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Allergy. 2018 Dec 2. doi: 10.1111/all.13687. [Epub ahead of print]

Chemically modified peanut extract shows increased safety while maintaining immunogenicity.

Author information

1
HAL Allergy B.V., Leiden, The Netherlands.
2
Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
3
Department of Otorhinolaryngology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
4
Institute for Risk Assessment Sciences, Immunotoxicology, Utrecht University, Utrecht, The Netherlands.
5
Division of Allergy and Clinical Immunology, Department of Medicine, Denver School of Medicine, University of Colorado, Aurora, Colorado.
6
Department Dermatology/Allergology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
7
University of Nebraska, Lincoln, Nebraska.

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. The preclinical data presented in this study supports further development of modified peanut allergens for IT.

KEYWORDS:

immunogenicity; modification; mouse model; peanut allergy; subcutaneous immunotherapy

PMID:
30506686
DOI:
10.1111/all.13687

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