Epicutaneous Immunotherapy Research Articles

Recent advances in food allergen immunotherapy.

Food allergies can pose significant risks and profoundly impact the quality of life of children and their families, making them a major public health concern. Allergen avoidance has been the traditional mainstay of treatment; however, recent research has focused on various approaches to food allergen immunotherapy. This review summarizes the recent advancements in oral, sublingual, and epicutaneous immunotherapies, highlighting their respective advantages and disadvantages. The ultimate goal of food allergen immunotherapy is to maximize efficacy while minimizing risks, leading to the exploration of strategies such as low-dose immunotherapy and the use of biologics. When selecting candidates for immunotherapy among patients with food allergies, factors such as allergen characteristics, the likelihood of natural resolution, age, symptom severity, and impact on quality of life require consideration, and an individualized approach should be adopted to determine the most suitable treatment method.

Immunothérapies épicutanées et sublinguales : efficacité, tolérance et place dans la prise en charge de l’allergie alimentaire

Oral immunotherapy (OIT) is the only treatment usable in practice for inducing tolerance in food-allergic patients. However, adverse events often lead to OIT refusal or discontinuation. Epicutaneous (EPIT) and sublingual (SLIT) immunotherapies are protocols developed concurrently with OIT, mainly for peanut allergy. They share immunological principles, capitalizing on Langerhans cells found in oral and cutaneous tissues to induce regulatory T lymphocytes and produce allergen-specific immunoglobulin G4 (IgG4). However, both EPIT and SLIT expose patients to smaller amounts of allergen compared to OIT. EPIT and SLIT are usually well tolerated, and have a lower risk of anaphylaxis when compared to OIT. Despite the lack of studies offering direct comparison, the ability of EPIT and SLIT to increase the tolerance threshold while on treatment seems lower compared to OIT. However, it appears that they have similar potential to OIT in terms of adjusting allergen-specific IgE and IgG4 serological responses as well as disease progression, especially in the age group of 1–4. EPIT and SLIT appear as complementary treatments to OIT, promoting medium- to long-term tolerance in peanut-allergic patients. These treatments could have an indication in patients who are ineligible, have failed, or refused OIT, or even as a first-line treatment to rescue a primary prevention failure in early childhood.

Recent advances in epicutaneous immunotherapy and potential applications in food allergy.

Given the potent immunological properties of the skin, epicutaneous immunotherapy (EPIT) emerges as a promising treatment approach for inducing immune tolerance, particularly for food allergies. Targeting the highly immunocompetent, non-vascularized epidermis allows for the application of microgram amounts of allergen while significantly reducing the risk of allergen passage into the bloodstream, thus limiting systemic allergen exposure and distribution. This makes EPIT highly suitable for the treatment of potentially life-threatening allergies such as food allergies. Multiple approaches to EPIT are currently under investigation for the treatment of food allergy, and these include the use of allergen-coated microneedles, application of allergen on the skin pretreated by tape stripping, abrasion or laser-mediated microperforation, or the application of allergen on the intact skin using an occlusive epicutaneous system. To date, the most clinically advanced approach to EPIT is the Viaskin technology platform. Viaskin is an occlusive epicutaneous system (patch) containing dried native allergen extracts, without adjuvants, which relies on frequent application for the progressive passage of small amounts of allergen to the epidermis through occlusion of the intact skin. Numerous preclinical studies of Viaskin have demonstrated that this particular approach to EPIT can induce potent and long-lasting T-regulatory cells with broad homing capabilities, which can exert their suppressive effects in multiple organs and ameliorate immune responses from different routes of allergen exposure. Clinical trials of the Viaskin patch have studied the efficacy and safety for the treatment of life-threatening allergies in younger patients, at an age when allergic diseases start to occur. Moreover, this treatment approach is designed to provide a non-invasive therapy with no restrictions on daily activities. Taken together, the preclinical and clinical data on the use of EPIT support the continued investigation of this therapeutic approach to provide improved treatment options for patients with allergic disorders in the near future.

