Use of a Liver-targeting Nanoparticle Platform to Intervene in Peanut-induced anaphylaxis through delivery of an Ara h2 T-cell Epitope

Qi Liu; Xiang Wang; Yu-Pei Liao; Chong Hyun Chang; Jiulong Li; Tian Xia; Andre E Nel

doi:10.1016/j.nantod.2021.101370

Use of a Liver-targeting Nanoparticle Platform to Intervene in Peanut-induced anaphylaxis through delivery of an Ara h2 T-cell Epitope

Nano Today. 2022 Feb:42:101370. doi: 10.1016/j.nantod.2021.101370. Epub 2021 Dec 31.

Authors

Qi Liu^{1

2}, Xiang Wang^{1

2}, Yu-Pei Liao^{1

2}, Chong Hyun Chang^{1

2}, Jiulong Li^{1

2}, Tian Xia^{1

2

3}, Andre E Nel^{1

2

3}

Affiliations

¹ Center of Environmental Implications of Nanotechnology (UC CEIN), University of California, Los Angeles, CA 90095, USA.
² California NanoSystems Institute, University of California, Los Angeles, CA 90095, USA.
³ Division of NanoMedicine, Department of Medicine, University of California, Los Angeles, CA 90095, USA.

Abstract

To address the urgent need for safe food allergen immunotherapy, we have developed a liver-targeting nanoparticle platform, capable of intervening in allergic inflammation, mast cell release and anaphylaxis through the generation of regulatory T-cells (Treg). In this communication, we demonstrate the use of a poly (lactide-co-glycolide acid) (PLGA) nanoparticle platform for intervening in peanut anaphylaxis through the encapsulation and delivery of a dominant protein allergen, Ara h 2 and representative T-cell epitopes, to liver sinusoidal endothelial cells (LSECs). These cells have the capacity to act as natural tolerogenic antigen-presenting cells (APC), capable of Treg generation by T-cell epitope presentation by histocompatibility (MHC) type II complexes on the LSEC surface. This allowed us to address the hypothesis that the tolerogenic nanoparticles platform could be used as an effective, safe, and scalable intervention for suppressing anaphylaxis to crude peanut allergen extract. Following the analysis of purified Ara h 2 and representative MHC-II epitopes Treg generation in vivo, a study was carried out to compare the best-performing Ara h 2 T-cell epitope with a purified Ara h 2 allergen, a crude peanut protein extract (CPPE) and a control peptide in an oral sensitization model. Prophylactic as well as post-sensitization administration of the dominant encapsulated Ara h 2 T-cell epitope was more effective than the purified Ara h2 in eliminating anaphylactic manifestations, hypothermia, and mast cell protease release in a frequently used peanut anaphylaxis model. This was accompanied by decreased peanut-specific IgE blood levels and increased TGF-β release in the abdominal cavity. The duration of the prophylactic effect was sustained for two months. These results demonstrate that targeted delivery of carefully selected T-cell epitopes to natural tolerogenic liver APC could serve as an effective platform for the treatment of peanut allergen anaphylaxis.

Keywords: Ara h2 T-cell epitope; Peanut allergy; anaphylaxis; immunotherapy; liver-targeting; tolerogenic nanoparticle.

Grants and funding

U01 ES027237/ES/NIEHS NIH HHS/United States