Peanut therapeutics and diagnostics to treat severe food allergies

Up to 10% of the US population suffers from food allergies, with more than 40% of those experiencing life-threatening anaphylaxis. Peanut is one of the most common food allergens that give rise to persistent IgE-mediated food allergy. Oral immunotherapy (OIT) is used to reduce sensitivity to an allergen through repeated, small-dose exposure to the allergen. However, only a subset of patients develop a sustained response to the allergen and OIT carries notable side effects. 

Researchers were able to determine how human antibodies interact with peanut allergens. They identified three immunodominant epitopes on the major peanut allergen, Ara h 2, that led to sustained tolerance to the allergen. Select amino acid residues on Ara h 2 were mutated to abrogate binding to patient antibodies. These mutant Ara h 2 proteins could be used to determine if patients possess these key antibodies and to track patient progress towards sustained tolerance.

The same Ara h 2 mutations that knock out individual antibody binding could be combined into a so-called hypoallergen which demonstrated a reduced ability to inhibit IgE from sera binding in allergic patients. Using a mouse model for passive cutaneous anaphylaxis, the researchers saw a reduction in anaphylactic response using the Ara h 2 hypoallergen when the mouse was primed with pooled human allergic sera. This indicates that the hypoallergenic Ara h 2 mutant could be used as a safer therapy to reduce the risk of adverse events including anaphylactic responses to peanuts.  Using the diagnostics proposed above, the hypoallergen could be customized for individual patients to tailor the risk of anaphylaxis and therapeutic effectiveness.