Designer covalent heterobivalent inhibitors prevent IgE-dependent responses to peanut allergen

Peter E. Deak, Baksun Kim, Amina Abdul Qayum, Jaeho Shin, Girish Vitalpur, Kirsten M. Kloepfer, Matthew J. Turner, Neal Smith, Wayne G. Shreffler, Tanyel Kiziltepe, Mark Kaplan, Basar Bilgicer

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)8966-8974
Number of pages9
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number18
DOIs
StatePublished - Apr 30 2019

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Allergens
Immunoglobulin E
Basophils
Epitopes
Immunodominant Epitopes
Mast Cells
Arachis
Hypersensitivity
Food
Antibodies
Population
Proteins

Keywords

  • Allergy
  • Epitope
  • IgE
  • Peanut
  • Selective inhibition

ASJC Scopus subject areas

  • General

Cite this

Designer covalent heterobivalent inhibitors prevent IgE-dependent responses to peanut allergen. / Deak, Peter E.; Kim, Baksun; Qayum, Amina Abdul; Shin, Jaeho; Vitalpur, Girish; Kloepfer, Kirsten M.; Turner, Matthew J.; Smith, Neal; Shreffler, Wayne G.; Kiziltepe, Tanyel; Kaplan, Mark; Bilgicer, Basar.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 116, No. 18, 30.04.2019, p. 8966-8974.

Research output: Contribution to journalArticle

Deak, PE, Kim, B, Qayum, AA, Shin, J, Vitalpur, G, Kloepfer, KM, Turner, MJ, Smith, N, Shreffler, WG, Kiziltepe, T, Kaplan, M & Bilgicer, B 2019, 'Designer covalent heterobivalent inhibitors prevent IgE-dependent responses to peanut allergen', Proceedings of the National Academy of Sciences of the United States of America, vol. 116, no. 18, pp. 8966-8974. https://doi.org/10.1073/pnas.1820417116
Deak, Peter E. ; Kim, Baksun ; Qayum, Amina Abdul ; Shin, Jaeho ; Vitalpur, Girish ; Kloepfer, Kirsten M. ; Turner, Matthew J. ; Smith, Neal ; Shreffler, Wayne G. ; Kiziltepe, Tanyel ; Kaplan, Mark ; Bilgicer, Basar. / Designer covalent heterobivalent inhibitors prevent IgE-dependent responses to peanut allergen. In: Proceedings of the National Academy of Sciences of the United States of America. 2019 ; Vol. 116, No. 18. pp. 8966-8974.
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