Development of a novel Ara h 2 hypoallergen with no IgE binding or anaphylactogenic activity

Abstract

Background: To date, no safe allergen-specific immunotherapy for patients with peanut allergy is available. Previous trials were associated with severe side effects. Objective: We sought to determine the relative importance of conformational and linear IgE-binding epitopes of the major peanut allergen Ara h 2 and to produce a hypoallergenic variant with abolished anaphylactogenic activity. Methods: Wild-type Ara h 2 and a mutant lacking the loops containing linear IgE epitopes were produced in insect cells. Conformational IgE epitopes were removed by unfolding these From a

Past, present, and future of allergen immunotherapy vaccines

“…25 Furthermore, preclinical studies demonstrate that hypoallergens induce blocking IgG antibodies and can be developed for many respiratory, venom, and also food allergens. [133][134][135][136][137] In fact, recent results of a I/ IIa phase double-blind, placebo-controlled clinical study (Identifier: should be mentioned. 142 As recombinant Alt a 1 was found to be equivalent with natural Alt a 1 one may assume that this could have been equally achieved with purified rAlt a 1.…”

Dynamics Rationalize Proteolytic Susceptibility of the Major Birch Pollen Allergen Bet v 1

“…Still, the determinants of what makes a protein an allergen are largely unknown (Scheurer et al, 2015;Verhoeckx et al, 2019). It has been demonstrated repeatedly that proteins with substantial similarity in sequence and structure are able to trigger an entirely different immune response (Mitropoulou et al, 2018;Eichhorn et al, 2019;Seutter von Loetzen et al, 2019;Tscheppe et al, 2020). Thus, the allergenic potential of a protein often cannot be rationalized, nor predicted, based on sequence or structural similarity to known allergens (Lu et al, 2018).…”

Advances and novel developments in molecular allergology

“…The fusion of Bet v 1 and Phl p 5 is such an example, which altered their biophysical characteristics and impaired their IgE cross‐linking ability 77 . Otherwise, destruction of both linear and conformational epitopes of Ara h 2, 78,79 and Ara h 6 79 resulted in retained T‐cell stimulation capacity while abolishing the IgE binding.…”