Extended Data Fig. 4: Sotrovimab promotes Fc-mediated effector functions and protects against viral challenge with the SARS-CoV-2 BQ1.1 and XBB.1.5 variants.

a, Binding of the S2V29 monoclonal Ab to SARS-CoV-2 S variants expressed at the surface of ExpiCHO-S cells as measured by flow cytometry. S2V29 retains potent and equal binding against Wu-D614, BQ.1.1, XBB.1, XBB.1.5, BA.2, BN.1 and BA.2-E340A VSV pseudoviruses and was therefore used for quantifying cell-surface S expression. b, Correlation of sotrovimab Fab binding affinity with ADCP. The ADCP AUC values from Fig. 3d are plotted on the y-axis and the binding affinity to each RBD variant obtained in Fig. 3b is plotted on the x-axis. Dotted lines indicate the limit of detection for binding affinity and the mean of S309-GRLR AUCs from the different variants. c, ExpiCHO cells transiently transfected with S variants were incubated with the indicated concentrations of sotrovimab or S309-GRLR (G236R/L328R loss-of-function mutations introduced in the Fc domain of the human IgG1 heavy chain) and mixed with NK cells isolated from healthy donors in a range from 6:1 to 9:1 (NK:target cells). Target cell lysis was determined by a lactate dehydrogenase release assay. Data are presented as mean values +/– standard deviations (SD) from duplicates obtained using NK cells from two representative donors, both being homozygous for genotype V/V158 FcγRIIIa. d, ExpiCHO cells transiently transfected with S variants were fluorescently labelled with PKH67, incubated with the indicated concentrations of sotrovimab or S309-GRLR mAb and mixed with PBMCs labelled with CellTrace Violet from two healthy donors heterozygous for genotype R/H131 FcγRIIa at a ratio of 20:1 (PBMC:target cells). Association of CD14⁺ monocytes with S-expressing target cells (ADCP) was determined by flow cytometry. e, Eight-week-old female K18-hACE2 mice received 3, 10 or 30 mg/kg of S309 (parent of sotrovimab) or S309-GRLR or 30 mg/kg of an isotype-matched control monoclonal Ab (anti-West Nile virus hE16⁵¹) by intraperitoneal injection one day before intranasal inoculation with 10⁴ FFU of SARS-CoV-2 BQ.1.1. n = 9–20 animals per group. Tissues were collected at six days after infection. Lung live virus titer (left panel) and nasal turbinate (center panel) or nasal wash (right panel) viral RNA determined by RT-qPCR on day 6 are plotted (short, solid lines indicate the median; dotted lines indicate the LLOQ; n = 9–20 mice per group; Kruskal-Wallis ANOVA with Dunn’s post-test; ns, not significant; *P < 0.05, **P < 0.01, ***P < 0.001, **** P < 0.0001). f, Serum concentration of S309 hamster IgG2a measured by ELISA at day 4 post-infection. n = 6 hamsters per group.The horizontal bar represents the median.