Food allergy: Trends in the development of allergen-specific immunotherapy technologies

BACKGROUND: Food allergy is an urgent problem for public health around the world. One of the most promising methods of food allergy treatment is allergen-specific immunotherapy.
 AIM: to analyze the results of clinical studies on the effectiveness and safety of modern allergen-specific immunotherapy technologies in the treatment of food allergies published over the past three years.
 MATERIALS AND METHODS: A search and analysis of scientific publications was carried out using resources cataloging biomedical scientific literature: PubMed and eLibrary. The review includes original studies published between January 1, 2020 and December 31, 2022.
 RESULTS: The review made it possible to systematize the data accumulated over the past three years, reflecting the main trends in allergen-specific immunotherapy of food allergy. The analysis of studies showed modern approaches to oral and epicutaneous immunotherapy and affected the efficacy and safety of these types of treatment. In food allergy cohorts, the allergen-specific immunotherapy approach of oral and epicutaneous allergen-specific immunotherapy has been shown to be highly effective in achieving tolerance and desensitization to the food trigger it was revealed that epicutaneous allergen-specific immunotherapy is characterized by a high level of adherence of patients to treatment.
 CONCLUSION: It is necessary to continue conducting large-scale clinical studies on modern methods of allergen-specific immunotherapy in patients with food allergies to form standardized therapy protocols.

Preclinical evaluation of alternatives to oral immunotherapy for food allergies.

The increasing food allergy incidence has led to significant interest in developing therapies for allergic diseases. Oral allergen-specific immunotherapy (OIT) is a recently FDA-approved therapeutic to treat peanut allergies. OIT utilizes daily allergen dosing to reduce allergic reactions to peanuts. However, there is diminished enthusiasm for daily OIT, potentially due to the strict regimen required to induce desensitization and the risks of severe adverse events. Thus, there remains a need for safe and effective food allergy treatments that are well-received by allergic individuals. Preclinical research studies investigate methods to induce allergen desensitization in animals and support clinical studies that address the limitations of current food allergy OIT. Because allergic reactions are triggered by allergen doses above an individual's activation threshold, immunotherapy regimens that induce allergen desensitization with lower allergen doses or without the requirement of daily administrations may expand the use of food allergy immunotherapy. Administering allergen immunotherapy by alternative routes is a strategy to induce desensitization using lower allergen doses than OIT. Several animal models have evaluated oral, sublingual, epicutaneous, and intranasal immunotherapy routes to treat food allergies. Each immunotherapy route may require different allergen doses, formulations, and treatment schedules to induce desensitization. This article will discuss scientific findings from food allergy immunotherapy animal studies that utilize various immunotherapy routes to induce allergen desensitization to support future clinical studies that enhance the safety and efficacy of allergen immunotherapy to treat food allergies.

Epicutaneous Immunotherapy for Peanut Allergy: A Promising Treatment for Young Children

Epicutaneous Immunotherapy for Peanut Allergy: A Promising Treatment for Young Children

Modulation of immune response by nanoparticle-based immunotherapy against food allergens.

The increasing prevalence of food allergies worldwide and the subsequent life-threatening anaphylactic reactions often have sparse treatment options, providing only symptomatic relief. Great strides have been made in research and in clinics in recent years to offer novel therapies for the treatment of allergic disorders. However, current allergen immunotherapy has its own shortcomings in terms of long-term efficacy and safety, due to the local side effects and the possibility of anaphylaxis. Allergen-specific immunotherapy is an established therapy in treating allergic asthma, allergic rhinitis, and allergic conjunctivitis. It acts through the downregulation of T cell, and IgE-mediated reactions, as well as desensitization, a process of food tolerance without any allergic events. This would result in a protective reaction that lasts for approximately 3 years, even after the withdrawal of therapy. Furthermore, allergen-specific immunotherapy also exploits several routes such as oral, sublingual, and epicutaneous immunotherapy. As the safety and efficacy of allergen immunotherapy are still under research, the exploration of newer routes such as intra-lymphatic immunotherapy would address unfulfilled needs. In addition, the existence of nanoparticles can be exploited immensely in allergen immunotherapy, which would lead to safer and efficacious therapy. This manuscript highlights a novel drug delivery method for allergen-specific immunotherapy that involves the administration of specific allergens to the patients in gradual increasing doses, to induce desensitization and tolerance, as well as emphasizing different routes of administration, mechanism, and the application of nanoparticles in allergen-specific immunotherapy.

New insights in the optimal diagnosis and management of food allergy.

