Fig. 3: ADE of SARS-CoV-2 infection requires bivalent interaction of mAb with SARS-CoV-2 S trimer.

a Superimposition of MW01/RBD and MW05/RBD with MW07/RBD. The SARS-CoV-2 RBD is colored in gray surface. Heavy chain and light chain of MW01, MW05, and MW07 are presented in the cartoon with the same colors in Fig. 2. b Compare the association signals of MW01, MW05, and MW07 to SARS-CoV-2 S trimer performed by BIAcore T200 system. Recombinant SARS-CoV-2 S trimer protein was captured on the CM5 chip via anti-his antibody at about 200 response units. 2-fold serially diluted MW01, MW05, and MW07 antibody starting from 125 nM were then flowed over the chip surface. c Schematic illustration of the wild-type mAb (hIgG1), knob-in-hole format bivalent mAb (hIgG1/KIH) and monovalent mAb (hIgG1/KIH-Mo). hIgG1/KIH-Mo was generated by substitution of hole chain VH domain with an irrelevant antibody. The irrelevant VH domain is colored with gray. d, e Measurement of the dissociation signals of MW01/KIH and MW01/KIH-Mo. NTA biosensor chip was used to capture SARS-CoV-2 S trimer on BIAcore S200 system. 2-fold serially diluted MW01/KIH and MW01/KIH-Mo starting from 100 nM were then flowed over the chip surface. f Compare the SARS-CoV-2 neutralization potencies of wild-type, KIH format bivalent, and monovalent antibodies using SARS-CoV-2 pseudovirus system. g Compare the ADE of SARS-CoV-2 infection on Raji cells mediated by wild-type, KIH format bivalent, and monovalent antibodies. h Compare the ADE of SARS-CoV-2 infection on Raji cells mediated by MW05, CR3022, and MW05/CR3022 mixture.