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Mechanisms, safety and efficacy of a B cell epitope-based vaccine for immunotherapy of grass pollen allergy
AuthorValenta, Rudolf ; Henning, Rainer ; Horak, Friedrich ; Knoll, Anette ; Neubauer, Angela ; Huber, Hans ; Stolz, Frank ; Valent, Peter ; Blatt, Katharina ; Kiss, Renata ; Weber, Milena ; Zieglmayer, Rene ; Lemell, Patrick ; Schmutz, Rene ; Focke-Tejkl, Margarete ; Zieglmayer, Petra
Published in
EBioMedicine, Amsterdam, 2016, Vol. 11, page 43-57
PublishedAmsterdam : Elsevier, 2016
Document typeJournal Article
Keywords (EN)vaccine / grass pollen / b cell-epitope / challenge chamber / immunotherapy / monophosphoryl-lipid-a / blocking antibodies / immunoglobulin-e / ige / recombinant / responses / extracts / birch / rhinoconjunctivitis / microarray
Project-/ReportnumberF 4605-B28
URNurn:nbn:at:at-ubmuw:3-1674 Persistent Identifier (URN)
 The work is publicly available
Mechanisms, safety and efficacy of a B cell epitope-based vaccine for immunotherapy of grass pollen allergy [1.83 mb]
Abstract (English)

Background: We have developed a recombinant B cell epitope-based vaccine (BM32) for allergen-specific immunotherapy (AIT) of grass pollen allergy. The vaccine contains recombinant fusion proteins consisting of allergen-derived peptides and the hepatitis B surface protein domain preS as immunological carrier. Methods: We conducted a randomized, double-blind, placebo-controlled AIT study to determine safety, clinical efficacy and immunological mechanism of three subcutaneous injections of three BM32 doses adsorbed to aluminum-hydroxide versus aluminum hydroxide (placebo) applied monthly to grass pollen allergic patients (n=70). Primary efficacy endpoint was the difference in total nasal symptom score (TNSS) through grass pollen chamber exposure before treatment and 4 weeks after the last injection. Secondary clinical endpoints were total ocular symptom score (TOSS) and allergen-specific skin response evaluated by titrated skin prick testing (SPT) at the same time points. Treatment-related side effects were evaluated as safety endpoints. Changes in allergen-specific antibody, cellular and cytokine responses were measured in patients before and after treatment. Results: Sixty-eight patients completed the trial. TNSS significantly decreased with mean changes of -1.41 (BM32/20 mu g) (P=0.03) and -1.34 (BM32/40 mu g) (P=0.003) whereas mean changes in the BM32/10 mu g and placebo group were not significant. TOSS and SPT reactions showed a dose-dependent decrease. No systemic immediate type side effects were observed. Only few grade 1 systemic late phase reactions occurred in BM32 treated patients. The number of local injection site reactions was similar in actively and placebo-treated patients. BM32 induced highly significant allergen-specific IgG responses (P < 0.0001) but no allergen-specific IgE. Allergen-induced basophil activation was reduced in BM32 treated patients and addition of therapy-induced IgG significantly suppressed T cell activation (P=0.0063). Conclusion: The B cell epitope-based recombinant grass pollen allergy vaccine BM32 is well tolerated and few doses are sufficient to suppress immediate allergic reactions as well as allergen-specific T cell responses via a selective induction of allergen-specific IgG antibodies. (ClinicalTrials.gov number, NCT01445002.) (C) 2016 The Authors. Published by Elsevier B.V.

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