Targeting Ara h 2 with human‐derived monoclonal antibodies prevents peanut‐induced anaphylaxis in mice

Background Peanut allergy is a type‐I hypersensitivity immune reaction mediated by the binding of peanut allergens to IgE‐FcεRI complexes on mast cells and basophils and by their subsequent cellular degranulation. Of all major peanut allergens, Ara h 2 is considered the most anaphylactic. With few options but allergen avoidance, effective treatment of allergic patients is needed. Passive immunotherapy (herein called PIT) based on prophylactic administration of peanut‐specific monoclonal antibodies (mAbs) may present a promising treatment option for this under‐served disease. Method Fully human recombinant anti‐peanut IgG mAbs were tested in mice sensitized to peanut allergen extract. Allergic mice received intravenous immunotherapy with anti‐peanut Ara h 2‐specific IgG1 or IgG4 mAbs cocktails, and were then challenged by a systemic injection of high‐dose peanut allergen extract. The protection from allergic anaphylaxis was measured by monitoring the core body temperature. Results PIT with peanut‐specific mAbs was associated with a significant and dose‐dependent reduction of anaphylactic reactions in peanut‐sensitized mice challenged with peanut allergen extract. Complete protection was observed at doses approximately 0.3–0.6 mg mAbs. Mixtures of mAbs were more effective than single mAbs, and effective treatment could be obtained with mAbs of both IgG1 and IgG4 subclasses. The therapeutic effect of anti‐Ara h 2 mAbs was based on allergen neutralization and independent of the Fcγ receptor and mast‐cell inhibition. Conclusion This is the first report that shows that human‐derived anti‐peanut mAbs can prevent allergic anaphylaxis in mice. The study demonstrates that neutralizing allergenic epitopes on Ara h 2 by mAbs may represent a promising treatment option in peanut‐allergy. Anti‐Ara h 2 IgG1/IgG4 mAbs from peanut‐allergic patients were cloned and recombinantly produced. Preclinical testing was performed in peanut‐sensitized mice receiving passive immunotherapy prior to an allergen challenge. Anti‐Ara h 2 mAbs prevent allergic anaphylaxis by neutralizing peanut allergens before they bind to IgE and induce a FcɛRI‐mediated degranulation of mast cells and basophils.Abbreviations: AUC, area under the curve; FcɛRI, Fc epsilon receptor I; Ig, immunoglobulin; mAbs, monoclonal antibodies; PIT, passive immunotherapy; temp., temperature