Induction of Allergic Responses to Peanut Allergen in Sheep

Abstract

Peanut allergy is the leading cause of deaths due to food-induced anaphylaxis but despite continued research, there are currently no specific treatments available. Challenge testing is limited in patients due to the high risk of adverse reactions, emphasising the need for an appropriate animal model. In the present study we examine the induction of allergic responses in a sheep model for peanut allergy. Sheep were sensitised with peanut (PN) extract and in separate injections with ovalbumin (OVA) or house dust mite (HDM) extract. Serum PN-specific IgE responses were detected in 40–50% of immunised sheep, while only 10% (1 of 10 sheep) showed detectable OVA-specific IgE. All PN-allergic sheep tested showed an Ara h 1-specific IgE response, while four out of five allergic sheep showed an Ara h 2-specific IgE response. Animals with high serum IgE levels to HDM were also PN IgE-positive. Of the PN-sensitised animals with high PN-specific IgE, 80% also showed an immediate hypersensitivity reaction following an intradermal PN injection. This new large animal model of peanut allergy may provide a useful tool for future investigations of allergen-associated immune mechanisms and specific immunotherapy.

Placental restriction of fetal growth reduces cutaneous responses to antigen after sensitization in sheep

“…1). Sheep were then sensitized to house dust mite allergen (HDM; CSL, Parkville, Australia) and ovalbumin (OVA; A2512, Sigma, MO), each administered mixed with aluminium hydroxide as adjuvant (1:1) by subcutaneous injections (2,39) at 20, 22, 24, and 26 wk of age. Immediate and delayed cutaneous responses (cutaneous hypersensitivity) to intradermal injections of 50 l saline (negative control), histamine (10 g/ml, H7375, Sigma), HDM (100 g/ml), and OVA (10 g/ml) were assessed at 28 wk of age (3).…”

“…IgM and IgA were assayed by ELISA as for total antigen-specific Ig (3,39), but with rabbit anti-ovine IgA (Bio-Rad AbD Serotec, Kidlington, UK), or rabbit anti-ovine IgM (diluted 1/5,000, Bio-Rad AbD Serotec, Kidlington, UK) as primary antibody, and HRP-conjugated swine anti-rabbit Ig (diluted 1/1,000, Dako, Glostrup, Denmark) as secondary antibody. Antibody responses to sensitization were classified as positive when they increased by greater than two fold relative to basal concentrations.…”

Animal Models of Allergic Diseases

“…The most commonly used strain is the brown Norway able to produce allergen specific IgE after oral sensitization and able to predict the allergenicity of novel proteins [110,111]. Other strains like Wistar, Hooded Lister, and Piebald Virol Glaxo have been studied, but not commonly used due to the inability to detect quantifiable levels of antigen specific IgE [112].…”

Use of Animal Models to Investigate Major Allergens Associated with Food Allergy

“…Sheep have previously been used for allergy studies involving house dust mite (HDM) allergen with a focus on human allergic asthma [37, 51], and more recently as a model for peanut food allergy [30]. Some key advantages of using large animal models include their outbred nature, allowing studies that are more comparable to humans, the ability to conduct serial experiments within the same cohort of animals, and their relative longevity, allowing more relevant investigations into chronic disease as well as the long-term evaluation of specific therapies [37, 50].…”

“…More recent studies report the use of sheep as a model for PN allergy involving animals sensitised via SC injections of crude PN extract (100  μ g) with Alum as adjuvant [30]. Sensitisation was achieved following 3 SC injections at 2-week intervals, followed by a “boost” injection after a 1-month rest period.…”