Mepolizumab and omalizumab induce a distinct clinical effect. Mepolizumab and omalizumab induce both common and treatment-specific metabolic and protein profiles over time in patients with severe asthma. Multiomic integration and receiver operating characteristic curve analyses reveal a specific set of biomolecules suggesting their value as potential biomarkers for mepolizumab treatment. CCL11, C-C motif chemokine 11; TNFSF10, superfamily member 10.Abbreviations: CCL11, C-C motif chemokine 11; ROC, receiver operating characteristic; TNFSF10, superfamily member 10.

We used a pediatric epigenetic clock to assess epigenetic age in children from a German birth cohort. Accelerated epigenetic aging was found to be related to the presence of allergic diseases like asthma, rhinitis, or eczema, but not to non-symptomatic aeroallergen sensitization. This was supported by an epigenetic age acceleration gradient in response to allergic disease persistence and allergic multimorbidity. BAMSE, Swedish abbreviation for Children, Allergy, Milieu, Stockholm, Epidemiology; KORA F4, German population-based Cooperative Health Research in the Region of Augsburg; LISA, Life-style factors on the Development of the Immune System and Allergies in East and West Germany.

We performed guided multi-domain clustering of symptoms and triggers in school-age children across three birth cohorts. Using 15 variables, five clusters were identified. Two clusters showed a high prevalence of asthma with persistent symptoms. Questions on shortness of breath and chest tightness upon awakening were key to identifying ‘post-bronchiolitis resolving asthma’. ASHFORD, birth cohort study established in 1991 in Ashford, UK; LRTIs, lower respiratory tract infections; MAAS, Manchester Asthma and Allergy Study; SEATON, The Study of Eczema and Asthma to Observe the influence of Nutrition.

IgE binding to Juniperus ashei allergens is mediated by N-glycans different from classic CCDs. N-glycan from J. ashei pollen triggers basophil activation. GnGnXF3 is the most abundant glycan in J. ashei extract and contains a novel IgE glycotope. Abbreviations: CCD, cross-reactive carbohydrate determinant; GlcNAc, N-acetylglucosamine; GnGnXF3, biantennary N-glycan with terminal; GlcNAc, β-1,2 xylose and core α-1,3 fucose; IgE, immunoglobulin E; WB, Western blot.

Different functions of an allergy app were tested for clinical benefit in a randomized, controlled trial in patients with grass pollen allergy. Participants with pollen forecast function took more medication and had fewer symptoms than participants without pollen forecast. A symptom forecast was developed based on the study data.

In a mouse model of allergic contact dermatitis, sensitization with DNFB increased numbers of CD8⁺ T_RM cells and expression of IFN-γ with prolonged downregulation of KRT5 and KRT14 in the epidermis. Depletion of CD8⁺ T cells prevented this effect. In keratinocytes, IFN-γ and DNBS synergistically down-regulated the expression of KRT5 and KRT14. CD8⁺ T_RM, epidermal-resident memory CD8⁺ T cell; Cldn1, claudin 1; DNBS, 2,4-dinitrobenzene sulfonic acid; DNFB, 1-fluoro 2,4-dinitrobenzene; Flg, filaggrin; Ifng/IFN-γ, interferon γ; Krt/KRT, keratin; Lama5, laminin subunit alpha-5; Tmem79, transmembrane protein 79

A pivotal Phase III DBPC adaptive trial was conducted with PQ Grass 27600 SU. The primary endpoint EAACI-CSMS_0–6 demonstrated a highly significant, clinically meaningful improvement for PQ Grass of −0.27 points (95% CI: −0.42 to −0.12), corresponding to a relative difference of −20.3% (p = 0.0005) over placebo. Highly consistent secondary endpoints and a supportive safety profile were confirmed. CSMS, combined symptom and medication score; DBPC, double-blind, placebo-controlled; EAACI, European Academy of Allergy and Clinical Immunology; GPS, grass pollen season; IgG4, immunoglobulin G4; PQ Grass, Grass MATA MPL or PQ Grass 27600 SU; RQLQ[S], rhinoconjunctivitis quality of life questionnaire standardised; SCIT, subcutaneous immunotherapy; SU, standardised unit.

• We investigated the mechanisms by which a previously established VLP-based anti-IgE vaccine protects against allergic anaphylaxis.
• We show that passively administered vaccine-induced IgGs into allergic mice protects them from anaphylaxis without side effects.
• In mast cells, the IgGs prevent free IgE binding to FcεRI but fail to bind and activate FcεRI-displayed IgE.

An assay was developed to measure the allergoid content in adjuvanted grass allergoid AIT drug product (AIT-DPs) at the finished product level. Both polyclonal rabbit sera or a mouse anti-Phl p 5 mAb can be used, allowing differential product analysis. All four tested grass pollen AIT-DPs of different manufacturers could be quantified using a defined reference, demonstrating broad applicability of the assay. ACA, allergoid content assay; AIT, allergen immunotherapy; AIT-DP, adjuvanted allergoid AIT drug product; Al(OH)₃, aluminum hydroxide; FITC, fluorescein isothiocyanate; mAb, monoclonal antibody; Phl p 5, Group 5 allergen Phleum pratense; RAC, relative allergoid content.

A 6-month randomized, double-blind, placebo-controlled first-in-human clinical trial was conducted in birch pollen allergic patients comparing the Bet v 1-fold-variant BM41 with a licensed birch pollen extract-based treatment, as active comparator, and placebo. Despite SPT-confirmed hypo-allergenicity (~50% compared to natural Bet v 1), more adverse events occurred in response to BM41. In BPE-AC, the sIgG4/sIgG1 ratio tripled over time whereas for BM41 it stagnated. BM41 induced efficient serum inhibitory activity for sIgE compared to placebo but was 12-32% less efficient than BPE-AC.

Abbreviations: AIT, allergen immunotherapy; BM41, Bet v 1-fold-variant; BPE-AC, birch pollen extract-based active comparator; sIg, specific immunoglobulin; SPT, skin prick test.

siR-7-EM/KK-46 (MIR 19) is a siRNA-based anti-SARS-CoV-2 antiviral targeting viral RdRp. In adult outpatients with mild COVID-19, inhaled 5.55 mg/day of MIR 19 reduces the risk of developing moderate/severe COVID-19 by more than 50% as compared to standard therapy. MIR 19 is effective and well tolerated in non-hospitalized adult patients (18–65 years old). COVID-19, coronavirus disease 2019; RdRp, RNA-dependent RNA polymerase; RISK, the RNA-induced silencing complex; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; siRNA, short interfering RNA.