Background: In recent years, food allergy has become a rising global epidemic, more so in Western countries. Although genetics may play a role in this increase, there are many other factors that have contributed to the upsurge. Recent research has shown that introducing allergenic foods to infants at an early age can reduce the risk of developing allergies to those foods. This is a substantial departure from traditional advice, which had recommended delaying the introduction of potential allergenic foods until a child was at least 1 year old and, in some cases, until the child was much older. Objective: The purpose of the present report is to review the epidemiology, mechanisms, and new prevention strategies for food allergies, and to discuss new treatment modalities associated with immune tolerance, which include the use of biologics as well as new forms of allergen immunotherapy (AIT) such as oral immunotherapy (OIT), sublingual immunotherapy (SLIT), and epicutaneous immunotherapy (EPIT), which have particular relevance for the allergist/immunologist. Results: Innovative developments in the treatment of food allergies have emerged through improved comprehension of immune tolerance and the induction of regulatory T (Treg) cells, the understanding of T-helper type 2 (Th2) cell-driven responses and their associated proinflammatory cytokine production, epitope mapping techniques, and the utilization of drugs such as monoclonal antibodies that target interleukin (IL) 4, IL-5, and IL-13 to disrupt Th2 cell-related pathways. In addition, there have been significant advancements in new forms AIT methods, which include OIT, SLIT, and EPIT. Conclusion: The present report reviews several of the many aspects of food allergy that have been impacted by this new knowledge and which have led to new insights for the optimal diagnosis and management of food allergy, and has had important implications for the diagnosis, treatment, prevention, and management of these conditions. The improved understanding of Treg-related mechanisms of immune tolerance and Th2 cell-driven responses associated with the production of proinflammatory cytokines associated with these responses, together with epitope mapping techniques, have played a crucial role in enhancing the diagnosis and management of food allergies. By identifying these variables, the allergist/immunologist is better equipped to tailor new diagnostic approaches and develop targeted therapies to significantly impact the lives of individuals affected by food allergies.

Innovative delivery systems for epicutaneous immunotherapy.

Allergen-specific immunotherapy (AIT) describes the establishment of peripheral tolerance through repeated allergen exposure, which qualifies as the only curative treatment for allergic diseases. Although conventional subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) have been approved to treat respiratory allergies clinically, the progress made is far from satisfactory. Epicutaneous immunotherapy (EPIT) exploits the skin's immune properties to modulate immunological response, which is emerging as a promising alternative and has shown effectiveness in many preclinical and clinical studies for both respiratory and food allergies. It is worth noting that the stratum corneum (SC) barrier impedes the effective delivery of allergens, while disrupting the SC layer excessively often triggers unexpected Th2 immune responses. This work aims to comprehend the immunological mechanisms of EPIT, and summarize the innovative system for sufficient delivery of allergens as well as tolerogenic adjuvants. Finally, the safety, acceptability, and cost-effectiveness of these innovative delivery systems are discussed, which directs the development of future immunotherapies with all desirable characteristics.

Epicutaneous Immunotherapy for Peanut Allergy

Epicutaneous Immunotherapy for Peanut Allergy

Update on oral and epicutaneous immunotherapy for children with food allergy

Update on oral and epicutaneous immunotherapy for children with food allergy

The Efficacy and Safety of Epicutaneous Immunotherapy for Milk Allergy: A Systematic Review

Introduction: Cow’s milk allergy (CMA) is rising among children and adults, affecting 2-3% of children in affluent countries. Currently, the only standard of care is dairy restriction. However, epicutaneous immunotherapy (EPIT) is being studied as a potential treatment involving transdermal administration of an allergen to induce tolerance. EPIT has been proven safe for managing other food allergies in children and adolescents, but its efficacy for CMA is yet to be determined. Methods: A systematic search of four databases (PubMed, ScienceDirect, SCOPUS, and clinicaltrials.gov) was conducted in September 2022 by three independent reviewers. Additional studies were found by manual reference browsing. All published articles and randomized controlled trials (RCTs) that assessed the effect of EPIT on CMA in children and adolescents aged ≤18 years were included. The search terms used were “epicutaneous immunotherapy” or “immunotherapy” or “EPIT”; “milk allergy” or “cow’s milk allergy” or “CMA” or “CMPA”; “children” or “young” or “kids.” Results: Six studies were included after a systematic search of 123 studies, with three RCTs evaluating the safety and efficacy of EPIT in children with CMA and three meta-analyses and reviews on EPIT for CMA. The findings were inconclusive but suggested the possibility of treating cow’s milk allergy. Discussion: EPIT shows promise in treating food allergies, including CMA. Evidence is lacking to determine its efficacy for CMA. More clinical trials with different dosages and longer follow-ups are needed. Results should be interpreted with caution due to limited studies.

