Janice A Layhadi, Sviatlana Starchenka, Pieter-Jan De Kam, Elizabeth Palmer, Nandinee Patel, Sean T Keane, Prista Hikmawati, Gabija Drazdauskaite, Lily Y D Wu, Paulina Filipaviciute, Rebecca V Parkin, Kemi Oluwayi, Olesya Rusyn, Murray A Skinner, Matthew D Heath, Simon J Hewings, Matthias F Kramer, Paul Turner, Mohamed H Shamji
{"title":"表达a2的黄瓜花叶病毒样颗粒（VLP花生）诱导花生过敏个体的体外耐受性细胞反应。","authors":"Janice A Layhadi, Sviatlana Starchenka, Pieter-Jan De Kam, Elizabeth Palmer, Nandinee Patel, Sean T Keane, Prista Hikmawati, Gabija Drazdauskaite, Lily Y D Wu, Paulina Filipaviciute, Rebecca V Parkin, Kemi Oluwayi, Olesya Rusyn, Murray A Skinner, Matthew D Heath, Simon J Hewings, Matthias F Kramer, Paul Turner, Mohamed H Shamji","doi":"10.1016/j.jaci.2024.08.010","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>We assessed the tolerogenic properties and reactivity of VLP Peanut.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>VLP Peanut showed beneficial biochemical properties, fit for use in clinical studies. VLP Peanut induced IFN-γ<sup>+</sup> T<sub>H</sub>1 (P < .05) while having reduced capacity to elicit proliferation of T<sub>H</sub>2, allergen-specific T<sub>H</sub>2, and IL-4<sup>+</sup>-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<sup>+</sup> 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.</p><p><strong>Conclusions: </strong>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.</p><p><strong>Clinical trial identifier: </strong>PROTECT, NCT05476497.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 1","pages":"153-165"},"PeriodicalIF":11.4000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Ara h 2-expressing cucumber mosaic virus-like particle (VLP Peanut) induces in vitro tolerogenic cellular responses in peanut-allergic individuals.\",\"authors\":\"Janice A Layhadi, Sviatlana Starchenka, Pieter-Jan De Kam, Elizabeth Palmer, Nandinee Patel, Sean T Keane, Prista Hikmawati, Gabija Drazdauskaite, Lily Y D Wu, Paulina Filipaviciute, Rebecca V Parkin, Kemi Oluwayi, Olesya Rusyn, Murray A Skinner, Matthew D Heath, Simon J Hewings, Matthias F Kramer, Paul Turner, Mohamed H Shamji\",\"doi\":\"10.1016/j.jaci.2024.08.010\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>We assessed the tolerogenic properties and reactivity of VLP Peanut.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>VLP Peanut showed beneficial biochemical properties, fit for use in clinical studies. VLP Peanut induced IFN-γ<sup>+</sup> T<sub>H</sub>1 (P < .05) while having reduced capacity to elicit proliferation of T<sub>H</sub>2, allergen-specific T<sub>H</sub>2, and IL-4<sup>+</sup>-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<sup>+</sup> 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.</p><p><strong>Conclusions: </strong>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.</p><p><strong>Clinical trial identifier: </strong>PROTECT, NCT05476497.</p>\",\"PeriodicalId\":14936,\"journal\":{\"name\":\"Journal of Allergy and Clinical Immunology\",\"volume\":\"155 1\",\"pages\":\"153-165\"},\"PeriodicalIF\":11.4000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Allergy and Clinical Immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jaci.2024.08.010\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ALLERGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Allergy and Clinical Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jaci.2024.08.010","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ALLERGY","Score":null,"Total":0}
Ara h 2-expressing cucumber mosaic virus-like particle (VLP Peanut) induces in vitro tolerogenic cellular responses in peanut-allergic individuals.
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.
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The Journal of Allergy and Clinical Immunology is a prestigious publication that features groundbreaking research in the fields of Allergy, Asthma, and Immunology. This influential journal publishes high-impact research papers that explore various topics, including asthma, food allergy, allergic rhinitis, atopic dermatitis, primary immune deficiencies, occupational and environmental allergy, and other allergic and immunologic diseases. The articles not only report on clinical trials and mechanistic studies but also provide insights into novel therapies, underlying mechanisms, and important discoveries that contribute to our understanding of these diseases. By sharing this valuable information, the journal aims to enhance the diagnosis and management of patients in the future.
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