Modulation of cellular, molecular, and humoral responses by PQ Grass 27,600 SU for the treatment of seasonal allergic rhinitis: a randomised double blind placebo control exploratory field study
Author(s)
Type
Journal Article
Abstract
Background:
A short-course pre-seasonal subcutaneous injection of PQ Grass is clinically effective for the treatment of allergic rhinitis, though its mechanism remains unclear. The aim of the study was to interrogate immunological mechanisms induced by PQ Grass conventional and extended regimens.
Methods:
A RDBPC exploratory field study involving participants that either received injections of PQ Grass with a cumulative dose of 27,600 SU conventional (six once weekly injections) or extended regimen (three once weekly injections followed by three once monthly injections) or placebo containing microcrystalline tyrosine (MCT) (placebo + MCT) or saline (placebo) was performed. Humoral, cellular, and molecular responses were assessed at baseline (V1), end of treatment, prior to grass pollen season (V12) and end of pollen season (V15). Immunoglobulin analyses and cellular/gene microarray analyses were performed in the sub-study cohort consisting of PQ Grass Conventional (n = 25 and n = 10, respectively), PQ Grass Extended (n = 26 and n = 10, respectively), Placebo with MCT (n = 13 and n = 5, respectively), and Placebo (saline; n = 12 and n = 5, respectively).
Results:
Both PQ Grass regimens, conventional and extended, were associated with improvement in total combined scores (TCS) with a relative difference of −35.0% (p = 0.03) and −40.8% (p = 0.01) against placebo with MCT, respectively. Both PQ Grass treatment regimens were associated with increases in the sIgG4/sIgE ratio (all, p < 0.05) and induction of IgA1 (all, p < 0.05) and IgA2 (all, p < 0.01) compared to placebo groups. Nasal fluid (p < 0.01) and serum (p < 0.05) blocking antibodies are functional and have the capacity to inhibit allergen-IgE complex formation and binding to B cells in the PQ Grass groups. In vitro cellular and microarray gene analyses demonstrated that the extended PQ Grass regimen was more proficient in modulating the immune response towards a tolerogenic milieu by dampening pro-inflammatory type 2 immune response and the associated cytokines (p < 0.05), immune deviation towards a Th1 response (p < 0.05), and induction of FOXP3+ Treg cells (p < 0.05).
Conclusions:
For the first time, we highlight differential mechanisms of tolerance induction by PQ Grass, with the extended regimen being superior in modulating T cell compartments.
Trail Registration:
Trial number: PQGrass309, EudraCT number: 2020-000408-13, Clinicaltrials.gov identifier: NCT04687059, and NCT05540717
A short-course pre-seasonal subcutaneous injection of PQ Grass is clinically effective for the treatment of allergic rhinitis, though its mechanism remains unclear. The aim of the study was to interrogate immunological mechanisms induced by PQ Grass conventional and extended regimens.
Methods:
A RDBPC exploratory field study involving participants that either received injections of PQ Grass with a cumulative dose of 27,600 SU conventional (six once weekly injections) or extended regimen (three once weekly injections followed by three once monthly injections) or placebo containing microcrystalline tyrosine (MCT) (placebo + MCT) or saline (placebo) was performed. Humoral, cellular, and molecular responses were assessed at baseline (V1), end of treatment, prior to grass pollen season (V12) and end of pollen season (V15). Immunoglobulin analyses and cellular/gene microarray analyses were performed in the sub-study cohort consisting of PQ Grass Conventional (n = 25 and n = 10, respectively), PQ Grass Extended (n = 26 and n = 10, respectively), Placebo with MCT (n = 13 and n = 5, respectively), and Placebo (saline; n = 12 and n = 5, respectively).
Results:
Both PQ Grass regimens, conventional and extended, were associated with improvement in total combined scores (TCS) with a relative difference of −35.0% (p = 0.03) and −40.8% (p = 0.01) against placebo with MCT, respectively. Both PQ Grass treatment regimens were associated with increases in the sIgG4/sIgE ratio (all, p < 0.05) and induction of IgA1 (all, p < 0.05) and IgA2 (all, p < 0.01) compared to placebo groups. Nasal fluid (p < 0.01) and serum (p < 0.05) blocking antibodies are functional and have the capacity to inhibit allergen-IgE complex formation and binding to B cells in the PQ Grass groups. In vitro cellular and microarray gene analyses demonstrated that the extended PQ Grass regimen was more proficient in modulating the immune response towards a tolerogenic milieu by dampening pro-inflammatory type 2 immune response and the associated cytokines (p < 0.05), immune deviation towards a Th1 response (p < 0.05), and induction of FOXP3+ Treg cells (p < 0.05).
Conclusions:
For the first time, we highlight differential mechanisms of tolerance induction by PQ Grass, with the extended regimen being superior in modulating T cell compartments.
Trail Registration:
Trial number: PQGrass309, EudraCT number: 2020-000408-13, Clinicaltrials.gov identifier: NCT04687059, and NCT05540717
Date Issued
2026-01-01
Date Acceptance
2025-04-19
Citation
Allergy, 2026, 81 (1), pp.232-247
ISSN
0105-4538
Publisher
Wiley
Start Page
232
End Page
247
Journal / Book Title
Allergy
Volume
81
Issue
1
Copyright Statement
© 2025 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
10.1111/all.16640
Subjects
This work was supported by Allergy Therapeutics allergy treament | basic mechanisms | immune tolerance | immunotherapy and tolerance induction | immunotherapy clinical | immunotherapy vaccines and mechanisms | T cells AIT, allergen immunotherapy
AR, allergic rhinitis
BAT, Basophil activation test
Breg, B regulatory cells
CPT, conjunctival provocation test
CSMS, combined symptom and medication score
dMS, daily medication score
dSS, daily symptom score
ELISA, enzyme linked immunosorbent assay
GPS, grass pollen season
IL, interleukin
MC, metacluster
MCT, microcrystalline tyrosine
MPL, monophosphoryl Lipid-A
PBMC, peripheral blood mononuclear cells
RDBPC, randomised double blind placebo control studies
SAR, seasonal allergic rhinitis
SCIT, subcutaneous immunotherapy
sIgA 1 , specific immunoglobulin A 1
sIgA 2 , specific immunoglobulin A 2
sIgG 4 , specific immunoglobulin G 4
SLIT, sublingual immunotherapy
SOM, self-organising maps
SU, standardised unit
TCS, total combined score
Tfh, T follicular helper cells
Th2, T helper 2 cells
Th2A, allergen-specific Th2 cells
Treg, T regulatory cells
TSS, total symptom score
Publication Status
Published
Article Number
all.16640
Date Publish Online
2025-07-08