A Single Monoclonal Antibody against the Peanut Allergen Ara h 2 Protects against Systemic and Local Peanut Allergy

Abstract

Background: Peanut allergy is the most prevalent and dangerous food allergy. Peanuts consist of a large number of different allergens and peanut-allergic patients are frequently sensitized to multiple allergens. Hence, conventional desensitization approaches aim at targeting as many allergens as possible. Methods: The monoclonal anti-Ara h 2 antibody (mAb) was produced by hybridoma cells derived from WT BALB/c mice after immunization with a vaccine based on virus-like particles coupled to Ara h 2. BALB/c mice were sensitized intraperitoneally with peanut extract absorbed to alum and mAbs were applied i.v. Challenge was performed the next day with the whole peanut extract intravenously and via skin prick test. Results: Here we show in peanut-allergic mice that a single high-affinity mAb specific for Ara h 2 is able to block systemic and local allergic reactions induced by the complex peanut extract. We confirm in vitro binding of the mAb to the inhibitory low-affinity FcγRIIb receptor using a sensitive biosensor and demonstrate in vivo that protection was dependent on FcγRIIb. Conclusion: A single mAb specific for Ara h 2 is able to improve local and systemic allergic symptoms induced by the whole allergen mixture.

On the role of antibody affinity in the IgE mediated allergic response

“…Even though mice were allergic against multiple peanut allergens, immunization against a single allergen was sufficient to block allergic responses. Furthermore, polyclonal antibodies against Ara h 1 or Ara h2, as well as a mAb against Ara h 2 were able to abrogate allergic responses induced the peanut extract 25 , confirming earlier data for allergy against Fel d 1 , an allergy which is, however, mostly driven by a single allergen 26 . This protective effect of Ara h 1 and Ara h 2 antibodies was again strictly dependent on the presence of functional FcγRIIb.…”

Low‐affinity but high‐avidity interactions may offer an explanation for IgE‐mediated allergen cross‐reactivity

“…In support of this concept, we have recently shown that IgG antibodies with even surprisingly low affinity for the allergen are able to block mast cell activation by engaging the inhibitory FcγRIIb 19 . Furthermore, murine models demonstrated that polyclonal 18 and monoclonal 17 antibodies specific for a single allergen of peanut (Ara h 2) were able to block allergic symptoms mediated by the whole extract.…”

“…Even though there is an ongoing discussion about the most critical effector mechanism(s) responsible for this state of enhanced ‘tolerance’, it is clear that induction of allergen‐specific IgG correlates with reduced symptoms and is taken as evidence for successful therapy 12–14 . Furthermore, passive transfer of allergen‐specific IgG antibodies results in protection against allergic reactions both in preclinical and clinical settings 14–18 . In support of this concept, we have recently shown that IgG antibodies with even surprisingly low affinity for the allergen are able to block mast cell activation by engaging the inhibitory FcγRIIb 19 .…”

Virus-like particle vaccinology, from bench to bedside

“…These results demonstrate that vaccination against a single allergen can confer protection against challenge with a complex allergen mixture. Antibodies were established as the mode of action, as passive transfer of purified IgG or even a single monoclonal anti-Ara h 2 antibody conferred protection against allergic reactions in mice [91,92]. The role of the Fc γ RIIb receptor Fig.…”