Induction of regulatory T cells by an aluminum-CpG combination adjuvant for therapeutic and preventive vaccination against pollen allergy.

Hyaluronic acid-based microneedles: materials design, fabrication strategies, challenges, and solutions for biomedical applications.

Feline Asthma-Update on Diagnosis and Treatment Recommendations.

Cassava oral immunotherapy in cassava-latex allergy: A pilot study.

Tropomyosin (TM), a major allergen in Oratosquilla oratoria with strong immunobinding activity, underscores the importance of allergen-specific immunotherapy, for which hypoallergenic derivatives represent a promising strategy. In this study, the derivatives of TM from O. oratoria were prepared by selective deletion of B-cell epitopes and retention of T-cell epitopes and were named mTM. The hypoallergenicity of mTM was further confirmed in a mouse model of food allergy. Furthermore, the prophylactic efficiency of mTM was evaluated in a prophylactic mouse model for O. oratoria allergy. It was shown that mTM simultaneously attenuated IgE-mediated allergic responses, alleviated allergic responses via regulating Th1/Th2 balance, and enhanced the ratio of regulatory T cell-associated cytokines. Overall, the study provides a theoretical basis and research direction for the development of hypoallergenic derivatives for prophylactic administration in food allergies.

Ultra-short recombinant Art v 1 immunotherapy induces rapid immune modulation in mugwort allergy: A Phase I trial.

Allergic disorders, including food allergy, asthma, and atopic dermatitis, affect an estimated 10-30% of the global population, with prevalence continuing to rise in industrialized countries. Allergy is driven by dysregulated type 2 T-helper cells (Th2) and immunoglobulin E (IgE) antibody responses. A range of diagnostic tools is available, but most methods are limited by variable sensitivity and specificity, and the inability to predict clinical reactivity. Although allergen-specific immunotherapy (AIT) remains the only etiological therapeutic method for allergic disorders, conventional AITs are limited by frequent administration, risk of adverse events, suboptimal patient adherence, and inconsistent long-term efficacy. Advances in nanotechnology offer emerging opportunities for improving allergy diagnosis and treatment through enhanced analytical sensitivity, targeted allergen delivery and controlled immune modulation. This review provides a comprehensive overview of the latest research on nanomaterials, including their application in nanomaterials-based diagnostic systems and nano-enabled immunotherapies. We highlight their roles in improving allergen-specific IgE detection, refining functional cellular assays, and enabling next-generation immunotherapies through controlled allergen delivery and immunomodulation. We also critically examine key translational barriers and outline essential future directions required for translating nanotechnologies into clinical practice in allergy medicine.

Comparative Efficacy of Subcutaneous and Sublingual Allergen Immunotherapy for Grass Pollen-Induced Allergic Rhinoconjunctivitis: Pairwise and Adjusted Indirect Treatment Comparison of Standardized ALK Products.

ABSTRACTBackgroundMultiple routes of allergen immunotherapy (AIT) are approved for several IgE‐mediated allergic diseases; however, the use of AIT in eosinophilic esophagitis (EoE) remains controversial and is supported by limited evidence. This review, conducted within the frame of an EAACI Task Force, aims to systematically evaluate the use of AIT as a potential treatment for EoE.MethodsThe protocol was registered and prepared in accordance with PRISMA guidelines. The literature search was conducted across three online databases (PubMed, Embase, and Scopus) and included studies published through January 31st, 2025. Risk of Bias was assessed for each eligible study.ResultsFour articles met the inclusion criteria. Three articles evaluated EPIT for milk‐induced EoE in pediatric patients, all from the SMILEE (Study of Efficacy and Safety of Viaskin Milk for milk‐induced EoE) trial and its extensions. These included a randomized, placebo‐controlled trial, its open‐label extension, and a pilot immunological study. The SMILEE trial found no statistically significant difference in tissue eosinophilia between the active (EPIT) and control (placebo) arms in the intention‐to‐treat population, while 47% of treated EoE patients tolerated milk without recurrence of esophageal eosinophilia. This finding was further supported by a subsequent open‐label study with a 2‐year follow‐up. In the third publication, the researchers found that EPIT was associated with decreased Th2‐related transcripts and increased regulatory T‐cell‐associated transcripts. Only one eligible study evaluated the use of SCIT for treating EoE. It was a retrospective case‐control study reporting that SCIT had a neutral effect and yielded inconclusive findings regarding the course of EoE.ConclusionThere is insufficient high‐quality evidence to support the effectiveness of alternative routes of AIT for the treatment of EoE, either as an add‐on or a standalone treatment.

