Treatment Of Peanut Allergy Research Articles

Fungal Proteases in the Preventative Treatment of Peanut Allergies: A Research Protocol

Fungal Proteases in the Preventative Treatment of Peanut Allergies: A Research Protocol

Epicutaneous immunotherapy for the treatment of peanut allergy.

Peanut allergy treatment options remain limited, but novel approaches are being studied, including epicutaneous immunotherapy (EPIT). EPIT uses the cutaneous immune system to promote tolerance to food allergens. Viaskin™ Peanut, an approach to EPIT in late-stage clinical development uses an occlusive patch with a condensation chamber that enables natural epidermal water loss to solubilize dry antigen on the patch, which is then absorbed and captured by skin Langerhans cells. This form of EPIT does not require disruption of the skin barrier, thus avoiding a proinflammatory cytokine response by targeting the nonvascularized epidermis and limiting systemic allergen exposure. Extensive preclinical research suggests that Viaskin Peanut has a distinct mechanism of desensitization, including the potential for disease modification, driven by a unique population of regulatory T cells. Numerous clinical studies of Viaskin Peanut have demonstrated desensitization and reductions in reaction severity, particularly in children aged 1 through 11 years, as well as a favorable safety profile with mostly mild-to-moderate skin reactions that were observed to decrease over time. EPIT with Viaskin Peanut may be a potential therapeutic option for peanut allergy that is clinically practical with long-term efficacy and tolerability.

Peanut Allergy in Children-Is Prevention Better than Cure?

Peanut allergy, one of the most frequently occurring allergies, usually starts in childhood and rarely subsides-often persisting throughout adult life. Accidental exposure to peanuts can often result in adverse reactions ranging from mild to life-threatening, such as anaphylactic shock. Historically, food avoidance and the use of rescue drugs have remained a fundamental management mechanism for dealing with food allergy. However, prevention of adverse reactions to food allergy is playing an increasing role. This is possible through the early introduction of peanuts into the diet, especially in infants at risk of this allergy. In recent years, specific immunotherapy has been used to develop desensitisation and, in some patients, tolerance-defined as a persistent state of clinical non-reactivity to the allergen after therapy is finished. The aim of this article is to summarise the current state of knowledge on the prevention and treatment of peanut allergy, with a focus on clinical trials, current guidelines, and recent experimental studies. This review may be particularly useful for paediatricians and general practitioners.

In Silico Identification of Peanut Peptides Suitable for Allergy Immunotherapy in HLA-DRB1*03:01-Restricted Patients.

Peanut allergy, a prevalent and potentially severe condition affecting millions worldwide, has been linked to specific human leukocyte antigens (HLAs), suggesting increased susceptibility. Employing an immunoinformatic strategy, we developed a "logo model" based on amino acid frequencies in the peptide binding core and used it to predict peptides originating from 28 known peanut allergens binding to HLA-DRB1*03:01, one of the susceptibility alleles. These peptides hold promise for immunotherapy in HLA-DRB1*03:01 carriers, offering reduced allergenicity compared to whole proteins. By targeting essential epitopes, immunotherapy can modulate immune responses with minimal risk of severe reactions. This precise approach could induce immune tolerance with fewer adverse effects, presenting a safer and more effective treatment for peanut allergy and other allergic conditions.

Evaluation and Modification of a Shared Decision-Making Tool for Peanut Allergy Management.

Based on shared decision-making (SDM) principles, a decision aid was previously developed to help patients, their caregivers, and physicians decide which peanut allergy management approach best suits them. This study refined the decision aid's content to better reflect patients' and caregivers' lived experience. Current standard of care for peanut allergy is avoidance, although peanut oral immunotherapy has been approved by the Food and Drug Administration for use in patients 4-17 years old. An advisory board of allergy therapy experts (n = 3) and patient advocates (n = 3) informed modifications to the decision aid. The revised tool underwent cognitive debriefing interviews (CDIs) among adolescents (12-17 years old) with peanut allergy and caregivers of patients 4-17 years old with peanut allergy to evaluate its relevance, understandability, and usefulness. The 20 CDI participants understood the information presented in the SDM tool and reported it was important and relevant. Some revisions were made based on participant feedback. Results support content validity of the Peanut Allergy Treatment SDM Tool.

Exploring novel approaches to food allergy management.

