A modified grass allergen subcutaneous immunotherapy (SCIT) product with MicroCrystalline Tyrosine and monophosphoryl lipid-A as an adjuvant system (Grass MATA MPL [PQ Grass]) is being developed as short-course treatment of grass-pollen allergic rhinitis (SAR) and/or rhinoconjunctivitis. We sought to evaluate the combined symptom and medication score (CSMS) of the optimized cumulative dose of 27,600 standardized units (SU) PQ Grass in a field setting prior to embarking on a pivotal Phase III trial.

In this exploratory, randomized, double-blind, placebo-controlled trial subjects were enrolled across 14 sites (Germany and the United States of America). Six pre-seasonal subcutaneous injections of PQ Grass (using conventional or extended regimens) or placebo were administered to 119 subjects (aged 18-65 years) with moderate-to-severe SAR with or without asthma that was well-controlled. The primary efficacy endpoint was CSMS during peak grass pollen season (GPS). Secondary endpoints included Rhinoconjunctivitis Quality of Life Questionnaire standardized (RQLQ-S) and allergen-specific IgG4 response.

The mean CSMS compared to placebo was 33.1% (p = .0325) and 39.5% (p = .0112) for the conventional and extended regimens, respectively. An increase in IgG4 was shown for both regimens (p .01) as well as an improvement in total RQLQ-S for the extended regimen (mean change -0.72, p = .02). Both regimens were well-tolerated.

This trial demonstrated a clinically relevant and statistically significant efficacy response to PQ Grass. Unprecedented effect sizes were reached for grass allergy of up to ≈40% compared to placebo for CSMS after only six PQ Grass injections. Both PQ Grass regimens were considered equally safe and well-tolerated. Based on enhanced efficacy profile extended regime will be progressed to the pivotal Phase III trial.

Although it has been shown that allergen immunotherapy (AIT) is well-tolerated in children, systematic and prospective surveillance of AIT safety in real life settings is needed.

The multinational Allergen Immunotherapy Adverse Events Registry (ADER) was designed to address AIT safety in real life clinical practice. Data on children ≤18 years old with respiratory allergies undergoing AIT were retrieved. Patient- and AIT-related features were collected and analyzed. The characteristics of adverse events (AE) and risk factors were evaluated.

A total of 851 patients, 11.3 ± 3.4 years old, with rhinitis only (47.6%); asthma and rhinitis (44.5%); asthma (7.9%), receiving 998 AIT courses were analyzed. Sublingual immunotherapy (SLIT) accounted for 51% of the courses. In 84.5% of patients only one AIT treatment was prescribed. Pollen was the most frequent sensitizer (57.1%), followed by mites (53.4%), molds (18.2%) and epithelia (16.7%). Local and systemic AEs were reported in 85 patients (9.9%). Most AEs (83.1%) were mild and occurred in <30 min (87%). Respiratory and cutaneous symptoms were more frequent. Only 4 patients (0.47%) had severe AE (none after 6 weeks of maintenance). The risk of AE was higher in patients undergoing SCIT.

AIT is safe and well tolerated in children and adolescents with respiratory allergies in real-life clinical practice. Though SCIT is more prone to AE compared to SLIT, overall severe reactions are rare and occur during build-up and early maintenance.

Shellfish, including various species of mollusks (e.g., mussels, clams, and oysters) and crustaceans (e.g., shrimp, prawn, lobster, and crab), have been a keystone of healthy dietary recommendations due to their valuable protein content. In parallel with their consumption, allergic reactions related to shellfish may be increasing. Adverse reactions to shellfish are classified into different groups: (1) Immunological reactions, including IgE and non-IgE allergic reactions; (2) non-immunological reactions, including toxic reactions and food intolerance. The IgE-mediated reactions occur within about two hours after ingestion of the shellfish and range from urticaria, angioedema, nausea, and vomiting to respiratory signs and symptoms such as bronchospasm, laryngeal oedema, and anaphylaxis. The most common allergenic proteins involved in IgE-mediated allergic reactions to shellfish include tropomyosin, arginine kinase, myosin light chain, sarcoplasmic calcium-binding protein, troponin c, and triosephosphate isomerase. Over the past decades, the knowledge gained on the identification of the molecular features of different shellfish allergens improved the diagnosis and the potential design of allergen immunotherapy for shellfish allergy. Unfortunately, immunotherapeutic studies and some diagnostic tools are still restricted in a research context and need to be validated before being implemented into clinical practice. However, they seem promising for improving management strategies for shellfish allergy. In this review, epidemiology, pathogenesis, clinical features, diagnosis, and management of shellfish allergies in children are presented. The cross reactivity among different forms of shellfish and immunotherapeutic approaches, including unmodified allergens, hypoallergens, peptide based, and DNA-based vaccines, are also addressed.

