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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. [ABSTRACT FROM AUTHOR]

Background: Peanut allergy accounts for the majority of food‐induced hypersensitivity reactions and can lead to lethal anaphylaxis. Animal models can provide an insight into the immune mechanisms responsible for sensitization and allergic anaphylaxis. However, different mouse strains and sensitization protocols can influence the successful development of a peanut allergic mouse model. Objective: We aimed at developing a systemic anaphylaxis model of peanut allergy that resembles human anaphylaxis. We compared the immunological and clinical responses in genetically different mouse strains. Methods: Female BALB/c, C57BL/6, and C3H mice were intraperitoneally sensitized and later challenged with peanut proteins. Allergen‐specific serology was done by ELISA, and anaphylaxis was evaluated by monitoring changes in body temperature upon systemic challenge. Results: Sensitization to peanut was successful in C3H mice and triggered production of allergen‐specific antibodies, cytokines and anaphylaxis. Allergic reactions were characterized by the release of allergic mediators and by changes in leukocyte populations in blood and in the peritoneal cavity. Among the identified major peanut allergens, Ara h 2 showed the strongest anaphylactic potential. Much lower or no trigger of peanut‐specific antibodies was observed in BALB/c and C57BL/6 mice, which experienced no hypersensitivity reactions. Conclusions: Mouse strain matters for testing of peanut protein allergens. We identified C3H mice as a suitable strain for the development of a mouse model of peanut‐allergic anaphylaxis. Pre‐clinical, humoural and cellular responses resembled the responses observed in human patients. The described model can be useful for further studies on peanut allergy and for the development of new therapeutic strategies. [ABSTRACT FROM AUTHOR]

The most common pattern of poly-sensitization included the allergens Ara h 1, Ara h 2, Ara h 3 and Ara h 6 and observed in 17 patients. IgE towards Ara h 8 and Ara h 9 did not correlate with IgE specific to Ara h 1, Ara h 2, Ara h 3 and Ara h 6 ( I r i < .1), and only slightly between each other ( I r i = .43; Figure 1G). The median anti-PE IgE ImmunoCAP concentration was 13.5 kUA/L. Lower ( I p i < .0001) median IgE levels were measured for Ara h 2 (5.6), Ara h 6 (3.7), Ara h 1 (1.2), Ara h 3 (0.13), Ara h 8 (0.85) and Ara h 9 (<0.1). Ara h 2 and Ara h 6 are the most widespread sensitizing allergens. [Extracted from the article]