Allergen immunotherapy: progress and future outlook.

INTRODUCTION: Allergy, the immunological hypersensitivity to innocuous environmental compounds, is a global health problem. The disease triggers, allergens, are mostly proteins contained in various natural sources such as plant pollen, animal dander, dust mites, foods, fungi, and insect venoms. Allergies can manifest with a wide range of symptoms in various organs and be anything from just tedious to life-threatening. A majority of all allergy patients are self-treated with symptom-relieving medicines, while allergen immunotherapy (AIT) is the only causative treatment option. AREAS COVERED: This review will aim to give an overview of the state-of-the-art allergy management, including the use of new biologics and the application of biomarkers, and a special emphasis and discussion on current research trends in the field of AIT. EXPERT OPINION: Conventional AIT has proven effective, but the years-long treatment compromises patient compliance. Moreover, AIT is typically not offered for food allergies. Hence, there is a need for new, effective, and safe AIT methods. Novel routes of administration (e.g. oral and intralymphatic), hypoallergenic AIT products, and more effective adjuvants hold great promise. Most recently, the development of allergen-specific monoclonal antibodies for passive immunotherapy may also allow the treatment of patients currently not treated or treatable.

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.