Updates in food allergen immunotherapy.

Food allergies are on the rise. Though allergen avoidance and management of acute reactions have been the backbone of therapy, complete avoidance and timely acute care is often not feasible. Food allergen immunotherapy (FAIT) is a novel and evolving treatment option intended to induce desensitization and potential sustained unresponsiveness (SU) to food allergens. This review addresses the methods, mechanisms, efficacy, and adverse effects of oral immunotherapy (OIT), sublingual immunotherapy (SLIT), and epicutaneous immunotherapy (EPIT) for food allergens in the published literature. Single FAIT has been most extensively studied in peanut, milk, and hen's egg allergic patients and has been successful in achieving desensitization in treated individuals through various modalities. Long-term data regarding SU is limited; however, current data suggests subsets of patients may be more likely to achieve SU compared to others. Other studies are actively assessing multifood AIT and novel FAIT protocols with adjunctive therapies. Food allergy constitutes a prevalent problem with far-reaching consequences. The emergence of FAIT may mitigate the burden of food allergy. Current evidence is promising for specific allergens and pediatric patient populations. Future studies are needed to further assess efficacy between different modalities of immunotherapy for food allergens across an age continuum.

Mechanisms of desensitization with oral immunotherapy and epicutaneous immunotherapy.

Oral immunotherapy (OIT) and epicutaneous immunotherapy (EPIT) are emerging therapies for food allergy. With several recently published exploratory trials and randomized controlled clinical trials that support these procedures, there is a clear progress and interest toward making these treatment options available for allergist/immunologists and patients with food allergies entrusted to their care. However, there still remain many questions and concerns to be addressed before these procedures can be fully understood. The purpose of the present report is to trace some of the important historical milestones in the development of OIT and EPIT that have contributed to their evolving clinical application to the treatment of food allergy, to describe some of the current understandings of the immunologic mechanisms by which these procedures elicit desensitization, and to provide some areas for future inquiry and research. An extensive research was conducted in the medical literature data bases by applying terms such as food allergy, desensitization, tolerance, unresponsiveness, Treg cells, allergen immunotherapy (AIT), oral immunotherapy (OIT), and epicutaneous immunotherapy (EPIT). OIT and EPIT take their origins from AIT (also called desensitization), a procedure first reported for the treatment of hay fever over a 100 years ago in which slowly increasing doses of a specifically relevant allergen were administered until a maintenance dosage was achieved when the patient was free of symptoms. OIT and EPIT differ from AIT in certain aspects including the route of administration of the allergen as well as their relative shorter period of sustained unresponsiveness. The origins and important historical landmarks that have been made in the field of food allergy immunotherapy are presented in the context of the immunologic mechanisms that contribute to the pathogenesis of these disorders. Although considerable progress has been made in recent years toward making these treatment options available for allergist/immunologists and patients with food allergies, there still remain many questions and concerns to be addressed before these procedures can be fully understood, which can be illuminated by future research.

