{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T16:33:07Z","timestamp":1787157187603,"version":"build-2736575974"},"reference-count":76,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Allergen immunotherapy (AIT) is the only disease\u2010modifying therapeutic approach for cat allergy, though it requires at least three years of treatment and can potentially induce severe systemic reactions. Plant\u2010derived bioparticles expressing Fel d 1 allergen (Fel d 1\n                      <jats:italic>e<\/jats:italic>\n                      BP) have been developed as a novel therapeutic candidate for cat allergy. We aimed to investigate the allergenicity and immunogenicity profile of Fel d 1\n                      <jats:italic>e<\/jats:italic>\n                      BP.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Fel d 1\n                      <jats:italic>e<\/jats:italic>\n                      BP was synthesised in\u00a0vivo in\n                      <jats:italic>Nicotiana benthamiana<\/jats:italic>\n                      and confirmed by cryo\u2010electron microscopy and tomography. Immune modulatory properties of purified natural Fel d 1 (nFel d 1) and Fel d 1\n                      <jats:italic>e<\/jats:italic>\n                      BP were assessed at T and B cells by flow cytometry in 12 cat\u2010allergic subjects (CA) and 12 non\u2010atopic controls (NAC). Single\u2010cell RNA\u2010seq was used to assess molecular mechanisms of Fel d 1\n                      <jats:italic>e<\/jats:italic>\n                      BP immune skewing. The safety of Fel d 1\n                      <jats:italic>e<\/jats:italic>\n                      BP was assessed by measuring basophil responsiveness in whole blood and further confirmed in\u00a0vivo by its administration as a skin prick test (SPT) in 20 cat\u2010allergic individuals.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Fel d 1\n                      <jats:italic>e<\/jats:italic>\n                      BP was shown to be a strong inducer of Th1 cells (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05) and IL\u201010\n                      <jats:sup>+<\/jats:sup>\n                      non\u2010Th2 cells (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05) in CA subjects. Fel d 1\n                      <jats:italic>e<\/jats:italic>\n                      BP showed a stronger trend for inducing IL\u201010\n                      <jats:sup>+<\/jats:sup>\n                      Breg cells compared to nFel d 1, peaking at 3\u2009\u03bcg\/mL. scRNA\u2010seq analyses demonstrated that Fel d 1\n                      <jats:italic>e<\/jats:italic>\n                      BP targets the induction of protective metallothionein genes, CCL18\n                      <jats:sup>+<\/jats:sup>\n                      monocytes and na\u00efve B cells that are interferon responsive and metabolically activated. Moreover, Fel d 1\n                      <jats:italic>e<\/jats:italic>\n                      BP demonstrated reduced capacity to elicit basophil activation (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and histamine release (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01), indicating their hypoallergenic nature. Administration of titrated doses of Fel d 1\n                      <jats:italic>e<\/jats:italic>\n                      BP through skin prick test revealed that they are well\u2010tolerated with reduced mean wheal compared to native Fel d 1 in an open\u2010label Phase 0 study (all,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      We demonstrate that Fel d 1\n                      <jats:italic>e<\/jats:italic>\n                      BP is hypoallergenic and demonstrates tolerogenic properties, making it a novel candidate for use in AIT for cat allergy.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/all.70280","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T01:55:17Z","timestamp":1773971717000},"page":"2156-2171","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fel d 1\u2010Expressing Plant\u2010Derived Bioparticle: A Novel Treatment for Cat Allergy"],"prefix":"10.1111","volume":"81","author":[{"given":"Janice A.","family":"Layhadi","sequence":"first","affiliation":[{"name":"National Heart and Lung Institute Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana Cifuentes","family":"Gutierrez","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute Imperial College London  London UK"},{"name":"Royal Brompton Hospital, Guy's and St Thomas' NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean T.","family":"Keane","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2803-5008","authenticated-orcid":false,"given":"William","family":"Fulton","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nichell A.","family":"Samson","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lily Y. 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