Background

Three-week, short-course of adjuvant-free hydrolysates of Lolium perenne peptide (LPP) immunotherapy for rhinoconjunctivitis with/without asthma over 4 physician visits is safe, well-tolerated and effective.
Objective

To investigate immunologic mechanisms of LPP immunotherapy in a subset of patients who participated in a Phase III, multicenter, randomized, double-blind, placebo-controlled trial (clinical.gov NCT02560948).
Methods

Participants were randomized to receive LPP (n=21) or placebo (PL; n=11) for 3 weeks over 4 visits. Grass pollen-induced basophil, T and B cell responses were evaluated before (V2), end of treatment (V6) and after the pollen season (V8).
Results

Combined symptom and rescue medication scores (CSMS) were lower during the peak (-35.1%, P=.03) and throughout pollen season (-53.7%, P=.03) in LPP- compared to PL-treated group. CD63+ and CD203cbrightCRTH2+basophils were decreased following LPP treatment at V6 (all, P<.0001) and V8 (all, P<.001), compared to V2. No change in PL-treated group was observed. Blunting of seasonal increases of grass pollen-specific IgE was observed in LPP- but not PL-treated group. LPP immunotherapy but not PL was associated with a reduction of IL-4+ Th2 (V6, P=.02), IL-4+ (V6, P=.001;V8, P=.0095) and IL-21+ (V6, P=.0002) T follicular helper cells. Induction of FoxP3+, follicular regulatory T and IL-10+ Breg cells were observed at V6 (all, P<.05) and V8 (all, P<.05) in LPP-treated group. Induction of regulatory B cells was associated with allergen neutralizing IgG4 blocking antibodies.
Conclusion

For the first time, we demonstrate that the immunological mechanisms of LPP immunotherapy are underscored by immune modulation in the T and B cell compartments which is necessary for its effect.