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Journal article
Designer covalent heterobivalent inhibitors prevent IgE-dependent responses to peanut allergen
Proceedings of the National Academy of Sciences - PNAS, v 116(18), pp 8966-8974
30 Apr 2019
PMID: 30962381
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Allergies are a result of allergen proteins cross-linking allergen-specific IgE (sIgE) on the surface of mast cells and basophils. The diversity and complexity of allergen epitopes, and high-affinity of the sIgE-allergen interaction have impaired the development of allergen-specific inhibitors of allergic responses. This study presents a design of food allergen-specific sIgE inhibitors named covalent heterobivalent inhibitors (cHBIs) that selectively form covalent bonds to only sIgEs, thereby permanently inhibiting them. Using screening reagents termed nanoallergens, we identified two immunodominant epitopes in peanuts that were common in a population of 16 allergic patients. Two cHBIs designed to inhibit only these two epitopes completely abrogated the allergic response in 14 of the 16 patients in an in vitro assay and inhibited basophil activation in an allergic patient ex vivo analysis. The efficacy of the cHBI design has valuable clinical implications for many allergen-specific responses and more broadly for any antibody-based disease.
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Details
- Title
- Designer covalent heterobivalent inhibitors prevent IgE-dependent responses to peanut allergen
- Creators
- Peter E Deak - Drexel University, Chemical and Biological EngineeringBaksun Kim - Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, IN 46556Amina Abdul Qayum - Indiana UniversityJaeho Shin - University of Notre DameGirish Vitalpur - Riley Hospital for ChildrenKirsten M Kloepfer - Riley Hospital for ChildrenMatthew J Turner - Indiana UniversityNeal Smith - Harvard UniversityWayne G Shreffler - Harvard UniversityTanyel Kiziltepe - University of Notre DameMark H Kaplan - Indiana UniversityBasar Bilgicer (Corresponding Author) - University of Notre Dame
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, v 116(18), pp 8966-8974
- Publisher
- PNAS
- Grant note
- R01 AI108884 / NIAID NIH HHS U54 DK106846 / NIDDK NIH HHS P30 CA082709 / NCI NIH HHS T32 DK007519 / NIDDK NIH HHS R01 AI129241 / NIAID NIH HHS U19 AI095261 / NIAID NIH HHS L40 AI096442 / NIAID NIH HHS IK2 CX001019 / CSRD VA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Chemical and Biological Engineering
- Web of Science ID
- WOS:000466446500050
- Scopus ID
- 2-s2.0-85065510463
- Other Identifier
- 991019376908804721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Immunology