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

Mucosal immunoglobulin A (IgA) promotes the survival of commensal bacteria while it inhibits the invasion by pathogens. Bacterial coating may be mediated by antigen-specific IgA recognition, polyreactivity, and/or by the IgA-associated glycans. We compared human polyclonal secretory SIgA both in vitro and in vivo with polymeric (p) monoclonal myeloma IgA proteins of defined glycan structures to assess their protective activity against necrotoxigenic Escherichia coli O55. Specifically, we evaluated the adhesion and penetration of E. coli O55 into porcine intestinal IPEC-1 cells following preincubation of the bacteria with various pIgA1 or pIgA2 preparations. The preparation designated pIgA2(F2), which exhibited a unique N-glycan composition and demonstrated the highest level of protection in vitro, was further tested in vivo in an experimental intestinal infection model using antibody-free newborn piglets. In brief, pIgA2(F2) effectively reduced inflammatory activation of gut tissue and prevented pathological alterations in intestinal architecture, performing equally well as concurrently tested milk/colostrum-derived SIgA. Future studies would lead to the identification of the specific pIgA2-associated glycans responsible for mediating protection against targeted bacterial gut infections.