Phase 3 Trial of Epicutaneous Immunotherapy in Toddlers with Peanut Allergy

BackgroundNo approved treatment for peanut allergy exists for children younger than 4 years of age, and the efficacy and safety of epicutaneous immunotherapy with a peanut patch in toddlers with peanut allergy are unknown.MethodsWe conducted this phase 3, multicenter, double-blind, randomized, placebo-controlled trial involving children 1 to 3 years of age with peanut allergy confirmed by a double-blind, placebo-controlled food challenge. Patients who had an eliciting dose (the dose necessary to elicit an allergic reaction) of 300 mg or less of peanut protein were assigned in a 2:1 ratio to receive epicutaneous immunotherapy delivered by means of a peanut patch (intervention group) or to receive placebo administered daily for 12 months. The primary end point was a treatment response as measured by the eliciting dose of peanut protein at 12 months. Safety was assessed according to the occurrence of adverse events during the use of the peanut patch or placebo.ResultsOf the 362 patients who underwent randomization, 84.8% completed the trial. The primary efficacy end point result was observed in 67.0% of children in the intervention group as compared with 33.5% of those in the placebo group (risk difference, 33.4 percentage points; 95% confidence interval, 22.4 to 44.5; P<0.001). Adverse events that occurred during the use of the intervention or placebo, irrespective of relatedness, were observed in 100% of the patients in the intervention group and 99.2% in the placebo group. Serious adverse events occurred in 8.6% of the patients in the intervention group and 2.5% of those in the placebo group; anaphylaxis occurred in 7.8% and 3.4%, respectively. Serious treatment-related adverse events occurred in 0.4% of patients in the intervention group and none in the placebo group. Treatment-related anaphylaxis occurred in 1.6% in the intervention group and none in the placebo group.ConclusionsIn this trial involving children 1 to 3 years of age with peanut allergy, epicutaneous immunotherapy for 12 months was superior to placebo in desensitizing children to peanuts and increasing the peanut dose that triggered allergic symptoms. (Funded by DBV Technologies; EPITOPE ClinicalTrials.gov number, NCT03211247.)

Immune response evolution in peanut epicutaneous immunotherapy for peanut-allergic children.

Epicutaneous immunotherapy with investigational Viaskin™ Peanut 250 μg (DBV712) has demonstrated statistically superior desensitization versus placebo in peanut-allergic children in clinical trials. It is unclear whether serologic biomarkers predict response. Serum-specific IgG4 and IgE (whole peanut and components) from subjects enrolled in the phase 3 Efficacy and Safety of Viaskin Peanut in Children With IgE-Mediated Peanut Allergy study were examined by exploratory univariate and multivariate analyses to determine trajectories and predictors of treatment response, based upon peanut protein eliciting dose (ED) at Month (M) 12 double-blind placebo-controlled food challenge. Among Viaskin Peanut-treated subjects, peanut sIgG4 significantly increased from baseline through M12 and peanut sIgE peaked at M3 and fell below baseline by M12, with sIgG4 and sIgE peanut components mirroring these trajectories. Placebo subjects had no significant changes. By univariate analysis, M12 peanut sIgG4/sIgE was higher in treatment responders (p< 0.001) and had highest area under the curve (AUC) for predicting ED ≥300 mg and ≥1000 mg (AUC 69.5% and 69.9%, respectively). M12 peanut sIgG4/sIgE >20.1 predicted M12 ED ≥300 mg (80% positive predictive value). The best performing component was Ara h 1 sIgE <15.7 kUA /L (AUC 66.5%). A multivariate model combining Ara h 1 and peanut sIgG4/sIgE had an AUC of 68.2% (ED ≥300 mg) and 67.8% (ED ≥1000 mg). Peanut sIgG4 rise most clearly differentiated Viaskin Peanut versus placebo subjects. sIgG4/sIgE ratios >20.1 and the combination of Ara h 1 and peanut sIgG4/sIgE had moderate ability to predict treatment response and could potentially be useful for clinical monitoring. Additional data are needed to confirm these relationships.

Sustained antigens delivery using composite microneedles for effective epicutaneous immunotherapy.

Allergen-specific immunotherapy (SIT) is a desirable way of therapy for various allergic diseases such as food allergy (FA). However, frequent visits for more than 3 years and potential adverse effects often hinder patient compliance. Recently, many researchers started focusing on microneedles (MNs) as a new method for SIT. In this study, we proposed an implantable MNs system produced by a two-step casting process, consisting of OVA (antigen)-loaded silk microneedles and a dissolvable, flexible polyvinyl alcohol (PVA) pedestal. Different from PVA, silk fibroin hydrogel has preferable vaccine release ability in vivo and in vitro. Once MNs are inserted into the skin, the PVA pedestal can dissolve in the interstitial fluid of the excised skin within 5 min and implant the OVA-loaded silk microneedle tips in dermal layer as a sustained antigen depot, thus inducing long-lasting immune response for at least 2 weeks. After receiving 3 doses of MN-based immunotherapy, the immune response in OVA-sensitized mice was successfully suppressed, with no apparent side effects. Compared to conventional subcutaneous immunotherapy (total dose of 150 [Formula: see text]g), MN immunotherapy ameliorated systemic anaphylaxis more effectively even at a lower dose (total dose of 30 [Formula: see text]g), demonstrating the antigen dose-sparing potential of the proposed MNs. Moreover, due to the prolonged release effect of silk-PVA composite MNs, the frequency of immunotherapy can be significantly reduced. To sum up, through prolonged skin exposure to antigen, this implantable designed MN may offer a new therapeutic strategy for FA treatment with significant improvements in efficacy and convenience. Schematic illustration of silk-PVA composite microneedles, consisting of OVA (antigen)-loaded silk microneedles and a dissolvable, flexible PVA pedestal. Once inserted into the skin, the PVA pedestal can dissolve in the interstitial fluid of the excised skin within 5 min. Subsequently, the OVA-loaded silk microneedle tips were implanted in the dermal layer as a sustained antigen depot and induced long-lasting immune response. This MNs-based immunotherapy can significantly modulate the Th1/Th2 imbalance of sensitized mice.

