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Clinical Trial
. 2019 Sep;144(3):738-749.
doi: 10.1016/j.jaci.2019.02.023. Epub 2019 Mar 5.

Immunologic mechanisms of a short-course of Lolium perenne peptide immunotherapy: A randomized, double-blind, placebo-controlled trial

Hanisah Sharif  1 , Iesha Singh  1 , Lubna Kouser  1 , Ralph Mösges  2 , Marie-Alix Bonny  3 , Angeliki Karamani  1 , Rebecca V Parkin  1 , Nicolas Bovy  3 , Uday Kishore  4 , Abigail Robb  1 , Michael Katotomichelakis  5 , Gabriële Holtappels  5 , Lara Derycke  5 , Francis Corazza  6 , Rémy von Frenckell  7 , Nathalie Wathelet  3 , Jean Duchateau  3 , Thierry Legon  3 , Sabine Pirotton  3 , Stephen R Durham  1 , Claus Bachert  5 , Mohamed H Shamji  8
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Free article
Clinical Trial

Immunologic mechanisms of a short-course of Lolium perenne peptide immunotherapy: A randomized, double-blind, placebo-controlled trial

Hanisah Sharif et al. J Allergy Clin Immunol. 2019 Sep.
Free article

Abstract

Background: A 3-week short-course of adjuvant-free hydrolysates of Lolium perenne peptide (LPP) immunotherapy for rhinoconjunctivitis with or without asthma over 4 physician visits is safe, well tolerated, and effective.

Objective: We sought 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.govNCT02560948).

Methods: Participants were randomized to receive LPP (n = 21) or placebo (n = 11) for 3 weeks over 4 visits. Grass pollen-induced basophil, T-cell, and B-cell responses were evaluated before treatment (visit [V] 2), at the end of treatment (V6), and after the pollen season (V8).

Results: Combined symptom and rescue medication scores (CSMS) were lower during the peak pollen season (-35.1%, P = .03) and throughout the pollen season (-53.7%, P = .03) in the LPP-treated group compared with those in the placebo-treated group. Proportions of CD63+ and CD203cbrightCRTH2+ basophils were decreased following LPP treatment at V6 (10 ng/mL, P < .0001) and V8 (10 ng/mL, P < .001) compared to V2. No change in the placebo-treated group was observed. Blunting of seasonal increases in levels of grass pollen-specific IgE was observed in LPP-treated but not placebo-treated group. LPP immunotherapy, but not placebo, was associated with a reduction in proportions of IL-4+ TH2 (V6, P = .02), IL-4+ (V6, P = .003; V8, P = .004), and IL-21+ (V6, P = .003; V8, P = .002) follicular helper T cells. Induction of FoxP3+, follicular regulatory T, and IL-10+ regulatory B 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 immunologic mechanisms of LPP immunotherapy are underscored by immune modulation in the T- and B-cell compartments, which is necessary for its effect.

Keywords: Allergy; follicular helper T cells; peptide immunotherapy; regulatory B cells; regulatory T cells.

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