Immunotherapeutic Approaches to Peanut Allergy Treatment-Pre-Clinical and Clinical Studies: A Comprehensive Review
Peanut allergy is a prevalent and potentially life-threatening condition affecting millions of people worldwide, necessitating strict dietary vigilance. Despite its widespread impact, current treatment options are predominantly limited to allergen avoidance and emergency management of allergic reactions. This review explores contemporary immunotherapeutic strategies aimed at achieving long-term relief for individuals with peanut allergy. We conducted a comprehensive literature review to discuss different treatment approaches, such as subcutaneous immunotherapy (SCIT), epicutaneous immunotherapy (EPIT), oral immunotherapy (OIT), and sublingual immunotherapy (SLIT), focusing on their mechanisms, efficacy, and safety profiles. Additionally, the review delves into novel approaches such as monoclonal antibodies targeting IgE and other critical immune pathways, adjuvanted therapies utilizing nanoparticles and gut microbiota, and advances in adoptive cell therapy including CAR-T cells and regulatory T cells. Furthermore, we highlight some clinical trials that test the efficacy and safety of these novel immunotherapeutic approaches in patients with peanut allergy. Collectively, we provide an overview of advancements in immunotherapeutic interventions for peanut allergy and recommendations for personalized immunotherapy regimens, ultimately paving the way for more effective treatment strategies.
https://doi.org/10.3390/jcm14061902
Peanut challenges prior to oral immunotherapy demonstrate high tolerance rates in selected patients
Background: Peanut oral immunotherapy (pOIT) protocols typically remain below the threshold for reaction during the initial dose escalation (IDE) day. However, some patients may have higher thresholds for reaction or may not have an ongoing peanut allergy. Objective: We sought to characterize the response to an accelerated initial dose escalation (A-IDE) for qualifying low-risk peanut-allergic patients younger than 4 years in which IDE progressed to a full peanut oral food challenge as tolerated. Methods: Records of 76 pOIT patients younger than 4 years were reviewed. Those with history of peanut reaction with peanut allergy testing of less than 95% positive predictive value for failed oral food challenge were offered an A-IDE. A-IDE proceeded stepwise until patients refused dosing, any reaction occurred, or they tolerated the challenge (cumulative dose: 4000 mg peanut protein). If the A-IDE was not tolerated, patients completed pOIT. Results: From April 2022 to February 2024, 16 patients participated in an A-IDE. Eleven (68.8%) tolerated the 4000 mg cumulative dose, demonstrating resolution of their peanut allergy. The remaining had mild symptoms not requiring epinephrine. Mean pOIT starting dose following A-IDE was 450 mg (vs 25 mg in standard pOIT). Maintenance dosing was reached with a mean of 5.2 visits (vs 9.7 in standard pOIT). Conclusions: Nearly 70% of low-risk patients younger than 4 years with previous diagnosis of peanut allergy tolerated a full peanut serving when initiating pOIT. This indicates the importance of diagnostic peanut challenge to selected patients before initiating OIT.
https://doi.org/10.1016/j.jacig.2025.100442
Update on hazelnut allergy: Allergen characterization, epidemiology, food processing technique and detecting strategy
Hazelnuts are popular among people due to their dense nutrient component. However, eating them may be quite dangerous for those who are allergic. To improve food safety, this research examines current developments in the characterization, processing, and detection of hazelnut allergens. The identification and molecular knowledge of certain proteins that cause allergic responses are necessary for the characterization of hazelnut allergens. Proteomics and genomics are two techniques that have helped to advance our knowledge of hazelnut allergens and facilitate the creation of more precise diagnostic instruments. One important factor to reduce but not to eliminate the exposure to hazelnut allergens is food processing. The extractability of hazelnut proteins with regard to food processing plays a crucial role in determining allergenicity. Innovative technologies have been created to lessen allergenicity in foods containing hazelnuts while preserving their flavor and quality. These technologies include thermal and nonthermal processing techniques. To further safeguard consumers with hazelnut allergies, innovations in ingredient labeling and cross-contamination avoidance techniques have been put into place. For the purpose of management, if foods contain hazelnut, they must label it. Technological developments in analytical methods, including mass spectrometry, polymerase chain reaction, and enzyme-linked immunosorbent assays, have made it possible to identify hazelnut allergens with high specificity and sensitivity in a range of dietary matrices. Moreover, the advancement of point-of-care testing instruments presents the possibility of prompt on site identification, hence enhancing food safety for people with hazelnut allergies. The multidisciplinary efforts of researchers, food technologists, and allergists to enhance the safety of products containing hazelnuts are highlighted in this study.
