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Since the early nineties several approaches have been tested to develop safe and effective allergen immunotherapy (AIT) for the treatment of peanut allergy, starting with subcutaneous AIT with aqueous extract, followed by hypo-allergenic major allergens produced in bacteria that were administered rectally. These approaches were abandoned, mainly because of too many severe side-effects. Other administration routes that are considered to be safer, like sublingual and epicutaneous, have not yet reached the market. The only treatment that did receive market authorization is oral immunotherapy (OIT). It is effective for desensitization, disappointing for sustained efficacy, and side-effects occur frequently.1 Furthermore, the most sensitive patients being at risk of severe life-threatening allergic reactions are unlikely to be helped with this approach, as side-effects may include severe anaphylaxis.2 Therefore, there is an urgent need to provide all patients, including the severest ones, with a safe and effective treatment. Recently, nano- and micro-particulate strategies, such as virus-like particles, have been proposed as potentially safe and effective approaches. For example, a virus-based particle expressing the peanut allergens Ara h 1 or 2, based on the Cucumber Mosaic Virus, was shown to be hypo-allergenic in a mouse model.3 Here we report the ground-breaking hypo-allergenicity of a novel non-virus-based microparticle produced in plants, that is, enveloped bioparticles (eBPs) expressing ~3000 copies of Ara h 2 on the surface of each particle.