Nurse practitioners are likely to encounter pediatric and adult patients with symptoms of food allergy who need an accurate diagnosis, emergency treatment plans, and options for management. The pathophysiology of immunoglobulin E (IgE)-mediated food allergy, current and emerging diagnostics, treatment, and emergency management is briefly reviewed, and promising new and potential future treatment options are discussed. Currently, Food and Drug Administration-approved oral immunotherapy (OIT) treatment for peanut allergy, but clinical trials are underway to explore multiple-allergen OIT and alternate routes for IT such as sublingual and epicutaneous. Treatments that modulate the immune system are also potential treatments for food allergies (FAs), including biologic agents. Omalizumab, an anti-IgE therapy, dupilumab, an interleukin-4Ra receptor monoclonal antibody, and etokimab, an anti-IL-33, are all being studied for the treatment of food allergy. There is hope that these novel therapies for FAs will be a viable option translated to the practice setting in the near future, so that strict avoidance is not the only treatment plan for FAs. Nurse practitioners can support their patients with FAs and their families by keeping abreast of progress in food allergy research and assisting patients to consider novel treatment options, when appropriate, using shared decision making.

Influence of antigen density and TLR ligands on preclinical efficacy of a VLP-based vaccine against peanut allergy.

Virus-like particle (VLP) Peanut is a novel immunotherapeutic vaccine candidate for the treatment of peanut allergy. The active pharmaceutical ingredient represents cucumber mosaic VLPs (CuMVTT -VLPs) that are genetically fused with one of the major peanut allergens, Ara h 2 (CuMVTT -Ara h 2). We previously demonstrated the immunogenicity and the protective capacity of VLP Peanut-based immunization in a murine model for peanut allergy. Moreover, a Phase I clinical trial has been initiated using VLP Peanut material manufactured following a GMP-compliant manufacturing process. Key product characterization studies were undertaken here to understand the role and contribution of critical quality attributes that translate as predictive markers of immunogenicity and protective efficacy for clinical vaccine development. The role of prokaryotic RNA encapsulated within VLP Peanut on vaccine immunogenicity was assessed by producing a VLP Peanut batch with a reduced RNA content (VLP Peanut low RNA). Immunogenicity and peanut allergen challenge studies were conducted with VLP Peanut low RNA, as well as with VLP Peanut in WT and TLR 7 KO mice. Furthermore, mass spectrometry and SDS-PAGE based methods were used to determine Ara h 2 antigen density on the surface of VLP Peanut particles. This methodology was subsequently applied to investigate the relationship between Ara h 2 antigen density and immunogenicity of VLP Peanut. A TLR 7 dependent formation of Ara h 2 specific high-avidity IgG antibodies, as well as a TLR 7 dependent change in the dominant IgG subclass, was observed following VLP Peanut vaccination, while total allergen-specific IgG remained relatively unaffected. Consistently, a missing TLR 7 signal caused only a weak decrease in allergen tolerability after vaccination. In contrast, a reduced RNA content for VLP Peanut resulted in diminished total Ara h 2 specific IgG responses, followed by a significant impairment in peanut allergen tolerability. The discrepant effect on allergen tolerance caused by an absent TLR 7 signal versus a reduced RNA content is explained by the observation that VLP Peanut-derived RNA not only stimulates TLR 7 but also TLR 3. Additionally, a strong correlation was observed between the number of Ara h 2 antigens displayed on the surface of VLP Peanut particles and the vaccine's immunogenicity and protective capacity. Our findings demonstrate that prokaryotic RNA encapsulated within VLP Peanut, including antigen density of Ara h 2 on viral particles, are key contributors to the immunogenicity and protective capacity of the vaccine. Thus, antigenicity and RNA content are two critical quality attributes that need to be determined at the stage of manufacturing, providing robust information regarding the immunogenicity and protective capacity of VLP Peanut in the mouse which has translational relevance to the human setting.

Food Oral Immunotherapy: A Survey Among US Practicing Allergists Conducted as a AAAAI Leadership Institute Project and Work Group Report.