https://doi.org/10.1111/1541-4337.70098
Efficacy and Safety of Epicutaneous Immunotherapy in Peanut-allergic Children with Atopic Comorbidities
Background: There is a high prevalence rate of atopic comorbidities, including atopic dermatitis (AD), asthma, and concomitant food allergy (CFA), in children with peanut allergy. Objective: To evaluate whether concomitant atopic comorbidities affect the safety and efficacy of VIASKIN® peanut patch (VP250). Methods: EPITOPE was a phase 3, double-blind, placebo-controlled trial designed to assess treatment response to VP250, as measured by eliciting dose at 12 months, in peanut-allergic children aged 1 through 3 years. This subgroup analysis assessed response rates for prespecified subgroups, including children with asthma, AD/eczema, and CFA. The safety profile of VP250 was evaluated by atopic condition in all randomized participants who received at least 1 dose. Results: Responder rates were significantly greater with VP250 vs placebo, irrespective of the presence of atopic conditions. There was no significant interaction effect between participants with an atopic comorbidity vs those without. The safety profile was generally similar across subgroups without any additional safety signals. There was no clinically meaningful change in severity of AD in those receiving VP250, regardless of baseline AD status. Rates of anaphylaxis were higher in those with AD or CFA receiving VP250 vs those without; however, these imbalances were also observed in the placebo group. Conclusion: The results suggest that 12 months of treatment with VP250 was effective in desensitizing peanut-allergic children aged 1 through 3 years, with no difference in efficacy and a favorable safety profile, regardless of the presence of atopic comorbidities.
https://doi.org/10.1016/j.anai.2025.04.002
Maternal supplementation with α-tocopherol inhibits the development of offspring food allergy, H1R signaling and ultimately anaphylaxis early in life
Food allergy has had a rapid rise in prevalence, and thus it is important to identify approaches to limit the development of food allergy early in life. Because maternal dietary supplementation with α-tocopherol (α-T), an isoform of vitamin E, during pregnancy and nursing increases neonate plasma levels of α-T and can limit neonate development of other allergies, we hypothesized that α-T can limit development of food allergy. To assess this, male mice with mutations in their skin barrier genes (FT−/− mice) were mated with wild-type females that received a diet supplemented with α-tocopherol or a control diet. Starting at postnatal day 3, these FT+/− pups were sensitized 4 to 5 times over 2.5 weeks by skin co-exposure to the food allergen peanut extract (PNE) and the environmental allergen Alternaria alternata (Alt). Control pups were exposed to saline, PNE only or Alt only. Supplementation with α-T blocked Alt+PNE sensitization (anti-PNE-specific IgE), without blocking Alt+PNE-stimulated skin IL33, Areg, OSM, CCL11, TSLP or plasma MCPT1. However, supplementation with α-T blocked mast cell activation, the increase in plasma histamine in Alt+PNE sensitized pups, histamine receptor stimulation of endothelial PKCα signaling, and ultimately oral PNE-induced anaphylaxis in Alt+PNE sensitized mice. Thus, maternal supplementation with α-tocopherol reduced development of food allergy and anaphylaxis in neonates. These results have implications for supplementation of mothers with α-tocopherol to limit development of food allergy in neonates with skin barrier mutations.
