Ara h 2–expressing cucumber mosaic virus–like particle (VLP Peanut) induces in vitro tolerogenic cellular responses in peanut-allergic individuals
Janice A. Layhadi, Sviatlana Starchenka, Pieter‐Jan de Kam, Elizabeth Palmer, Nandinee Patel, Sean T. Keane, Prista Hikmawati, Gabija Drazdauskaitė, Lily Y.D. Wu, Paulina Filipaviciute, Rebecca Parkin, Kemi Oluwayi, Olesya Rusyn, Murray Skinner, Matthew D. Heath, Simon Hewings, Matthias Krämer, Paul Turner, Mohamed H. Shamji
Abstract
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: 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. CLINICAL TRIAL IDENTIFIER: PROTECT, NCT05476497.