Natural Pig Plasma Immunoglobulins Have Anti-Bacterial Effects: Potential for Use as Feed Supplement for Treatment of Intestinal Infections in Pigs

Hedegaard, Chris J.; Strube, Mikael L.; Hansen, Marie B.; Lindved, Bodil K.; Lihme, Allan; Boye, Mette; Heegaard, Peter M. H.

The purified pig IgG product (ppIgG) can be assumed to represent a population of natural antibodies having broad specificities against a vast number of pathogens and epitopes, comparable with Intravenous immunoglobulin (IVIg) preparations widely used for human applications [1] . We hypothesise that such purified immunoglobulin preparations may contain reactivity against a wide selection of pathogens infecting through the enteric route as the ppIgG originates from slaughter swine presumably harbouring a multitude of different anti-pathogenic immunoglobulins reflecting the exposure to many different infectious agents throughout the pig's life, including diarrhoeagenic E. coli. Hence, providing these immunoglobulins orally is presumed to inhibit adhesion of bacterial pathogens to the intestinal (epithelial) cell wall by immunoglobulins binding to these bacteria. The ppIgG investigated here contained approximately 85% pure IgG. Our in vitro results suggest that substantial amounts of ppIgG need to be supplemented in the diet as at least 6 milligrams of ppIgG were needed to inhibit bacterial adhesion to intestinal epithelial cells. This probably reflects the fact that only a minor part of the natural plasma immunoglobulin pool contains binding activities directed against the specific bacterial species (E. coli and S. enterica) investigated here. It was demonstrated that ppIgG does have a preference for binding relevant bacteria such as E. coli and Salmonella enterica having negligible binding to Y. ruckeri, a fish pathogen with no relevance for pigs. The ppIgG investigated here bound three different E. coli isolates and one S. enterica isolate equally well. Also, the anti-bacterial IgG of ppIgG was found to bind strongly to bacterial epitopes as the binding strength (avidity) of ppIgG towards E. coli was equal to or greater than seen in other studies using urea to interfere with the antibody-antigen binding [24] [25] [26] [27] [28] . Thus natural immunoglobulins purified directly from pig plasma (ppIgG) bind strongly to potentially diarrhoeagenic bacteria and inhibit bacterial adhesion to intestinal cells suggesting the use of ppIgG as an antibiotics alternative for prevention and treatment of enteric infections. The present study establishes the potential of ppIgG purified directly from slaughterhouse blood waste as an antibiotics alternative when used as a feed additive. This supplements earlier studies on the effects of orally provided spray-dried plasma on growth and intestinal infections in both swine and chicken and further underlines the importance of immunoglobulins for the effect of SDPP [15, [29] [30] [31] [32] . Furthermore the usage of isolated immunoglobulins from plasma in preventing/treating enteric infections is supported by Pierce et al who found that the plasma proteins with high molecular weight (primarily IgG) reduced ETEC infections in weaner piglets [16] .