AllergyBLOCK · Blocking peanut allergy through protective IgG antibodies

Blocking peanut allergy through protective IgG antibodies

Food allergies are chronic and potentially fatal diseases for which there is no approved treatment other than food allergen avoidance. Such avoidance is difficult since many foods contain traces of allergens sufficient to trigger important allergic reactions. The European Commission has therefore created a Labelling Directive (2000/13/EC) obliging manufacturers to list major allergens present in pre-packaged foods sold in the EU. However, despite this directive, the prevalence of food allergies has recently increased, now affecting ~6% of people in Europe3. Among all food allergies, peanut allergy (PA) is a particularly important public health problem since PA tends to persist throughout life and is more likely than other types of food allergies to cause severe shock (i.e., “anaphylaxis”) and death. The current paradigm states that PA is mostly triggered by IgE antibodies. Evidence derived from mouse models indicates that some IgG isotypes can also mediate allergic reactions, but the roles of human IgG in PA remain unknown. Among the potential treatments for PA under investigation, oral immunotherapy (OIT) appears very promising since subjects completing OIT tolerate food challenges despite persistent high-titers of IgE in the blood. OIT consists of the administration of slowly increasing doses of the allergenic food over several months/years and is associated with the production of large levels of IgG, but a direct link between these antibodies and the beneficial effects of OIT has not been demonstrated. We hypothesize that PA patients produce both pro-allergic and protective IgG, and that successful OIT is associated with an increased production of protective IgG that are particularly potent at blocking the allergic reaction. Our main objective are to: • Determine which IgG isotypes produced by PA patients are pro-allergic. • Determine which IgG isotypes produced during peanut OIT are protective. • Demonstrate that protective IgG can be used to treat PA and/or improve OIT protocols. We propose to demonstrate this by developing and exploiting ‘humanized’ mouse models of PA, combined with the use of clinical samples and purified IgG from PA patients completing a phase 2 OIT clinical trial.

Data: CORDIS, © European Union