Epicutaneous Immunotherapy for Aeroallergen and Food Allergy

Abstract

Opinion statementIgE-mediated allergies today affect up to 30 % of the population in industrialized countries. Allergen immunotherapy is the only disease-modifying treatment option with a long-term effect. However, very few patients (<5 %) choose immunotherapy, due to the long treatment duration (between 3–5 years) and possible local and systemic allergic side effects of the allergen administrations. The latter occur when an allergen accidentally reaches the blood circulation. Therefore, the ideal application route for allergen immunotherapy should be characterized by two hallmarks: firstly, by a high number of potent antigen-presenting cells, which enhance efficacy and thus shorten treatment duration. Secondly, the allergen administration site is ideally non-vascularized, so that inadvertent systemic distribution of the allergen and consequent systemic allergic side effects are minimized. The epidermis contains high numbers of potent antigen-presenting Langerhans cells and, as an epithelium, is non-vascularized. Therefore, the epidermis represents an interesting administration route. Historical evidence for the clinical efficacy of epicutaneous allergy immunotherapy (EPIT) has now been strengthened by a number of recent double-blinded placebo-controlled clinical trials performed by independent groups. We review the immunological rationale, history and clinical experience with epicutaneous allergy immunotherapy.

Transdermal delivery of bovine milk vesicles in patients with multiple sclerosis: A novel strategy to induce MOG-specific tolerance

“…Moreover, presence of a high number of potent antigen-presenting cells (APCs), makes epidermis an ideal application route for antigen immunotherapy. This is because these APCs enhance efficacy and thus shorten treatment duration; in addition, the antigen administration site is ideally non-vascularized, so that inadvertent systemic distribution of the allergen and consequent systemic allergic side effects are minimized [15].…”

“…More recently, a number of clinical trials have introduced epicutaneous immunotherapy as an effective approach to induce antigen-specific gastrointestinal Treg and to protect against food-induced allergies [15]. Accordingly, using bovine milk and/or its derived vesicles, epicutaneous immunotherapy may partly terminate the concern about possible adverse effects of milk consumption in patients with MS.…”

Superior Suppressive Capacity of Skin Tregs Compared with Lung Tregs in a Model of Epicutaneous Priming

“…Epicutaneous immunotherapy with allergen has been demonstrated as being a potential alternative, needle-free, and self-administrable treatment route for subcutaneous immunotherapy in both animal and human studies (reviewed in Senti et al (2014)). Our findings contribute to this therapeutic application by demonstrating that skin Tregs increase with repetitive EC antigen exposure and, furthermore, that there are functional differences between skin and lung Tregs after repetitive local antigen exposure.…”

New advances in allergy immunotherapy

“…Epicutaneous immunotherapy (EPIT) was developed in order to minimize allergen entry into the vasculature, shorten treatment duration, and provide a more convenient, needle-free, option for desensitization [69]. One method for delivering allergens to dermal Langerhans cells is by disruption of the stratum corneum with adhesive strips, which also stimulates keratinocytes, enhances Th1 cytokine production, and further activates Langerhans cells [70,71].…”

“…A five-grass pollen EPIT trial, using adhesive stripping, was stopped because of unacceptable adverse reactions [74 & ]. These safety concerns represent a major limitation in using higher doses of allergen protein with EPIT [69]. However, in a murine model for allergic asthma, EPIT using a hypoallergen (rBet v 1B2) demonstrated improved suppression of airway inflammation, compared to wild-type rBet v 1, with reduced allergic side effects [75].…”