Food oral immunotherapy (OIT) is an active form of treatment for food allergies. Although research in this area has been ongoing for many years, the first US Food and Drug Administration-approved product for peanut allergy treatment became available only in January 2020. Limited data exist on OIT services offered by physicians in the United States. This workgroup report was developed to evaluate OIT practices among allergists practicing in the United States. The authors developed an anonymous 15-question survey and was subsequently reviewed and approved by the American Academy of Allergy, Asthma & Immunology Practices, Diagnostics and Therapeutics Committee before distribution to the membership. The American Academy of Allergy, Asthma & Immunology electronically distributed the survey to a random sample of 780 members in November 2021. In addition to questions specific to food OIT, the survey included questions on demographics and professional characteristics of the responders. A total of 78 members completed the survey, yielding a 10% response rate. Fifty percent of responders were offering OIT in their practice. There was a significant difference in experience in OIT originating from research trials in academic versus nonacademic centers. Generally, OIT practices were similar in both settings for the number of foods offered, the performance of oral food challenges before initiating treatment, the number of new patients to whom OIT was offered to per month, and age groups OIT to whom was offered. Almost all of the reported barriers to OIT were similar between settings: staff and time limitations, concerns about safety and anaphylaxis, the need for more education on how to perform, inadequate compensation, and that it was not a significant demand from patients. Clinic space limitations were significantly different and more prominent in academic settings. Our survey revealed interesting trends in the practice of OIT across the United States, with some significant differences arising when academic and nonacademic settings were compared.

An update on recent developments and highlights in food allergy.

While both the incidence and general awareness of food allergies is increasing, the variety and clinical availability of therapeutics remain limited. Therefore, investigations into the potential factors contributing to the development of food allergy (FA) and the mechanisms of natural tolerance or induced desensitization are required. In addition, a detailed understanding of the pathophysiology of food allergies is needed to generate compelling, enduring, and safe treatment options. New findings regarding the contribution of barrier function, the effect of emollient interventions, mechanisms of allergen recognition, and the contributions of specific immune cell subsets through rodent models and human clinical studies provide novel insights. With the first approved treatment for peanut allergy, the clinical management of FA is evolving toward less intensive, alternative approaches involving fixed doses, lower maintenance dose targets, coadministration of biologicals, adjuvants, and tolerance-inducing formulations. The ultimate goal is to improve immunotherapy and develop precision-based medicine via risk phenotyping allowing optimal treatment for each food-allergic patient.

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.)

MRNA lipid nanoparticles induce immune tolerance to treat human diseases.

Rapid developments in the coronavirus disease 2019 (COVID-19) mRNA vaccine showcased the power of lipid nanoparticle (LNP) delivery systems in fighting infectious diseases. In addition, mRNA therapeutics are also in development for cancer immunotherapy. Recently, mRNA therapy has been expanded to induce immune tolerance, the opposite of immune-boosting effects, to treat diseases involving enhanced immune responses including allergies and autoimmune diseases. mRNA LNPs have been used to treat peanut allergy by us and autoimmune experimental autoimmune encephalomyelitis by Ugur Sahin. It is expected that more and more research is going to delve into the immune tolerance field for allergies and autoimmune diseases, where effective therapies are in short supply.

The next generation virus-like particle platform for the treatment of peanut allergy.

Allergy to peanut is one of the leading causes of anaphylactic reactions among food allergic patients. Immunization against peanut allergy with a safe and protective vaccine holds a promise to induce durable protection against anaphylaxis caused by exposure to peanut. A novel vaccine candidate (VLP Peanut), based on virus-like particles (VLPs), is described here for the treatment of peanut allergy. VLP Peanut consist of two proteins: a capsid subunit derived from Cucumber mosaic virus engineered with a universal T cell epitope (CuMVTT ) and a CuMVTT subunit fused with peanut allergen Ara h 2 (CuMVTT -Ara h 2), forming mosaic VLPs. Immunizations with VLP Peanut in both naïve and peanut-sensitised mice resulted in a significant anti-Ara h 2 IgG response. Local and systemic protection induced by VLP Peanut were established in mouse models for peanut allergy following prophylactic, therapeutic and passive immunizations. Inhibition of FcγRIIb function resulted in a loss of protection, confirming the crucial role of the receptor in conferring cross protection against peanut allergens other than Ara h 2. VLP Peanut can be delivered to peanut-sensitized mice without triggering allergic reactions, whilst remaining highly immunogenic and offering protection against all peanut allergens. In addition, vaccination ablates allergic symptoms upon allergen challenge. Moreover, the prophylactic immunization setting conferred the protection against subsequent peanut-induced anaphylaxis, showing the potential for preventive vaccination. This highlights the effectiveness of VLP Peanut as a prospective break-through immunotherapy vaccine candidate towards peanut allergy. VLP Peanut has now entered clinical development with the study PROTECT.

Dose and route of administration determine the efficacy of prophylactic immunotherapy for peanut allergy in a Brown Norway rat model.

