Summary
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.
Competing Interest Statement
In connection with this work the Institute for Research in Biomedicine has filed a provisional patent application on which L.V. is inventor (PCT/EP2020/085342). The Rockefeller University has filed a provisional patent application on which D.F.R. and M.C.N. are inventors.
Footnotes
- Bispecific neutralizes SARS-CoV-2 and its recent variants of concerns (colloquially known as UK, Brazil and S.Africa) in neutralization assays with infectious virus. - Bispecific therapeutically protects animals when administered after virus infection.
