Fig 1: IgG1-IgA2m1 Fc fusions and aglycosylated IgA2m2 show improved serum exposures compared to wild-type IgA in vivo and demonstrate the ability to transcytose in vitro.(A) Schematic of IgA2m2 tetramer with light chain (LC, yellow), heavy chain (HC, blue) and joining chain (JC, green) with 41 N-linked glycosylation sites (gray) (left) or aglycosylated (right). (B) Schematic of IgG1, IgA2m1 dimer, or IgG1-IgA2m1 Fc dimer formats with LC (yellow), IgG1 HC (orange), IgA2m1 HC (blue), JC (green), and N-linked glycosylation (gray). (C) Analytical SEC of iodinated IgG1-IgA2m1 Fc dimers or tetramer after 0 h (black), 24 h (orange) or 96 h (blue) incubation in mouse plasma. The initial IgG1-L-P221R IgA2m1 Fc tetramer and dimer show degradation similar to the peak of anti-HER2 IgG1 (Trastuzumab) control, whereas the reengineered IgG1ΔK-P221 IgA2m1 Fc or IgG1ΔK-C242 IgA2m1 Fc dimers are stable. (D) Serum-time concentration profiles of IgA or IgG in mice. The overall serum exposures of Balb/c mice administered with a single 30 mg/kg IV dose of IgA molecules. The in-house concentration data of a typical human IgG1 (anti-gD) previously dosed as a single intravenous (IV) injection at 30 mg/kg are shown as a dashed line. All mice were bled retro-orbitally or via cardiac puncture under isoflurane to evaluate serum concentration profile. (E) In vitro transcytosis of hIgA in MDCK cells transfected with human pIgR.