Fel d 1‐expressing plant‐derived bioparticle: a novel treatment for cat allergy
Author(s)
Type
Journal Article
Abstract
Background
Allergen immunotherapy (AIT) is the only disease-modifying therapeutic approach for cat allergy, though it requires at least three years of treatment and can potentially induce severe systemic reactions. Plant-derived bioparticles expressing Fel d 1 allergen (Fel d 1 eBP) have been developed as a novel therapeutic candidate for cat allergy. We aimed to investigate the allergenicity and immunogenicity profile of Fel d 1 eBP.
Methods
Fel d 1 eBP was synthesised in vivo in Nicotiana benthamiana and confirmed by cryo-electron microscopy and tomography. Immune modulatory properties of purified natural Fel d 1 (nFel d 1) and Fel d 1 eBP were assessed at T and B cells by flow cytometry in 12 cat-allergic subjects (CA) and 12 non-atopic controls (NAC). Single-cell RNA-seq was used to assess molecular mechanisms of Fel d 1 eBP immune skewing. The safety of Fel d 1 eBP was assessed by measuring basophil responsiveness in whole blood and further confirmed in vivo by its administration as a skin prick test (SPT) in 20 cat-allergic individuals.
Results
Fel d 1 eBP was shown to be a strong inducer of Th1 cells (p < 0.05) and IL-10+ non-Th2 cells (p < 0.05) in CA subjects. Fel d 1 eBP showed a stronger trend for inducing IL-10+ Breg cells compared to nFel d 1, peaking at 3 μg/mL. scRNA-seq analyses demonstrated that Fel d 1 eBP targets the induction of protective metallothionein genes, CCL18+ monocytes and naïve B cells that are interferon responsive and metabolically activated. Moreover, Fel d 1 eBP demonstrated reduced capacity to elicit basophil activation (p < 0.001) and histamine release (p < 0.01), indicating their hypoallergenic nature. Administration of titrated doses of Fel d 1 eBP through skin prick test revealed that they are well-tolerated with reduced mean wheal compared to native Fel d 1 in an open-label Phase 0 study (all, p < 0.001).
Conclusions
We demonstrate that Fel d 1 eBP is hypoallergenic and demonstrates tolerogenic properties, making it a novel candidate for use in AIT for cat allergy.
Allergen immunotherapy (AIT) is the only disease-modifying therapeutic approach for cat allergy, though it requires at least three years of treatment and can potentially induce severe systemic reactions. Plant-derived bioparticles expressing Fel d 1 allergen (Fel d 1 eBP) have been developed as a novel therapeutic candidate for cat allergy. We aimed to investigate the allergenicity and immunogenicity profile of Fel d 1 eBP.
Methods
Fel d 1 eBP was synthesised in vivo in Nicotiana benthamiana and confirmed by cryo-electron microscopy and tomography. Immune modulatory properties of purified natural Fel d 1 (nFel d 1) and Fel d 1 eBP were assessed at T and B cells by flow cytometry in 12 cat-allergic subjects (CA) and 12 non-atopic controls (NAC). Single-cell RNA-seq was used to assess molecular mechanisms of Fel d 1 eBP immune skewing. The safety of Fel d 1 eBP was assessed by measuring basophil responsiveness in whole blood and further confirmed in vivo by its administration as a skin prick test (SPT) in 20 cat-allergic individuals.
Results
Fel d 1 eBP was shown to be a strong inducer of Th1 cells (p < 0.05) and IL-10+ non-Th2 cells (p < 0.05) in CA subjects. Fel d 1 eBP showed a stronger trend for inducing IL-10+ Breg cells compared to nFel d 1, peaking at 3 μg/mL. scRNA-seq analyses demonstrated that Fel d 1 eBP targets the induction of protective metallothionein genes, CCL18+ monocytes and naïve B cells that are interferon responsive and metabolically activated. Moreover, Fel d 1 eBP demonstrated reduced capacity to elicit basophil activation (p < 0.001) and histamine release (p < 0.01), indicating their hypoallergenic nature. Administration of titrated doses of Fel d 1 eBP through skin prick test revealed that they are well-tolerated with reduced mean wheal compared to native Fel d 1 in an open-label Phase 0 study (all, p < 0.001).
Conclusions
We demonstrate that Fel d 1 eBP is hypoallergenic and demonstrates tolerogenic properties, making it a novel candidate for use in AIT for cat allergy.
Date Issued
2026-06-01
Date Acceptance
2026-02-07
Citation
Allergy, 2026, 81 (6), pp.2156-2171
ISSN
0105-4538
Publisher
Wiley
Start Page
2156
End Page
2171
Journal / Book Title
Allergy
Volume
81
Issue
6
Copyright Statement
© 2026 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/41856757
Subjects
allergen immunotherapy
allergy
cat allergy
tolerance induction
Publication Status
Published
Coverage Spatial
Denmark
Date Publish Online
2026-03-19