The therapeutic goal in chronic airway diseases is shifting from symptom control to disease remission. Disease-modifying therapies, including biologics and allergen immunotherapy, have made remission achievable in patients with severe asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), or allergic rhinitis (AR). This EUFOREA consensus aims to establish practical guidance for inducing and maintaining remission in global airway diseases. An international panel of experts in pneumology, rhinology, and allergology convened in Rome (October 2025) to review current evidence and develop consensus statements. The panel achieved consensus on key principles: (i) remission is a therapeutic target independent of disease severity prior to treatment initiation and should not be reserved for severe cases; (ii) CRSwNP with nonallergic eosinophilic asthma, and AR with allergic asthma should be considered features of a single disease rather than comorbidities; (iii) remission should be assessed by each subspecialty separately while warranting combined approaches; (iv) pragmatic definitions prioritizing achievability and clinical utility are recommended; and (v) a 4-week recall window is preferred to assess symptom control within the evaluation of remission and a 12-month period is suggested as the minimal period to define remission. Remission represents an ambitious yet achievable goal, with practical guidance for optimizing patient outcomes.

The development of pathogen-associated molecular patterns (PAMPs) that signal via pathogen recognition receptors (PRRs) on innate immune cells is a strategy that is widely adopted in adjuvant research. Less well studied is how covalently linking different PAMPs affects the immune response. Herein, we summarise the research on the effect of PAMP linkage on innate and adaptive immune responses. These covalently linked or "chimeric" PAMPs often lead to immune cell synergies that are greater than those exhibited by the admixed (unconjugated) PAMPs, with several PAMP conjugates exhibiting remarkable adjuvant activity in a variety of disease contexts that include infectious disease, allergy, and cancer immunotherapy. This improvement in immune cell activation is thought to be due to more effective crosstalk between the different PRR signalling pathways, as conjugation ensures that each cell receives each class of PAMP. In addition, PAMP conjugates can form particulates, which has been postulated to lead to improved adjuvanticity, or they may facilitate the targeting of endosomal PRRs via the PRR-mediated endocytosis of the alternative PAMP in the conjugate. PAMP conjugates can also reduce the toxicity of individual PAMPs. However, not all PAMP conjugates are effective, and there are still many aspects of this research platform that are poorly understood, including how linker chemistry affects the immune response and how PRR signalling pathways or PAMP combinations combine to skew the immune response. We will address these and other outstanding questions that relate to the use of PAMP conjugates as vaccine adjuvants.

Allergic diseases continue to increase globally, and accumulating evidence implicates early-life microbial exposures as central determinants of immune tolerance. This review synthesizes advances from 2024 to 2026 regarding probiotic-mediated immune modulation and their translational implications in allergy prevention and therapy. Recent studies confirm strain-specific expansion of Foxp3+ regulatory T cells, suppression of Th2 polarization, reinforcement of epithelial barrier integrity, and durable epigenetic stabilization mediated by short-chain fatty acids such as butyrate. Clinical trials demonstrate benefit in perinatal prevention of atopic dermatitis, modulation of allergic rhinitis symptoms, early-life asthma risk reduction, and probiotic-adjuvanted oral immunotherapy. Probiotics are evolving from adjunctive supplements to biologically active immune modulators with disease-modifying potential. Integration with allergen immunotherapy and precision microbiome profiling may redefine preventive and therapeutic strategies in allergic disease.

House dust mite (HDM) allergy contributes to allergic rhinitis and asthma worldwide. Allergen-specific immunotherapy (AIT) is the only disease-modifying treatment, with immunoglobulin G4 (IgG4) and regulatory T cells (Tregs) mediating immune tolerance. Comparative immunological effects of subcutaneous (SCIT) versus sublingual (SLIT) therapy remain underexplored. To evaluate immunological changes induced by SCIT and SLIT and their association with clinical improvement in HDM-allergic patients. In this prospective cohort, 43 adults with HDM-sensitized allergic patients received SCIT (n = 22) or SLIT (n = 21) for nine months. Clinical outcomes were assessed using the Asthma Control Test (ACT) and Rhinitis Control Assessment Test (RCAT). Serum IgG4 and total IgE were measured by ELISA and electrochemiluminescence, respectively, and CD4⁺CD25⁺FoxP3⁺ Tregs were analyzed by flow cytometry. Responders were defined as patients achieving ≥ 20% improvement in ACT or RCAT. Wilcoxon signed-rank, Mann–Whitney U, and Spearman correlation tests were used. AIT increased IgG4 (320 → 920 ng/mL; p < 0.001) and Tregs (3.4% → 6.3%; p < 0.001), with a non-significant decrease in IgE. Responders had higher IgG4 and Tregs and lower IgE than non-responders. SCIT elicited higher IgG4 levels (median 1035 vs 705 ng/mL) and a trend toward greater Treg expansion compared with SLIT, although clinical improvement was similar between groups. IgG4 correlated with ACT (p < 0.001) and RCAT (p = 0.002), and Tregs correlated positively with IgG4 (p = 0.003) and inversely with IgE (p = 0.010). Both SCIT and SLIT improve clinical outcomes in HDM-allergic patients via total IgG4 elevation and Treg expansion. SCIT may induce stronger systemic immunological responses, supporting the use of these biomarkers for early monitoring and personalized therapy. These findings should be interpreted within the context of a pilot study with a relatively small sample size.

