Specific Immunotherapy for Food Allergy with Mutated Proteins

Currently the only treatment for food allergy is strict avoidance of the offending food. In the past years much effort has been made to develop new treatment methods. Specific immunotherapy using injections is commonly used for the treatment of inhalant allergies. However, for food allergy it is

IgE-binding epitope Single amino acid substitution results in loss of IgE binding

IgE-binding epitope Single amino acid substitution results in loss of IgE binding

Fig. 3. IgE-binding sites have been identified for many food allergens. Mutation through single amino acid substitution at these binding sites resulted in reduced to complete loss of IgE-binding.

currently not recommended because of the allergic side effects of the therapy. A study by Oppenheimer et al. [17] showed that patients with peanut allergy tolerated an increased amount of peanuts following a rush immuno-therapy but an unacceptable rate of adverse systemic reactions occurred.

As traditional immunotherapy has been largely impractical for the treatment of food allergies, several novel therapies are currently being explored [18, 19]. One of the most promising approaches is the immunotherapy with mutated proteins. Within the last couple of years food allergens have been better characterized [2, 20]. IgE-binding sites have been identified for many of these food allergens [21-26]. With this knowledge attempts to alter IgE antibody binding through alteration of the amino acid sequences of the IgE-binding sites have started (fig. 3). Mutation through single amino acid substitution resulted in reduced to complete loss of IgE binding [26-29]. For the major peanut allergens Ara h 1, Ara h 2 and Ara h 3 such mutations were introduced into the cDNA sequences and successfully expressed as hypoal-lergenic recombinant proteins [18]. Most importantly, mutation of the IgE-binding sites appears to leave the T cell response unaffected [30].

In peanut-sensitized mice, the use of these modified proteins showed some protection; however, alone it did not appear to be adequate for the treatment of peanut allergy [19]. However, using co-administration of modified peanut proteins and heat-killed Listeria monocytogenes as an adjuvant resulted in much better protection [19]. However, although modified proteins reduce the concern regarding activation of mast cells during immunotherapy, the safety of subcutaneous injections of heat-killed L. monocytogenes remains to be determined. Another promising approach appears to be the rectal administration of mutated proteins with heat-killed Escherichia coli as an adjuvant. This novel immunotherapeutic approach has the benefit that expensive purification of the engineered proteins generated in E. coli is not necessary because it is administered into an environment replete withE. coli [19].

Although animal studies using mutated hypoallergenic proteins seem to be very promising, studies in humans will be necessary to prove the effect.

Heterogenicity in IgE-binding sites and amino acids critical for IgE binding as shown for cow's milk proteins [29] might lead to problems that need to be addressed in the future.

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