https://doi.org/10.1093/jimmun/vkae041
Enhancing the diagnostic accuracy of the IgE crosslinking-induced luciferase expression (EXiLE) method for walnut allergy
Background: Walnut (Juglans regia) frequently triggers nut allergies in the United Kingdom and in the United States, with increasing cases in Japan. While oral food challenges (OFCs) are the definitive method for diagnosing these allergies, they pose the risk of symptom provocation, necessitating safer alternative tests. Our aim here was to evaluate the diagnostic utility of IgE (immunoglobulin E) crosslinking-induced luciferase expression (EXiLE) for walnut allergy compared with the walnut-specific IgE (sIgE) test, Jug r 1-sIgE test, and skin prick test (SPT). Methods: This retrospective study analyzed 55 patients tested for walnut allergy (WA) at Fujita Health University Bantane Hospital from January 2021 to December 2023. Among them, 38 had allergic reactions to walnuts based on history or OFCs and 17 did not. We evaluated the sensitivity, specificity, positive predictive value, negative predictive value, and the area under the curve (AUC) of the receiver operating characteristic curve. Results: The EXiLE method (AUC = 0.938) exhibited superior diagnostic accuracy compared to the walnut-sIgE and comparable performance to Jug r 1-sIgE and SPT. The optimal cutoff value of 1.26-fold change demonstrated high sensitivity (0.92), specificity (0.88), positive predictive value (0.92), and negative predictive value (0.82). The EXiLE method yielded positive results in all three cases with negative Jug r 1-sIgE (< 0.35 UA/mL). Conclusion: The EXiLE method showed high sensitivity and specificity for diagnosing WA, indicating its potential clinical utility. Furthermore, the combination of Jug r 1-sIgE and EXiLE may enhance diagnostic accuracy. Future large-scale studies are warranted to confirm these findings and establish comprehensive diagnostic protocols.
https://doi.org/10.15586/aei.v53i2.1267
The prevalence of peanut-triggered food protein-induced enterocolitis syndrome in a prospective cohort of infants introducing peanut in the first year of life
Background: Since the early introduction of peanut to prevent IgE-mediated peanut allergy, other case series have suggested an increased incidence of peanut-triggered Food Protein Induced Enterocolitis Syndrome (FPIES). Data on the prevalence of peanut-induced FPIES in prospective cohorts are lacking. Methods: The PeanutNL cohort is a prospective cohort that included infants at risk of peanut allergy (n = 706) as well as infants with reactions to peanut at home after early introduction (n = 186). They all introduced peanut before the age of 12 months. Oral food challenges were performed to introduce peanut or to evaluate reactions to peanut at home. Results: Of the 706 infants that were included for first introduction of peanut, 2 had reactions with a phenotype compatible with FPIES (0.3%). Of the 186 infants with reactions to peanut at home, 6 were diagnosed with FPIES (3.2%). Seven out of 8 cases had ingestions of peanut without reactions at home or during clinical introduction before FPIES became apparent. During a 3-year follow-up, six infants (75%) were shown to be tolerant to peanut before the age of 3 years. Conclusion: The prevalence of challenge-proven peanut-induced FPIES in a Dutch cohort of atopic infants that introduced peanut between the ages of 4 and 11 months is 0.3%. The majority of cases were tolerant to peanut before the age of 3 years. When introducing peanut in the first year of life, physicians should be aware of FPIES reactions, but it should not be a reason to avoid early introduction of peanut.
https://doi.org/10.1111/pai.70058
Basophil Activation Test for the Improved Diagnosis of Peanut and Tree Nut Allergy
Purpose of review: As an ex-vivo test of allergic effector cell activation, basophil activation testing (BAT) to allergen enables quantification of the in-vivo IgE-mediated allergic response. BAT thus holds promise in the diagnosis and monitoring of peanut and tree nut allergies. Recent systematic analyses and expert recommendations support a role for BAT in the diagnosis of peanut and tree nut allergy. Recent findings: Diagnostic cut-offs for BAT in peanut and tree nut allergy have been identified. Consistently, BAT can discriminate with high sensitivity and specificity between allergy and tolerance when measured against oral food challenges. Furthermore, the utilization of BAT has can increase the sensitivity and specificity of peanut allergy and tree nut allergy diagnosis, both alone and in conjunction with specific IgE testing and skin prick testing. BAT is a promising tool in the diagnosis of peanut and tree nut allergy.
