Masked Delivery of Allergen in Nanoparticles Safely Attenuates Anaphylactic Response in Murine Models of Peanut Allergy.

Th2 antigen-specific therapy food allergy nanoparticle tolerance

Journal

Frontiers in allergy
ISSN: 2673-6101
Titre abrégé: Front Allergy
Pays: Switzerland
ID NLM: 9918227355906676

Informations de publication

Date de publication:
2022
Historique:
received: 06 12 2021
accepted: 12 01 2022
entrez: 7 4 2022
pubmed: 8 4 2022
medline: 8 4 2022
Statut: epublish

Résumé

Food allergy is a growing health concern worldwide. Current allergen-specific immunotherapy (AIT) approaches require frequent dosing over extended periods of time and may induce anaphylaxis due to allergen-effector cell interactions. A critical need remains to develop novel approaches that refine AIT for the treatment of food allergies. Previous studies show that poly(lactide-co-glycolide) (PLG) nanoscale particles (NP) effectively suppress Th1- and Th17-driven immune pathologies. However, their ability to suppress the distinct Th2-polarized immune responses driving food allergy are unknown. Herein, we describe the safety and efficacy of NPs containing encapsulated peanut allergen in desensitizing murine models of peanut allergy. Peanut extract encapsulation allowed for the safe intravenous delivery of allergen relative to non-encapsulated approaches. Application of 2-3 doses, without the need for dose escalation, was sufficient to achieve prophylactic and therapeutic efficacy, which correlated with suppression of Th2-mediated disease and reduced mast cell degranulation. Efficacy was associated with strong reductions in a broad panel of Th1, Th2, and Th17 cytokines. These results demonstrate the ability of PLG NPs to suppress allergen-specific immune responses to induce a more tolerogenic phenotype, conferring protection from intragastric allergen challenge. These promising studies represent a step forward in the development of improved immunotherapies for food allergy.

Identifiants

pubmed: 35386645
doi: 10.3389/falgy.2022.829605
pmc: PMC8974743
doi:

Types de publication

Journal Article

Langues

eng

Pagination

829605

Subventions

Organisme : NIAID NIH HHS
ID : R01 AI155678
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007863
Pays : United States

Informations de copyright

Copyright © 2022 Hughes, Saunders, Landers, Janczak, Turkistani, Rad, Miller, Podojil, Shea and O'Konek.

Déclaration de conflit d'intérêts

LS, JP, and SM have financial interests in COUR Pharmaceuticals Development Co. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Auteurs

Kevin R Hughes (KR)

Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, United States.

Michael N Saunders (MN)

Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, United States.
Medical Scientist Training Program, University of Michigan, Ann Arbor, MI, United States.

Jeffrey J Landers (JJ)

Mary H. Weiser Food Allergy Center, Michigan Medicine, Ann Arbor, MI, United States.

Katarzyna W Janczak (KW)

Mary H. Weiser Food Allergy Center, Michigan Medicine, Ann Arbor, MI, United States.

Hamza Turkistani (H)

Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, United States.

Laila M Rad (LM)

Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, United States.

Stephen D Miller (SD)

Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.
Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.

Joseph R Podojil (JR)

Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.
COUR Pharmaceuticals Development Co, Inc., Northbrook, IL, United States.

Lonnie D Shea (LD)

Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, United States.
Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, United States.
Department of Surgery, University of Michigan, Ann Arbor, MI, United States.

Jessica J O'Konek (JJ)

Mary H. Weiser Food Allergy Center, Michigan Medicine, Ann Arbor, MI, United States.

Classifications MeSH