Background and objectives: Food allergy, particularly peanut allergy, is a significant and growing health concern, especially in high-income countries. Affecting 2% of children and 1% of adults, peanut allergy is a chronic condition that severely impacts quality of life. The standard treatment remains allergen avoidance, though oral immunotherapy (OIT) has emerged as a potential strategy for desensitization. This systematic review and meta-analysis aims to evaluate the efficacy and safety of peanut oral immunotherapy (POIT) based on randomized controlled trials (RCTs). Methods: A systematic review and meta-analyses were conducted following PRISMA guidelines. Eligible studies included double-blind RCTs evaluating POIT versus placebo or avoidance. Databases such as PubMed, Google Scholar, Cochrane-Controlled Register of Trials, and ClinicalTrials.gov were searched. Risk of bias was assessed using the Cochrane Risk of Bias tool (ROB2), and statistical analysis was performed using the RevMan software. Results: A total of 20 studies with 2161 participants (median age: 8.6 years) were included. POIT demonstrated a significant increase in desensitization rates (RR = 7.25, 95% CI: 2.66–19.79, P = 0.0001). However, POIT was also associated with increased risks of anaphylaxis (RR = 2.27, 95% CI: 1.48–3.47, P = 0.0002) and epinephrine use (RR = 2.05, 95% CI: 1.35–3.12, P = 0.0008). Adverse effects such as gastrointestinal symptoms, respiratory events, and skin abnormalities were more frequent in the POIT group, leading to a higher treatment discontinuation rate (RR = 2.50, 95% CI: 1.20–5.21, P = 0.01). Conclusion: POIT is effective in inducing desensitization in peanut-allergic individuals but carries significant risks, including an increased likelihood of anaphylaxis and adverse events. These findings reinforce previous meta-analyses and highlight the need for individualized risk-benefit assessments in clinical practice. Further research is required to optimize treatment protocols and improve patient safety.

B cells contribute to the pathogenesis of food allergies as they induce allergen-specific antibody production. Clinically-used allergen-specific immunotherapies have shown to induce regulatory B cell (Bregs) subsets as well as target and reduce allergy-driving B cell functions. This report aims to elucidate the contribution of regulatory B cells to an allergen-encapsulating nanoparticle (aeNP) immunotherapy in a murine model of food allergy. In this model, B cells directly associated with aeNPs. CD20+ B cell depletion after aeNP treatment increased the number of mice with severe allergic reactions during oral food challenges and reduced the expansion of regulatory immune cells including CD103+ dendritic cells (DCs) and CCR9+ gut-homing regulatory T cells, indicating that B cells are a component of aeNP immunomodulation. B cell communication in the gastrointestinal tract of aeNP-treated mice identified CD23 signaling as a potential inducer of regulatory CD103+ DC functions and disrupter of allergy-driving B cell-T cell communication. These tolerogenic signaling patterns were also identified in IL-10+ B cells, which have been known to impart regulatory immune effects in both murine and human disease. Ultimately, B cells are a component of the complex immunomodulation leading to aeNP efficacy at reducing allergic reactivity.

Probiotic-Derived CpG-DNA Enhances Food Allergy Immunotherapy via TLR9-Dependent Breg Induction and IL-10 Epigenetic Activation.

Pumpkin seed, a member of the Cucurbitaceae family, is increasingly consumed because of its high protein content and perceived health benefits. Along with its growing use, cases of pumpkin seed allergy are being reported. However, data on pumpkin seed allergy and oral immunotherapy (OIT) remain scarce. We conducted a retrospective chart review at a tertiary pediatric center (Sainte-Justine University Hospital Center, Montreal, Canada) including all patients who initiated or completed pumpkin seed OIT since 2019. OIT protocols were individualized, with dose increases typically performed every four weeks. Target maintenance doses were at least 300mg of pumpkin seed protein. Eleven patients (median age at OIT initiation: 6.5years; range 1-12) underwent pumpkin seed OIT. Ten patients (91%) reached maintenance dosing within a median of 9.5months (range 6-22) while one patient discontinued OIT due to persistent abdominal pain. No anaphylactic reactions occurred at home during treatment. Two anaphylactic reactions requiring epinephrine occurred during in-clinic up-dosing visits in a single patient, despite this, the patient ultimately achieved maintenance. Gastrointestinal and oral symptoms were the most frequent adverse events and were generally managed with temporary premedication. Most patients (91%) underwent concomitant multi-food OIT. Patients with significant adverse reactions had high ratios of pumpkin-specific IgE to total IgE. Pumpkin seed OIT appears feasible in a highly atopic pediatric population, with a safety profile comparable to that reported for OIT to other food allergens. Given the increasing dietary exposure to pumpkin seeds, larger prospective studies are needed to better define risk factors and long-term outcomes.