Allergen-specific immunotherapy (IT) is emerging as a viable option for treatment of peanut allergy. Yet, prophylactic IT remains unexplored despite early introduction of peanut in infancy was shown to prevent allergy. There is a need to understand how allergens interact with the immune system depending on the route of administration, and how different dosages of allergen may protect from sensitisation and a clinical active allergy. Here we compared peanut allergen delivery via the oral, sublingual (SL), intragastric (IG) and subcutaneous (SC) routes for the prevention of peanut allergy in Brown Norway (BN) rats. BN rats were administered PBS or three different doses of peanut protein extract (PPE) via either oral IT (OIT), SLIT, IGIT or SCIT followed by intraperitoneal (IP) injections of PPE to assess the protection from peanut sensitisation. The development of IgE and IgG1 responses to PPE and the major peanut allergens were evaluated by ELISAs. The clinical response to PPE was assessed by an ear swelling test (EST) and proliferation was assessed by stimulating splenocytes with PPE. Low and medium dose OIT (1 and 10 mg) and all doses of SCIT (1, 10, 100 µg) induced sensitisation to PPE, whereas high dose OIT (100 mg), SLIT (10, 100 or 1000 µg) or IGIT (1, 10 and 100 mg) did not. High dose OIT and SLIT as well as high and medium dose IGIT prevented sensitisation from the following IP injections of PPE and suppressed PPE-specific IgE levels in a dose-dependent manner. Hence, administration of peanut protein via different routes confers different risks for sensitisation and protection from peanut allergy development. Overall, the IgE levels toward the individual major peanut allergens followed the PPE-specific IgE levels. Collectively, this study showed that the preventive effect of allergen-specific IT is determined by the interplay between the specific site of PPE delivery for presentation to the immune system, and the allergen quantity, and that targeting and modulating tolerance mechanisms at specific mucosal sites may be a prophylactic strategy for prevention of peanut allergy.

Харчова алергія. Сучасний погляд на діагностику та лікування

Abstract. Food allergy is an urgent health care problem. The incidence of food allergies has been increasing since the 1990s. The main factors contributing to the emergence of food allergies are presented: the hygienic hypothesis; sibling effect; the theory of double allergen exposure, etc. The gut microbiome plays a role in the pathogenesis and the course of food allergy. Patients with food allergy have distinct gut microbiomes compared to healthy controls. The development of food allergy is preceded by an imbalance of the intestinal microbial ecosystem. Diet, probiotics, prebiotics, symbiotics, and faecal microbiota transfer are potential microbial therapeutics for the prevention and treatment of food allergy. Diseases and syndromes associated with food allergy are considered. Diseases and syndromes associated with food allergy are considered. The main methods of food allergy diagnosis are provided: skin prick tests, laboratory serum tests, oral provocation test. Changing perceptions about the treatment of food allergies: treating food allergies with different methods of specific immunotherapy instead of avoiding allergenic foods. The FDA has already approved the oral immunotherapy treatment of peanut allergy with Palforzia AR101 allergen. The article lists the main drugs for medical treatment of food allergies, in particular omalizumab. Patients with food allergies should always carry an epinephrine injection device, which is the mainstay of pharmacotherapy for anaphylaxis.

Treatment of peanut allergy and colitis in mice via the intestinal release of butyrate from polymeric micelles

The microbiome modulates host immunity and aids the maintenance of tolerance in the gut, where microbial and food-derived antigens are abundant. Yet modern dietary factors and the excessive use of antibiotics have contributed to the rising incidence of food allergies, inflammatory bowel disease and other non-communicable chronic diseases associated with the depletion of beneficial taxa, including butyrate-producing Clostridia. Here we show that intragastrically delivered neutral and negatively charged polymeric micelles releasing butyrate in different regions of the intestinal tract restore barrier-protective responses in mouse models of colitis and of peanut allergy. Treatment with the butyrate-releasing micelles increased the abundance of butyrate-producing taxa in Clostridium cluster XIVa, protected mice from an anaphylactic reaction to a peanut challenge and reduced disease severity in a T-cell-transfer model of colitis. By restoring microbial and mucosal homoeostasis, butyrate-releasing micelles may function as an antigen-agnostic approach for the treatment of allergic and inflammatory diseases.

