Chemically modified peanut extract shows increased safety while maintaining immunogenicity

Abstract

Background: Peanuts are most responsible for food-induced anaphylaxis in adults in developed countries. An effective and safe immunotherapy is urgently needed. The aim of this study was to investigate the immunogenicity, allergenicity, and immunotherapeutic efficacy of a well-characterized chemically modified peanut extract (MPE) adsorbed to Al(OH) 3 . Methods: Peanut extract (PE) was modified by reduction and alkylation. Using sera of peanut-allergic patients, competitive IgE-binding assays and mediator release assays were performed. The immunogenicity of MPE was evaluated by measuring activation of human PE-specific T-cell lines and the induction of PE-specific IgG in mice. The safety and efficacy of MPE adsorbed to Al(OH) 3 was tested in two mouse models by measuring allergic manifestations upon peanut challenge in peanut-allergic mice. Results: Compared to PE, the IgE-binding and capacity to induce allergic symptoms of MPE were lower in all patients. PE and MPE displayed similar immunogenicity in vivo and in vitro. In mice sensitized to PE, the threshold for anaphylaxis (drop in BT) upon subcutaneous challenge with PE was 0.01 mg, while at 0.3 mg MPE no allergic reaction occurred. Anaphylaxis was not observed when PE and MPE were fully adsorbed to Al(OH) 3 . Both PE and MPE + Al(OH) 3 showed to be efficacious in a model for immunotherapy. Conclusion:In our studies, an Al(OH) 3 adsorbed MPE showed reduced allergenicity compared to unmodified PE, while the efficacy of immunotherapy is maintained.

Lactobacillus Casei Zhang Alleviates Shrimp Tropomyosin‐Induced Food Allergy by Switching Antibody Isotypes through the NF‐κB‐Dependent Immune Tolerance

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Mouse models of atopic dermatitis: a critical reappraisal

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Future research trends in understanding the mechanisms underlying allergic diseases for improved patient care

“…The major issues in treating food allergy by immunotherapy are safety, the low rate of tolerance induction, a high rate of side effects and dropouts, a lack of understanding of the optimal dose and time of treatment, and the existence of only few, suboptimal biomarkers that predict treatment response and how to perform multifood OIT . These limitations are addressed in numerous treatment approaches: (a) peptide immunotherapy targeting the T‐cell compartment and lacking IgE cross‐linking; (b) hypoallergenic variants of allergens or extracts by chemical or thermal modification or mutations which combine reduced desensitization with a minimally altered T‐cell epitope diversity; (c) the usage of immunomodulatory substances and/or particles; (d) the addition of prebiotics and/or probiotics; (e) the application of biologics either alone or as adjuvants of OIT; (g) very low dose OIT; and (h) sublingual OIT.…”