Current and Emerging Immunotherapeutic Approaches to Treat and Prevent Peanut Allergy

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

Disclosures

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

In This Article

Expert Commentary

Peanut allergy is a frightening condition increasing in prevalence in which acute, life-threatening attacks can occur unpredictably. Even the sensible although burdensome strategy of allergen avoidance is not without risk since peanut contamination of modern processed foods is ominously common. Given the unpredictable nature of the attacks, any worthwhile immunotherapeutic approach must attenuate allergic reactions to trivial levels or eliminate the risk of serious reactions with certainty.

Principally, allergies are conditions of the immune system associated with a dysregulation of the TH1 and TH2 lymphocyte populations.[97–99] It has been proposed that vaccination and use of antibiotics, and increased sanitary living conditions, has resulted in a subsequent decline in occurrence of infectious diseases. Cocommittedly, TH1 immune stimulation has also declined, with a resultant increase and in some cases detrimental shift toward a TH2 bias of immune responses against normally innocuous environmental allergens, (i.e., hygiene hypothesis).[100,101] An allergen vaccine that can activate a TH1-directed immune response against the disease causing allergen offers a new approach for specific immunotherapy by redirecting the allergic TH2 immune response.

The successes and tolerability in numerous past and ongoing clinical trials of oral immunotherapy places this treatment regimen as the lead candidate for the treatment of peanut allergy. The recent discovery and full characterization of several new peanut allergens in combination with modern molecular and immunological tools has allowed for the synthesis of recombinant peanut proteins and peptides to be used in immunotherapeutic dosing protocols. For instance, the recent mapping of the Ara h 2 immunodominant epitopes and subsequent design of the HLA diverse and variant peptides that do not bind patient serum IgE but are able to bind to pathogenic CD4+ T cells, is a major advance in the field of peanut allergy. It is expected that similar testing will be performed in the near future for all the peanut allergens. In combination, these peptides may provide a simple but safe immune-modulating vaccine for peanut allergic individuals. The clinical trial named LEAP is a potentially ground-breaking study that has the potential to drive future recommendations regarding peanut consumption in children. The remarkable preclinical efficacy of FAHF-2 is suggestive of real potential but the active constituents need to be identified to ensure optimal formulation. Clearly though, the inclusion of several different immunotherapeutic modalities in combination may provide additional therapeutic benefits.

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