Polymeric IgA with unique glycans protects from necrotoxigenic E. coli O55 infection in an animal model

Abstract

Antibodies exhibit protective activities through their antigen-specific Fab-dependent interactions and by the Fc-associated glycan moieties. To evaluate the protective functions of Ig-associated glycans, we compared in vitro and in vivo the human polyclonal secretory (S) IgA with polymeric (p) monoclonal myeloma IgA proteins of defined glycan structure for their protective activity against necrotoxigenic E. coli O55. Namely, we compared the adhesion and penetration of necrotoxigenic E. coli O55 to a pig intestinal IPEC-1 cells and determined the IPEC-1 response relative to the preincubation of bacteria with various pIgA1 or pIgA2. Preparation designated pIgA2(F2) exhibiting unique N-glycan composition and the highest protection in vitro was tested in vivo with respect to the protection against experimental intestine infection of antibody-free newborn piglets by E. coli O55. pIgA2(F2) reduced inflammatory activation of gut tissue, prevents development of alterations of intestinal architecture including villous blunting and epithelial hyperplasia equally to simultaneously tested milk/colostrum-derived SIgA. Further studies would lead to the identification of pIgA2 glycans involved in the protection from specific bacterial gut infection.