Piralla, A.; Baldanti, F.; Nussenzweig, M. C.; Bieniasz, P. D.; Hatziioannou, T.
Show 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.
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