The post hoc analysis presented here aimed to address the influence of endogenous vitamin D in the immunological mechanism underlying effective mite allergoid immunotherapy (AIT). Previously, we have shown that in allergic children, after 12 months of this immunoactive treatment, functionally potentiated memory regulatory T cells are identified. Indeed, AIT is the only known treatment that is able to reshape the detrimental immune response against the allergen into a non-noxious one. Besides, VD is widely considered an immunoregulatory molecule that is endogenously produced and exogenously provided by foods and supplements that might interact with the AIT mechanism, thus affecting its outcome. Therefore, a post hoc analysis of the clinical and immunological data from three different cohorts of allergic patients was performed. One cohort (N = 70) was on a standard symptom-controlling pharmacological treatment, while the other to (N = 60 and N = 35) were treated with AIT for 12 months. In the first cohort, a lower mean endogenous VD level (<22 ng/mL) was observed along with worse symptoms and a greater use of medications. Remarkably, the comparison between two sub-cohorts of patients with a serum VD level above (N = 32) or below (N = 28) a cut-off value set at the mean value (27 ng/mL) revealed that optimal improvement of all clinical and immune parameters was achieved (as expected from effective AIT), irrespective of the VD level. Notably, the third analysis, carried out on one cohort of AIT patients that were also concomitantly taking VD3 as a food supplement (N = 19), was distinguished by an uppermost overall treatment outcome (the amelioration of symptoms, the lowest medication requirements, and a reduction in the total and allergen-specific IgE levels), as well as an increase in the allergen-specific tolerogenic memory T regulatory cells. These findings suggest that the endogenous VD level affects the allergy severity and allergen immunotherapy effectiveness. In addition, VD3 might be investigated as an add-on supplement to obtain the best out of immunotherapy in VD-deficient/-insufficient allergic patients. The immunogenic, but low-allergenic, mite allergoid used as the bioactive agent might have contributed to minimizing the allergic response and highlighting the immunological effects described here.

Venom immunotherapy (VIT) represents a potential therapeutic approach for the management of venom allergies, aiming to modify the immune response to venom allergens and enhance its precision. Previous studies have demonstrated that VIT induces a shift in T helper cell responses from Th2 to Th1, characterized by the production of IL-2 and interferon gamma by CD4+ and CD8+ cells. In order to explore long-term pathways following VIT treatment and verify potential new outcomes, the serum concentrations of 30 cytokines were assessed in a cohort of 61 patients (18 control, 43 study group) exhibiting hypersensitivity to wasp venom. Cytokine levels were measured at 0, 2, 6, and 24 weeks after the initiation phase of VIT in the study group. The present study found no significant alterations in the levels of IL-2 and IFN-γ in the peripheral blood following VIT. However, a noteworthy finding was the substantial increase in the concentration of IL-12, a cytokine capable of promoting the differentiation of Th0 cells into Th1 cells. This observation supports the involvement of the Th1 pathway in the desensitization process induced by VIT. Additionally, the study revealed a significant rise in the levels of IL-9 and TGF-β after VIT. These cytokines may play a role in the generation of inducible regulatory T (Treg) cells, indicating their potential importance in the immune response to venom allergens and the desensitization process associated with VIT. Nevertheless, further investigations are required to comprehend the underlying mechanisms driving the VIT process comprehensively.

To increase the prediction accuracy of positive oral food challenge (OFC) outcomes during stepwise slow oral immunotherapy (SS-OIT) in children with a hen's egg (HE) allergy, we evaluated the predictive value of the combination of antigen-specific IgE (sIgE) with antigen binding avidity and sIgG4 values. Sixty-three children with HE allergy undergoing SS-OIT were subjected to repeated OFCs with HE. We measured the ovomucoid (OVM)-sIgE by ImmunoCAP or densely carboxylated protein (DCP) microarray, sIgG4 by DCP microarray, and the binding avidity of OVM sIgE defined as the level of 1/IC50 (nM) measured by competitive binding inhibition assays. The OFC was positive in 37 (59%) patients undergoing SSOIT. Significant differences in DCP-OVM-sIgE, CAP-OVM-sIgE, I/IC50, DCP-OVM-sIgG4, the multiplication products of DCP-OVM-sIgE, and the binding avidity of DCP-OVM-sIgE (DCP-OVM-sIgE/IC50) and DCP OVM-sIgE/sIgG4 were compared between the negative and positive groups (p < 0.01). Among them, the variable with the greatest area under the receiver operating characteristic curve was DCP-OVM-sIgE/IC50 (0.84), followed by DCP-OVM-sIgE/sIgG4 (0.81). DCP-OVM-sIgE/IC50 and DCP-OVM sIgE/sIgG4 are potentially useful markers for the prediction of positive OFCs during HE-SS-OIT and may allow proper evaluation of the current allergic status in the healing process during HE-SS-OIT.

