An IgA mimicry of IgG that binds Polymeric Immunoglobulin Receptor for mucosa transcytosis.

Most pathogens establish infection through mucosa, where secretary IgA (sIgA) plays an "immune exclusion" role in humoral defense. Extravasation of intravenously administrated therapeutic IgG mainly relies on convection and/or FcRn-mediated transcytosis from circulation into interstitial space. Active transport of interstitial IgG further across epithelium into mucosa, like sIgA, is a much desired feature for the next generation of therapeutic antibodies, especially for anti-infection purposes. For the first time, we report the engineering of an IgA mimicry of IgG, with its Fc portion in fusion with the 18-aa tail piece (tp) of sIgA and the J chain, possessing sIgA's full binding activity towards Polymeric Immunoglobulin Receptor (pIgR) that mediates mucosa transcytosis. In a Diphtheria toxin receptor (DTR) knockin mouse model, i.v. injected anti-DT IgG(tp)J protected DTR+ cells from deletion upon DT injection. The compact design of IgG(tp)J opens new revenues for more effective therapeutic IgG mimicking some of the important biological functions of IgA.