https://doi.org/10.1007/s11882-025-01200-1
Efficacy and Safety of Epicutaneous Immunotherapy in Peanut-Allergic Toddlers: Open-Label Extension to EPITOPE
Background: The pivotal phase 3 EPITOPE trial, a 12-month, double-blind, placebo-controlled study of epicutaneous immunotherapy with the VIASKIN® patch containing 250 μg peanut protein (VP250) previously reported significant treatment response vs placebo in peanut-allergic toddlers aged 1-through-3 years. Objective: To assess interim efficacy and safety of VP250 from the first year of the EPITOPE open-label extension (OLE) study. Methods: Eligible participants enrolled in the OLE study for up to 3 years of total treatment with annual double-blind, placebo-controlled food challenges (DBPCFC) and safety assessments; here we report the first year OLE (Year 2) results. Results: 266 EPITOPE participants enrolled in the OLE study; 244 underwent Month 24 DBPCFC (n=166 VP250; n=78 placebo). After 24 months of VP250, 81.3% reached an eliciting dose (ED) ≥1000 mg, 63.8% reached an ED ≥2000 mg, and 55.9% completed the DBPCFC (cumulative dose: 3444 mg) without meeting stopping criteria. No treatment-related anaphylaxis or serious treatment-related adverse events occurred during Year 2 in this treatment arm. Local application-site reactions occurred less frequently in Year 2 vs Year 1. In placebo-treated EPITOPE participants, outcomes after 1 year of open-label VP250 were consistent with EPITOPE treatment results: 62.7% reached an ED ≥1000 mg, 36.5% reached an ED ≥2000 mg, and 28.4% completed the DBPCFC without meeting stopping criteria; and there was 1 treatment-related anaphylaxis event. Conclusions: Two years of VP250 in young peanut-allergic children demonstrated continued treatment effect increases without new safety signals. This supports the potential of VP250 as a safe and effective treatment for peanut allergy in young children.
https://doi.org/10.1016/j.jaip.2025.02.004
Hazelnut oral immunotherapy desensitizes hazelnut but not other tree nut allergies (Nut CRACKER Study)
Background: Data on oral immunotherapy (OIT) for hazelnut allergy is limited and its potential to cross-desensitize for other nuts is unknown. Objective: To study the efficacy and safety of hazelnut OIT in desensitizing hazelnut and additional tree nuts. Methods: A prospective observational study of 30 hazelnut allergic patients aged ≥4 years who underwent hazelnut OIT. Full desensitization (4000 mg protein) rates were compared to 14 observational controls, and immunological changes during OIT were measured. Cross-desensitization was determined in cases of walnut and cashew co-allergy (n=12). Inhibition of IgE binding to walnut by hazelnut was evaluated in a separate set of walnut-hazelnut dual allergic patients, by ELISA. Results: The rate of full hazelnut desensitization following OIT was 96.7% (29/30) compared to 14.3% (2/14) in controls (OR=25.7, 95% CI 3.7-178.7, p<0.001). Five patients (16.7%) were treated with injectable epinephrine for home reactions. Hazelnut SPT and sIgE to hazelnut and its main components, Cor a 9, 14 and 16, decreased while sIgG4 increased during OIT. A maintenance dose of 1200 mg hazelnut protein was sufficient to maintain full desensitization. No cross-desensitization was noted in dual hazelnut-cashew allergic patients (n=6). In dual hazelnut-walnut allergic patients, an increase in the walnut eliciting dose was observed in 2/6 (33.2%) patients (to 1200 and 4200 mg, respectively). Similarly, by cross-inhibition ELISA, hazelnut competed for IgE-binding to walnut in 5/25 (20%) hazelnut-walnut co-allergic patients. Conclusions: Hazelnut OIT is highly effective, with a similar safety profile as OIT to other nuts. Cross-desensitization to walnut and cashew is unlikely.
https://doi.org/10.1016/j.jaip.2024.12.041