Modulation of Cellular, Molecular, and Humoral Responses by PQ Grass 27,600 SU for the Treatment of Seasonal Allergic...

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.

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).

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).

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.

Trial number: PQGrass309, EudraCT number: 2020-000408-13, Clinicaltrials.gov identifier: NCT04687059, and NCT05540717.