Current and Emerging Immunotherapeutic Approaches to Treat and Prevent Peanut Allergy

Darren S Miller; Michael P Brown; Paul M Howley; John D Hayball


Expert Rev Vaccines. 2012;11(12):1471-1481. 

In This Article

Novel Therapeutic Strategies

Mutated Peanut Protein Substitutes

Rather than avoiding peanuts, this approach enables the consumption of a 'defanged' food source. The primary amino acid sequences of IgE-binding epitopes of the major allergens present in foods are altered to reduce specific IgE binding.[76] This is possible because the specific IgE antibody binding to food allergens occurs to linear amino acid sequences in contrast to the binding of IgE antibody to inhaled allergens, which typically have conformational epitopes.[77] This technique has been shown to substantially decrease or inhibit IgE antibody binding with major peanut allergens. The major peanut allergens, Ara h 1, Ara h 2 and Ara h 3, have been mutated to make their complementary DNA, from which the mutated hypoallergenic proteins can be made. The major T-cell epitopes were not altered by mutating the IgE-binding sites. Peanut allergic patients had significantly reduced peanut-specific IgE binding to the mutated peanut protein compared with the wild-type peanut protein,[78] and it is possible that future peanut crops could be grown with the mutated sequences, resulting in a hypoallergenic food product and hence allowing consumption in otherwise allergic individuals. Nonetheless, this approach has the disadvantage of being bypassed if a peanut-allergic individual is exposed to wild-type peanut proteins and, hence, conceptually is little different to peanut avoidance.

Another approach directly confronts the question of avoidance by proposing early exposure of the immature infant immune system to peanuts. The Learning Early About Peanut (LEAP)[202] (identifier: NCT00329784) clinical trial has enrolled approximately 640 children between 4 and 10 months of age and is designed to evaluate whether or not early exposure to peanuts in children with eczema or food allergy (high risk of developing peanut allergy) can promote immunological tolerance to these proteins. Assessment of tolerance or reactogenicity will be completed at 5 years of age to determine which works best in inducing tolerance to peanut protein, avoidance or consumption? The results of this study have the potential to drive future recommendations on peanut exposure. The trial is due for completion in 2013.