D2.191 - Tolerogenic Immune Shifts Following PQ Grass 27600 SU Treatment in Seasonal Allergic Rhinitis

A pre-seasonal regimen of six subcutaneous injections of PQ Grass 27,600 SU has been shown to be an effective and well-tolerated treatment for seasonal allergic rhinitis. In this study, we investigated the tolerogenic mechanisms of PQ Grass, focusing on the induction of functional blocking antibodies and modulation of T-cell responses.

In vitro mechanistic analyses were conducted using samples from subjects who received either PQ Grass (n = 40) or placebo (n = 35) across two clinical trials (PQG309 and PQG306). Peripheral blood mononuclear cells (PBMCs) and serum were collected at baseline (pre-treatment), post-treatment prior to the grass pollen season (pre-season), and after the pollen season (post-season). Allergen-specific IgG, IgG4, IgA1, and IgA2 levels were quantified using ImmunoCAP 200, and antibody functionality was evaluated using the IgE-facilitated allergen binding (IgE-FAB) assay. PQ Grass-induced modulation of T-cell responses was assessed by multiparametric flow cytometry.

Combined Symptom Medication Score [CSMS_0-6], measured as the primary endpoint, from both trials demonstrated statistically significant improvement of −22.5% (P<0.00004) compared to placebo. Across both trials, PQ Grass was associated with a systemic induction of grass pollen-specific IgG (both, P<0.001), sIgG4 (both, P<0.001), sIgA1 (both, P<0.001) and sIgA2 (both, P<0.01) compared to placebo, pre- and post-season. Functionally, serum from PQ Grass-treated participants exhibited enhanced blocking activity, significantly inhibiting allergen–IgE complex binding to B cells at both pre-season (P<0.001) and post-season (P<0.01) time points relative to placebo. Blocking antibody levels showed a strong correlation with IgE-FAB responses. At the cellular level, PQ Grass treatment resulted in significantly reduced grass pollen–induced proliferation of Th2 and Th2A cells compared with placebo (both P<0.05). A trend toward reduced proliferation of T follicular helper (Tfh) and IL-21⁺ Tfh cells in response to grass pollen allergen was also observed in PQ Grass-treated participants. In addition, a positive trend toward increased induction of memory regulatory T cells (Tregs) was noted in the PQ Grass group compared with placebo.

PQ Grass is an effective treatment for seasonal allergic rhinitis and promotes a favourable tolerogenic immune profile through coordinated modulation of both humoral and cellular immune responses.