Short-Term Preseasonal Immunotherapy: Is Early Clinical Efficacy Related to the Basophil Response?

Abstract

Background: An aluminum hydroxide-adsorbed depot allergoid preparation of six-grass pollen allergens has been developed for short-term preseasonal immunotherapy in pollinosis. However, only limited knowledge exists about its immunological and clinical effects. The aim of this study was to evaluate the basophil response, which can explain early clinical findings of short-term preseasonal allergoid immunotherapy in allergic rhinitis. Methods: In a double-blind, placebo-controlled study, 31 patients allergic to grass pollens received one course of short-term preseasonal allergoid immunotherapy or placebo. Immunogenicity was assessed by the levels of specific IgG4, IgE antibodies and an allergen-induced CD203c basophil activation test. The primary clinical end point was the combined symptom and medication score/average combined score (ACS). Results: There was a 52.9% difference in ACS between the treatment and placebo groups in favor of immunotherapy (p = 0.01). Active treatment induced Phleum pratense-specific IgG4 and IgE antibodies (p < 0.05). A decrease in allergen-induced basophil activation at submaximal allergen concentrations was demonstrated at the end of immunotherapy and at the peak of the grass pollen season after immunotherapy. Conclusions: This study shows that grass pollen-allergic patients treated with one course of short-term preseasonal allergoid immunotherapy exhibit a decrease in allergen-induced basophil activation, an increase in allergen-specific IgG4 antibodies and early clinical improvement.

Alum‐adjuvanted allergoids induce functional IgE‐blocking antibodies

“…Thus, preseasonal AIT with formaldehyde‐modified GP‐allergens induced IgG1‐ and IgG4‐antibodies specific for GP‐extract as well as for defined major grass allergens in our patient group, indicating—in line with previous studies—that this allergoid retains immunogenicity and at least part of the original, native Ig epitopes. Interestingly, the production of allergen‐specific IgG4 antibodies started later than the production of IgG1 in several patients and the drop at 12 months was less prominent.…”

“…Such antibodies in sera from patients receiving subcutaneous AIT with unmodified allergens have been reported to block IgE‐activity . It has been discussed that IgG antibodies induced by allergoids also have blocking capacity; however, their functional blocking capacity has not been demonstrated yet. We employed sera from patients allergic to grass pollen (GP) who were undergoing preseasonal AIT with an allergoid vaccine to investigate their IgE‐blocking capacity.…”

Recombinant Fusion Allergens, Cry j 1 and Cry j 2 from Japanese Cedar Pollen, Conjugated with Polyethylene Glycol Potentiate the Attenuation of Cry j 1-Specific IgE Production in Cry j 1-Sensitized Mice and Japanese Cedar Pollen Allergen-Sensitized Monkeys

“…In the two-group comparisons, the ratio of inhibition was significantly different between the 100-μg- and saline-treated groups by the unpaired Student t test (p < 0.05). The induction of inhibitory IgG may prevent IgE-facilitated antigen presentation by dendritic cells and B cells to antigen-specific Th2 cells and also prevent activation of basophils and mast cells after systematic challenge with Cry j 1 [15]. …”

Novel approaches and perspectives in allergen immunotherapy

“…These early changes in basophil sensitivity were shown to predict clinical outcome in the following pollen season and are maintained throughout maintenance therapy and even after treatment cessation . A protocol of preseasonal injections also reduced the basophil response .…”