Fig. 5: In vivo delivery and half-life engineering (YTE) contribute to improved durability of functional DMAbs compared to bioprocessed rIgG in hFcRn mice.

6–8-week-old female hFcRn mice (n = 4 (WT) or 5 (WT-YTE) independent biological replicates) were administered plasmids encoding the indicated DMAb cocktails (100 µg/animal) or rIgG cocktails (100 µg protein/animal; IP). a Individual serum levels (and group GM ± GSD) of the indicated DMAbs or rIgG mAbs are shown (n = 12). Group titers at each time point were compared using a two-tailed Mann–Whitney U test. P values indicated. Fold (x) difference in average titers between the indicated groups at D60 post-administration is depicted. b Neutralizing activity of all individual hFcRn serum samples (n = 4–5/group) against wildtype (USA-WA1/2020) or B.1.351 and B.1.617.2 variant pseudoviruses; neutralization curves against WA1−2020 (best-fit lines and individual data points derived from technical replicates) are shown, along with matched ID50s against other indicated variants. c Relative reactivity of pooled sera from hFcRn mice against recombinant B.1.1.529/BA.1 spike trimer. Average absorbance curves (OD450) displayed (derived from technical replicates). d–f Sera harvested from BALB/c mice expressing the DMAb WT(m3) cocktail was pooled for evaluation: d Relative reactivity against recombinant spike trimers from B.1.1.529/BA.1 or the parental D614G strains. Average absorbance curves (OD450) of each pool displayed (derived from technical replicates). Naïve serum was used as a control (gray). e-f Neutralizing activity of pooled sera (best-fit lines and individual data points derived from technical replicates) against e B.1.1.529/BA.1 or f B.1.1.529/BA.2 pseudotyped viruses. Calculated IC50 values displayed. Binding and neutralization data has been repeated in >2 independent assays. Source data are provided as a Source Data file.