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Products: Peanuts
Subject: Allergy
Ara h 2-expressing cucumber mosaic virus-like particle (VLP Peanut) induces in vitro tolerogenic cellular responses in peanut-allergic individuals
Authors: Layhadi, J. A., Starchenka, S., De Kam, P. J., Palmer, E., Patel, N., Keane, S. T., Hikmawati, P., Drazdauskaite, G., Wu, L. Y. D., Filipaviciute, P., Parkin, R. V., Oluwayi, K., Rusyn, O., Skinner, M. A., Heath, M. D., Hewings, S. J., Kramer, M. F., Turner, P., & Shamji, M. H.
- Journals: Journal of Allergy and Clinical Immunology
- Pages: 153–165
- Volume: 155(1)
- Year: 2025
Background: Peanut allergy (PA) is one of the most prevalent food allergies with a lack of favorable safety/efficacy treatment. A cucumber mosaic virus-like particle expressing peanut allergen component Ara h 2 (VLP Peanut) has been developed as a novel therapeutic approach for PA. Objective: We assessed the tolerogenic properties and reactivity of VLP Peanut. Methods: Whole blood and peripheral blood mononuclear cells were collected from 6 peanut-allergic children. Modulation of dendritic cells (DCs), T cells, and B cells, stimulated with VLP Peanut, Ara h 2, and whole peanut extract in vitro, were assessed by quantitative real-time PCR and flow cytometry, respectively. Basophil and skin reactivity in response to VLP Peanut was assessed by basophil activation test and skin prick test, respectively. Results: VLP Peanut showed beneficial biochemical properties, fit for use in clinical studies. VLP Peanut induced IFN-γ+ TH1 (P < .05) while having reduced capacity to elicit proliferation of TH2, allergen-specific TH2, and IL-4+-T follicular helper cells. Moreover, VLP Peanut is associated with upregulation of DC1-associated genes (MX1) compared to Ara h 2 and whole peanut extract. VLP Peanut was the most prominent at inducing IL-10+ regulatory B cells (P < .05). Unbiased clustering analyses identified metaclusters of T and B cells targeted by VLP Peanut. Finally, VLP Peanut had reduced capacity to elicit high- and low-affinity IgE receptor-mediated responses compared to Ara h 2 or whole peanut extract (all P < .05). Finally, in an open-label first-in-human cohort of 6 peanut-allergic adults, administration of increasing concentration of VLP Peanut through skin prick test was tolerated and demonstrated no development of skin reactivity. Conclusions: VLP Peanut displayed tolerogenic properties by modulating DCs, T cells, and B cells in vitro. Preliminary findings of skin reactivity using VLP Peanut in 6 peanut-allergic adults was safe and well tolerated in an open-label phase 1 study.
https://doi.org/10.1016/j.jaci.2024.08.010
https://doi.org/10.1016/j.jaci.2024.08.010