Figure 5.

Neutralization of 12-16 and 12-19 is Fc independent

(A) Binding kinetics and affinities of 12-16, 12-19, and 4-18 in the formats of IgG, F(ab′)2, and Fab to SARS-CoV-2 D614G S2P spike trimer.

(B) Neutralization curves and IC₅₀ values of 12-16, 12-19, and 4-18 in the formats of IgG, F(ab′)2, and Fab against D614G. The NTD-directed mAb 4-18 in F(ab′)2 format showed weakened neutralization activity against D614G due to the lack of Fc, whereas F(ab′)2 of 12-16 and 12-19 retained unimpaired potency, suggesting that the neutralizing activities of 12-16 and 12-19 are Fc independent. Data are shown as mean ± SEM.

(C) 12-16 and 12-19 maintain the spike at a conformational state with all 3 RBD in the down position, thereby blocking ACE2 binding. IgG and F(ab′)2 formats would benefit from avidity effects such as spike cross-linking, demonstrated by superimposing 12-16 and 12-19 Fab structures on IgG structure (PDB: 1igt).

Data in (A) and (B) are representative from one of the three independent experiments.