Transgenerational development of food allergies and allergic rhinitis

Both environmental and genetic factors play a role in allergies. Allergies are influenced by genes and how they control immune cell function. Several studies have examined the occurrence of allergic disease in children and its association with other risk factors, including allergic disease in parents. Specific toxins like CO2 and other health conditions can be related to the diagnosis of allergic rhinitis. The response to food allergies was observed in many studies to conclude that heritability from parents to offspring is one of the leading risk factors for allergic diseases. Several studies have found a significant increase in the prevalence of allergic rhinitis in males than in females. Avoidance of a particular food was associated with an increased risk of developing an allergy to that food. At the molecular level, T cells are found to affect allergy outcomes through their part of the immune response. Food proteins such as milk, egg, and peanut - common food allergens - may cause an immune response in allergic individuals. Different therapies include Epicutaneous Immunotherapy (EPIT) and specific infant milk protein formulas. If this formula is taken from infancy, the allergic responses can be prevented/reduced. As with seasonal allergies, prevention can be mediated by avoiding different pollution environments that may cause additional irritation, temperature control in a given atmosphere/humidity, and therapies of Vitamin C for immunity. With many other seasonal allergy triggers, it is ubiquitous among populations and dependent on the area and season.

Efficacy and Safety of Epicutaneous Immunotherapy (EPIT) for Peanut Allergy in Subjects Aged 1-3 Years With and Without Atopic Dermatitis in the EPITOPE Study

In a Phase 3 double-blind, placebo-controlled clinical trial of 1-3-year-old peanut-allergic children (EPITOPE), EPIT with Viaskin Peanut 250 μg patch (VP250) reduced reactivity to peanut ingestion. We explored whether treatment response or safety was influenced by baseline atopic dermatitis (AD) in this population.

Efficacy and safety of peanut epicutaneous immunotherapy in patients with atopic comorbidities.

Co-occurring atopic conditions are common in children with peanut allergy. As such, it is important to examine the safety and efficacy of epicutaneous immunotherapy with Viaskin Peanut 250 μg patch (VP250) in peanut-allergic children with these conditions. We sought to compare efficacy and safety of VP250 versus placebo in peanut-allergic children with/withoutongoing atopic conditions at baseline, includingasthma, atopic dermatitis/eczema, or concomitant food allergy. A subgroup analysis of peanut-allergic children aged 4 to 11 years enrolled in PEPITES (12 months) and REALISE (6 months) randomized, placebo-controlled, phase 3 trials was conducted. The efficacy outcome measure was the difference in prespecified responder rate between placebo and VP250 groups at month 12 based on eliciting dose of peanut protein using double-blind, placebo-controlled food challenge in PEPITES. Safety profiles were evaluated by baseline concomitant disease subgroup in all randomized subjects who received 1 or more dose of the study drug in PEPITES and REALISE pooled data. Responder rates were significantly (P< .05, all comparisons) greater with VP250 compared with placebo treatment regardless of whether subjects had other atopic conditions. Safety and tolerability profiles were generally similar across subgroups, with no new safety concerns detected. Atrend for both higher responder rates and rates of local reactions was observed in subjects with baseline atopic dermatitis versus those without. In subjects with concomitant food allergy at baseline, higher rates of treatment-emergent adverse events, but not study discontinuations or overall rates of anaphylaxis, were observed. The results support the safety and efficacy of VP250 for treating peanut-allergic children with or without concomitant atopic conditions.