Targeting Ara h 2 with human-derived monoclonal antibodies prevents peanut-induced anaphylaxis in mice.
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| Abstract | 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.
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| Authors | Marta Paolucci, Natascha Wuillemin, Valentine Homère, Dimitri Bieli, Alice Köhli, Barbara Ballmer-Weber, Ying Waeckerle-Men, Niccolò Pengo, Thomas M Kündig, Tiziana Sonati, Pål Johansen |
| Journal | Allergy (Allergy) Vol. 78 Issue 6 Pg. 1605-1614 (06 2023) ISSN: 1398-9995 [Electronic] Denmark |
| PMID | 36704937 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | © 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd. |
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