The management of moderate-to-severe allergic rhinitis (AR) is challenging given numerous advanced therapies. A comparative, evidence-based treatment hierarchy to guide the selection of biologics, allergen immunotherapy (AIT), and advanced pharmacotherapies is critically lacking due to a paucity of head-to-head trials. This network meta-analysis established a treatment hierarchy for moderate-to-severe AR by comparing the efficacy and safety of biologics, AIT, and key pharmacotherapies. We analyzed 28 randomized controlled trials (13,312 participants), which evaluated the efficacy and safety of biologics (anti-IgE, anti-IL-4Rα therapies), AIT (evaluated within a 6-month time frame to ensure comparability), and key pharmacotherapies (intranasal corticosteroids alone or combined with antihistamines) for moderate-to-severe AR. Efficacy was assessed by changes in the Total Nasal Symptom Score (TNSS), the Total Ocular Symptom Score (TOSS), and the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). A treatment hierarchy was established using surface under the cumulative ranking curve (SUCRA) probabilities. For the TNSS, anti-IL-4Rα therapy was most effective, followed by anti-IgE therapy and AIT, which surpassed all pharmacotherapies. The combination of intranasal corticosteroid and intranasal antihistamine ranked the highest for ocular symptoms. Anti-IL-4Rα therapy was also superior for improving the RQLQ. Overall, all treatments demonstrated a favorable safety profile. Biologics and AIT did not show a significant increase in adverse events risk compared to placebo. This network meta-analysis establishes the first comprehensive treatment hierarchy for moderate-to-severe AR. Our findings demonstrate that biologics, particularly anti-IL-4Rα therapy, are the most effective interventions for nasal symptom control, ranking superior to AIT and pharmacotherapies, thus providing a robust, data-driven framework to personalize patient care.

This expert point of view discusses why allergen-specific immunotherapy (AIT) should be considered earlier in the management of allergic rhinitis and asthma, highlighting a shift from its traditional use as a last-line add-on therapy toward a more proactive, disease-modifying intervention in carefully selected patients. Large real-world datasets, including the REACT program and the EfficAPSI study, show that adding AIT to standard care in patients with allergic rhinitis, with or without mild-to-moderate asthma, is associated with sustained reductions in pharmacologic treatment needs, fewer severe asthma exacerbations, and lower healthcare utilization over long-term follow-up. Pediatric and adolescent analyses suggest that starting AIT earlier in life enhances these benefits, supporting the concept of a "window of opportunity" during which immune modulation may prevent or delay asthma onset and limit new sensitizations, in line with the notion of the allergic march. The accumulating real-world evidence that early AIT can alter the natural history of allergic airway disease provides a strong rationale to reposition AIT within clinical algorithms, moving it from a rescue option for pharmacologic failures to an earlier, integrated disease-modifying strategy. Earlier use of AIT, alongside optimized pharmacotherapy, may improve long-term control, reduce progression to severe asthma, with important implications for patients and health-care systems.

Allergic rhinitis imposes a substantial clinical and socioeconomic burden globally. While symptomatic pharmacotherapy such as oral antihistamines and intranasal corticosteroids offers temporary relief, allergen immunotherapy provides disease-modifying benefits but requires higher upfront costs. This systematic review synthesises cost-effectiveness evaluations of subcutaneous (SCIT) and sublingual immunotherapy (SLIT) compared to symptomatic pharmacotherapy (SP). A systematic search of electronic databases was undertaken, identifying 35 eligible economic evaluations. Due to methodological heterogeneity, a narrative synthesis was performed. Thirty-two evaluations (91%) concluded that allergen immunotherapy represents a cost-effective intervention, with incremental cost-effectiveness ratios predominantly falling below jurisdictional willingness-to-pay thresholds. Both SCIT and SLIT demonstrated economic value, particularly in patients with co-morbid asthma and when models incorporated sustained post-treatment benefits. Future clinical research should prioritise endpoints that facilitate direct estimation of health utility. Despite diverse healthcare settings and modelling approaches, the evidence supports allergen immunotherapy (AIT) as an economically rational investment. Policymakers should utilise these findings to inform reimbursement decisions. Trial Registration: PROSPERO registration number: CRD42024530911.