SENSITIZATION AND ALLERGIC RESPONSE AND INTERVENTION THERAPY IN ANIMAL MODELS

Authors: HELM, RICKI - UAMS/ACNC; BURKS, WESLEY - DUKE UNIV MED CTR/PEDS

Submitted to: Association of Analytical Communities International Midwest Section
Publication Type: Review Article
Publication Acceptance Date: 10/22/2004
Publication Date: 10/30/2004
Citation: Helm, R.M., Burks, W.A. 2004. Sensitization and allergic response and intervention therapy in animal models. Association of Analytical Communities International. 87(6):1269-1277.

Interpretive Summary: Peanut food allergy appears to be increasing worldwide. At present the only treatment option is strict avoidance of peanut and products containing peanuts as a component of processed foods. In order to reduce the allergic response to accidental ingestion of processed foods containing peanuts that are not labeled adequately to warn individuals sensitive to peanuts from eating these products, several lines of research have been investigated to reduce allergic symptoms upon hidden peanut exposure. This invited research note/review article presents three mouse models and a swine newborn model that addresses potential treatment regimens that could be used to reduce symptoms upon exposure to peanuts in peanut-allergic individuals. Modifications to peanut allergens or that do not bind the immunoglobulin (IgE) responsible for determining food allergy symptoms are being investigated in the author’s research laboratories that could potentially be extrapolated to use in treatment options. Another alternative under investigation is the use of clinically irrelevant foods such as soybeans that do not cause peanut allergy symptoms. Evidence to date clearly suggests that continued research efforts in these animal models will need to be investigated before applications can be made in the treatment of peanut allergic individuals.

Technical Abstract: A review is presented of 3 murine models and a swine neonatal model used to investigate immunotherapeutic options. In Model 1, mutation of linear IgE-binding epitopes of Ara h 1 for the preparation of a hypoallergenic Ara h 1 is discussed with respect to expression in transgenic tobacco plants and correct folding following expression in the pET16b construct. In Model 2, the mutations of Ara h 1 were assessed for use as an immunotherapeutic agent. Although some protective benefit was observed with the modified Ara h 1 protein, animals desensitized with heat-killed E. coli preparations showed increased protection to challenge. In Model 3, soybean homologs to peanut proteins were investigated to determine if soybean immunotherapy can potentially provide benefit to peanut-allergic subjects. Although some protection was provided, additional experimentation with respect to optimal doses for sensitization and challenge will need to be investigated. In Model 4, the neonatal swine model was used to profile different foods (low to moderate to high sensitizing) similar to food allergies in humans. Evidence suggests such feasiblity; however, threshold levels for sensitization and allergic responses will need additional study. In summary, murine and swine animal models are being used to address immunotherapeutic avenues and investigation into the mechanisms of food-allergic sensitization.