Two grass pollen tablets commercially available for allergy immunotherapy display different IgE epitope repertoires

Abstract

Background The distribution of Pooideae species varies across Europe. Especially, Timothy is less represented in Southern than in Northern Europe. Since allergenic cross-reactivity between pollens from different grasses is only partial, grass pollen-allergic patients are expected to display different sensitization profiles, with specific IgE directed against different combinations of allergenic epitopes, depending on their living places in Europe and the grasses they are exposed to. In this context, this study aimed at comparing two tablets commercially available for allergy immunotherapy, namely a 5-grass (Cocksfoot, Meadow-grass, Rye-grass, Sweet vernal-grass and Timothy) and a 1-grass (Timothy) pollen tablets, for their ability to represent the sensitization profiles of patients, depending on whether they live in Southern or Northern Europe. Methods Sera were collected from adult patients living in Spain (n = 19) and Sweden (n = 22). Tablets were compared for their ability to inhibit the binding of patient serum IgE to pollen allergens from twelve grasses commonly distributed throughout Europe, as determined by the areas under the curves obtained by ELISA-inhibition. Tablets were adjusted to an equivalent allergenic activity, based on the CBER/FDA bioequivalent allergy unit. Results Inhibition of the IgE binding to pollen allergens from twelve grasses was significantly stronger with the 5-grass than with the 1-grass pollen tablet ( p < 0.0001), regardless of whether patients were considered as a whole or by geographical area. This difference between tablets was significantly greater for Southern than Northern European patients ( p < 0.05). Conclusions Compared to the 1-grass tablet, the 5-grass tablet generally covers better the sensitization profiles of European patients, especially patients from Southern Europe, in principle less exposed to pollen from Timothy than from other grasses. The 5-grass tablet is therefore expected to elicit larger spectra of blocking antibodies, which might have implications in light of the generally accepted mechanisms of allergy immunotherapy. Electronic supplementary material The online version of this article (10.1186/s13601-019-0253-z) contains supplementary material, which is available to authorized users.

Clinical efficacy of sublingual immunotherapy tablets for allergic rhinitis is unlikely to be derived from in vitro allergen-release data

“…This difference between SLIT tablets was significantly greater for Spanish than Swedish patients (p < 0.05). Fewer epitopes associated with grass pollen allergy were present in the 1-grass pollen SLIT tablet, compared with the 5-grass pollen SLIT tablet, and this difference was especially pronounced when comparing sera from patients in the two geographical regions [20]. In agreement with previous research [22], the authors concluded that the 5-grass pollen SLIT tablet has superior epitope coverage to the 1-grass pollen SLIT tablet, especially for patients from Spain and other Southern European countries, who may be less exposed to Timothy grass than other grass species [20].…”

“…Clinical onset of action [40] Not determined 1 month Grass pollen epitope coverage [20] + +++++ Efficacy in clinical trials [40] +++ +++ Safety in clinical trials [40] +++* +++ *Epinephrine was administered during clinical trials of the 1-grass pollen SLIT tablet [n = 1 adult receiving placebo, n = 1 adult receiving 1-grass pollen SLIT tablet (both cases judged as treatment-related) and n = 2 pediatric subjects (of which 1 case was judged as treatment-related)] [40]. BAU, bioequivalent allergy unit; IR, index of reactivity; SLIT, sublingual immunotherapy; SQ-T, standardized quality tablet unit grasses differs between countries [20,21]. The pollen allergens from different Pooideae species exhibit some shared T and B cell epitopes, while group 1 and group 5 allergens display species-restricted IgE epitopes [22].…”

“…The heterogeneity in grass pollen epitopes across species can be differentiated by the immune system, which may support the use of a mixed pollen allergen extract over a single pollen allergen preparation [21]. The ability of the 5-and 1-grass pollen SLIT tablets to mimic the range of epitopes that may be encountered in Europe has been assessed by testing sera from adult patients living in Spain (n = 19) or Sweden (n = 22) [20]. The 5-grass pollen SLIT tablet demonstrated significantly greater inhibition of IgE binding to pollen allergens from 12 grasses common to Europe (bent grass, Bermuda grass, brome grass, cocksfoot, false oat-grass, meadow fescue, meadowgrass, rye-grass, sweet vernal-grass, timothy, wild oat and Yorkshire fog) than did the 1-grass pollen SLIT tablet (p < 0.0001), both for the total tested population and when stratified by country.…”

Highlights and recent developments in allergic diseases in EAACI journals (2019)

“…Two grass pollen tablets commercially available for allergy immunotherapy display different IgE epitope repertoires [ 102 ]. Compared to the 1-grass tablet, the 5-grass tablet generally covers better the sensitization profiles of European patients, especially patients from Southern Europe, in principle less exposed to pollen from Timothy than from other grasses.…”

GRAZAX®: a sublingual immunotherapy vaccine for Hay fever treatment: from concept to commercialization

“…49 Recently, it has been shown that some patients, mostly resident in the south of Europe, could have a higher sIgE recognition to a five species vaccine. 50 Currently, there is no evidence of clinical superiority in base to the number of grass species included in the vaccine composition.…”