Nowadays, immunotherapy is one of the most essential treatments for various diseases and a broad spectrum of disorders are assumed to be treated by altering the function of the immune system. For this reason, immunotherapy has attracted a great deal of attention and numerous studies on different approaches for immunotherapies have been investigated, using multiple biomaterials and carriers, from nanoparticles (NPs) to microneedles (MNs). In this review, the immunotherapy strategies, biomaterials, devices, and diseases supposed to be treated by immunotherapeutic strategies are reviewed. Several transdermal therapeutic methods, including semisolids, skin patches, chemical, and physical skin penetration enhancers, are discussed. MNs are the most frequent devices implemented in transdermal immunotherapy of cancers (e.g., melanoma, squamous cell carcinoma, cervical, and breast cancer), infectious (e.g., COVID-19), allergic and autoimmune disorders (e.g., Duchenne's muscular dystrophy and Pollinosis). The biomaterials used in transdermal immunotherapy vary in shape, size, and sensitivity to external stimuli (e.g., magnetic field, photo, redox, pH, thermal, and even multi stimuli-responsive) were reported. Correspondingly, vesicle-based NPs, including niosomes, transferosomes, ethosomes, microemulsions, transfersomes, and exosomes, are also discussed. In addition, transdermal immunotherapy using vaccines has been reviewed for Ebola, Neisseria gonorrhoeae, Hepatitis B virus, Influenza virus, respiratory syncytial virus, Hand-foot-and-mouth disease, and Tetanus.

Allergic rhinitis (AR) is a widespread disease that can be associated with other conditions, including conjunctivitis, rhinosinusitis, asthma, food allergy, and atopic dermatitis. Diagnosis is based on the history and documentation of sensitization, such as the production of allergenspecific IgE, preferably using molecular diagnostics. Treatments are based on patient education, non-pharmacological and pharmacological remedies, allergen-specific immunotherapy (AIT), and surgery. Symptomatic treatments mainly concern intranasal/oral antihistamines and/or nasal corticosteroids.

This review discusses current and emerging management strategies for AR, covering pharmacological and non-pharmacological remedies, AIT, and biologics in selected cases with associated severe asthma. However, AIT presently remains the unique causal treatment for AR.

The management of allergic rhinitis could include new straegies. In this regard, particular interest should be considered in the fixed association between intranasal antihistamines and corticosteroids, probiotics and other natural substances, and new formulations (tablets) of AIT.

The efficacy of allergen immunotherapy (AIT) has been demostrated in numerous randomized clinical trials (RCT) with optimal conditions and strong evidence. In recent years, numerous real-life studies have been developed to minimize the limitations of the of RCTs (highly selected patiens, expensive, usual duration of 1-2 years and not suitable for assesing adherence and persistence), and they have provided valuable information that complements the information obtained in RCTs such as evidence of the effectiveness of AIT over an extended period of time and in a larger number of patients. To minimize limitations of this kind of studies (prone to confounding bias, generally retrospective, data sources of variable quality and study heterogeneity), some tools have been developed by both scientific and regulatory societies. Both types of studies should complement each other in order to advance the knowledge of AIT.

This review aims to present the current knowledge on the effectiveness and safety of allergen immunotherapy (AIT) in patients over 60 years of age with inhalant allergies.

Over the last 10 years, the problem of immunoglobulin E allergy in seniors has been noticed by many authors. At the same time, in the 1990s, trials of desensitization to selected inhalant allergens were started, obtaining evidence of the effectiveness of AIT, both with the use of sublingual immunotherapy (SLIT) and injection immunotherapy (SCIT), in patients over 60 years of age with allergic rhinitis. Such data have been confirmed for AITs for grasses, birch, and house dust mites. Currently, these patients are being monitored to assess the long-term effect of AIT. All available observations confirm the high safety of AIT in seniors.

Seniors with allergic rhinitis or asthma may qualify for IT if they do not have contraindications. These patients can experience a sustained clinical benefit even after completing AIT treatment. Studies indicate that injectable and sublingual routes of administration may be effective in this age group, provided the suspect allergen is accurately diagnosed.