A Neonatal Swine Model of Allergy Induced by the Major Food Allergen Chicken Ovomucoid (Gal d 1)

Abstract

Background: Food allergy is a serious health problem for which a validated outbred large animal model would be useful in comparative investigations of immunopathogenesis and treatment and in testing hypotheses relevant to complex host-environmental interactions in predisposition to and expression of food allergy. Objective: To establish a neonatal swine model of IgE-mediated allergy to the egg protein ovomucoid (Ovm) that may mimic human allergy. Methods: In order to induce Ovm sensitivity, piglets at days 14, 21 and 35 of age were sensitized by intraperitoneal injection of 100 µg of crude Ovm and cholera toxin (50, 25 or 10 µg). Controls received 50 µg of cholera toxin in phosphate-buffered saline. The animals were challenged orally on day 46 with a mixture of egg white and yoghurt. Outcomes were reported as direct skin tests, clinical signs, IgG-related antibody and passive cutaneous anaphylaxis. Results: Sensitized pigs developed immediate wheal and flare reactions, and after oral challenge, sensitized but not control animals displayed signs of allergic hypersensitivity. Serum IgG-related, Ovm-specific antibodies were detected only in the sensitized pigs and IgE-mediated antibody response to Ovm was confirmed by positive passive cutaneous anaphylaxis reactions induced by sera of sensitized but not by heat-treated sera from Ovm-sensitized pigs or sera of unsensitized control pigs. Conclusion: The present results confirm induction of Ovm-specific allergy in pigs and provide opportunity to investigate allergic predisposition and immunopathogenesis of IgE-induced Ovm allergy using outbred neonatal swine. This may better simulate allergic disease in humans and allow investigation of candidate prophylactic and therapeutic approaches.

Anaphylactic shock due to hepatitis B immunoglobulin in a newborn

“…However, proven reports of patients and animal studies with anaphy-laxis are available in limited number in the literature [5]. Rare cases of newborns with anaphylaxis or anaphylactoid shock due to ceftriaxone, thiopentone, atracurium, cow's milk protein, old-dissolved immunoglobulin and BCG vaccination have also been reported [6][7][8][9][10].…”

Rearing environment affects development of the immune system in neonates

“…There is an increasing perception that the pig presents a number of advantages as a pre-clinical, translational model for humans [9][10][11][12]. Like humans, the pig is a large, monogastric omnivore with highly comparable intestinal anatomy, physiology and nutritional requirements [13,14].…”

Effect of Heat-Killed Escherichia coli, Lipopolysaccharide, and Muramyl Dipeptide Treatments on the Immune Response Phenotype and Allergy in Neonatal Pigs Sensitized to the Egg White Protein Ovomucoid

“…In addition, pigs are outbred, similar to humans, perhaps better mimicking the effect of environmental influences than do inbred mice. The clinical signs of allergy in pigs are similar to those in humans, and several studies have been reported (11,15,16,32,33,35,41).…”

“…On days 14, 21, and 35, intraperitoneal (i.p.) injections of 100 g of purified Ovm, prepared in lab (33), adjuvanted with 10 g of cholera toxin (List Biologicals, CA), were given to all pigs as previously described (33). Blood was taken from the retro-orbital sinus on day 45 to measure the effect of each treatment on bias of IR phenotype.…”