Long Non-Coding RNAs Expressed in the Peanut Allergy for Understanding the Pathophysiology of Peanut Allergy Rat Model

Peanut allergy (PA) has become a clinical and public health problem, which is mainly regulated by genetics, immune responses, and environmental factors. Diagnosis and treatment for PA have always remained huge challenges due to its multiple triggers. Studies have shown that long non-coding RNAs (lncRNAs) play a critical role in the development of allergic diseases. In the current study, we examined the plasma lncRNA expression profiles of peanut allergy Brown Norway rats and healthy controls and 496 differently expressed lncRNAs were identified, including 411 up-regulated genes and 85 down-regulated genes. We screened 8 lncRNAs based on the candidate principle and the candidates were verified in individual samples by quantitative real-time PCR. Then, the four lncRNA-based diagnostic model was established by least absolute shrinkage and selection operator (LASSO) and logistic regression, which was proved by area under the receiver operating characteristic curve (AUC). In summary, we assessed the correlation between lncRNA expression levels and the diagnosis of peanut allergy, which may perform a vital role in guiding the management of peanut allergy.

NON-CLINICAL SAFETY EVALUATION OF A NOVEL THERAPEUTIC VACCINE FOR PEANUT ALLERGY

<h3>Introduction</h3> Peanut allergy is the most common cause of fatal food-associated anaphylaxis. VLP Peanut is a novel virus-like particle (VLP)-based vaccine being developed for the treatment of peanut allergy. Prior to first in human trials, its safety was assessed in a repeat dose toxicology study. <h3>Methods</h3> VLP Peanut was administered with or without the adjuvant 1.95% MicroCrystalline Tyrosine, subcutaneously, to Wistar Han rats three times daily (TID) once every 4 weeks for 12 weeks as described (Fig 1). A maximum dose level of 3.6 mg was evaluated (anticipated maximum dose in humans). Assessment of toxicity included clinical, post-dose, and dose site observations; body weights; food consumption; ophthalmic observations; and clinical and anatomic pathology. <h3>Results</h3> Minor changes in bodyweight gains, food consumption and clinical pathology were noted in animals administered VLP Peanut ±MCT and minor, non-adverse, increases in spleen and liver weights were noted in some female animals. These changes were reversible and not adverse. Animals administered VLP Peanut ± MCT had occasional dose site observations of very slight or slight edema, more frequently noted for animals administered MCT. Macroscopic observations at subcutaneous injection site/s were noted for all test article-treated groups, which correlated with microscopic observations of inflammation and neutrophilic reactions at the subcutaneous injection site/s. Dose site observations were considered adverse but were fully reversed after a 4week recovery. <h3>Conclusion</h3> VLP Peanut administered to rats, was systemically well tolerated, with only minor, non-adverse clinical changes. Slight dose site observations were fully-reversible and did not impact on the overall health of the animals.

Current insights: a systemic review of therapeutic options for peanut allergy.

With increasing prevalence of peanut allergy (PA) globally and the greater risk of potential reactions occurring due to the leading role of nuts in food products, PA has become a significant public health concern over the past decade, affecting up to 5 million of the US adult population. This review details updates and advances in prevalence, diagnosis, and immunotherapies that have occurred over the past year. Therapeutic and diagnostic advances remain at the forefront of research and have continued to push the food allergy (FA) field forward to provide a promising role in the detection and treatment of PA. The FA field has researched significant advances in peanut immunotherapy, biomarker diagnosis, and quality of life (QoL) improvement. Given the burden and consequences for individuals with PA, these advances delivered in clinical practice can significantly improve the QoL of individuals with PA and their caregivers. Ongoing studies will continue to investigate long-term outcome measures of desensitisation and effective management plans tailored to the families' needs.

Health-related quality of life outcomes in a Phase 2b Randomized Trial evaluating the effectiveness and safety of Probiotic Peanut Oral Immunotherapy

Food allergy significantly impacts health-related quality of life (HRQL) of patients and their families. Treatments that can induce clinical remission are expected to improve HRQL. The Probiotic Peanut Oral ImmunoTherapy (PPOIT-003) multi-center randomized trial evaluated the impact of a novel peanut allergy treatment on HRQL out to 12-months post-treatment.

Outcomes of real-world use of FDA-approved peanut oral immunotherapy

In January 2020, the FDA approved oral immunotherapy (OIT) for the treatment of peanut allergy in children ages 4 to 17. In June 2020, our clinic began offering FDA-approved peanut OIT with Palforzia. We report the real-world application of FDA-approved peanut OIT at a tertiary care pediatric center.