Polymerised mite allergoids with glutaraldehyde reduce proteolytic activity and enhance the stability of allergen mixtures: a proof of concept with grass mixtures

Frontiers in Allergy, Journal Year: 2025, Volume and Issue: 6

Published: Feb. 25, 2025

Polysensitized patients require allergen immunotherapy (AIT) targeting multiple allergens. However, combining extracts can lead to instability and reduced efficacy particularly due the high proteolytic activity of house dust mite (HDM) While is known that glutaraldehyde cross-linking may reduce enzymatic activity, its ability stabilize multi-allergen formulations protect key allergens from degradation remains unexplored. To evaluate impact polymerization on stability immunogenicity HDM grass pollen formulations, addressing challenges in vaccines. Stability was assessed over 24 months through protein quantification antigenic assays. Proteolytic HDM-containing measured using Azocoll, peptide substrate-based Grass evaluated by SDS-PAGE, immunoblotting, ELISA Immunogenicity mice immunized with allergoids alone or combination glutaraldehyde-polymerised HDM, measuring IgG responses, splenocyte proliferation, IL-10 production. Glutaraldehyde significantly (p < 0.0001), achieving reductions 97.7%, 77.9%, 89.9% total protease cysteine serine respectively. This inhibition protected when mixed degradation, ensuring consistent content months. Mice combined polymerised showed similar responses T-cell activation, indicating no compromise immune response allergens, secretion confirming preserved regulatory responses. Polymerised address offering stable, immunogenic vaccines maintain provide a reliable treatment option for polyallergic patients.

Language: Английский

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T Cell Exhaustion in Allergic Diseases and Allergen Immunotherapy: A Novel Biomarker?

Current Allergy and Asthma Reports, Journal Year: 2025, Volume and Issue: 25(1)

Published: March 17, 2025

Language: Английский

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Is allergen immunotherapy a model of personalized treatment in pediatric respiratory allergy?

Current Opinion in Allergy and Clinical Immunology, Journal Year: 2024, Volume and Issue: 24(2), P. 88 - 93

Published: Feb. 12, 2024

Purpose of review To recent evidence on allergen immunotherapy (AIT) as a model personalized medicine in the treatment children and adolescents with respiratory allergies. Recent findings Meta-analysis systematic studies continue to point out that AIT is an effective for Molecular allergy allows understanding patient sensitization profiles frequently change prescription AIT. There still lack showing this associated better clinical outcomes. The nasal challenge has extended indications new group subjects local allergic rhinitis. Patient selection allergens involved increasingly composition extracts be used characterizes it medicine. Summary Despite numerous carried identify best biomarker evaluate response AIT, there much disagreement, assessment (symptoms, quality life, among others) continues way therapeutic success

Language: Английский

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Allergen Immunotherapy for the Prevention and Treatment of Asthma

Clinical & Experimental Allergy, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 4, 2024

Allergic asthma is the predominant phenotype among asthmatics. Although conventional pharmacotherapy a central component in management of asthma, it does not enable control symptoms all patients. In recent decades, some uncontrolled asthmatic patients, especially those with allergic have benefited from biological therapies. However, biologics do address unmet needs left by pharmacotherapy. Furthermore, noteworthy that neither nor therapies disease-modifying properties. this context, allergen immunotherapy (AIT) represents an indispensable therapeutic arsenal against due to its immunological effects. review article, funded AIT manufacturer, we find clinical trials support as only treatment option able both improve and prevent onset worsening condition. For patients severe or other safety concerns, combination offers very promising new modalities for asthma. Trial Registration: clinicaltrials.gov identifier: NCT06027073.

Language: Английский

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Novel Approaches to Allergen Immunotherapy for Respiratory Allergies

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(11), P. 1510 - 1510

Published: Nov. 9, 2024

Allergen immunotherapy (AIT) remains the cornerstone for managing respiratory allergies, offering long-term symptom relief, disease modification, and prevention of progression. While novel approaches like intralymphatic epicutaneous combination allergens with adjuvants show promise, traditional methods remain effective safe. Hypoallergenic T-cell peptide vaccines recombinant require further research to confirm their clinical benefits. Passive immunotherapy, while demonstrating effectiveness in specific cases, needs exploration its efficacy broader applicability. Combining AIT biologics may enhance safety treatment outcomes. Despite emerging innovations, allergen-specific natural allergen extracts primary disease-modifying treatment, relief Continued is essential refine optimize strategies, providing patients more personalized options.

Language: Английский

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Mechanisms of allergen-specific immunotherapy

Folia Pharmacologica Japonica, Journal Year: 2024, Volume and Issue: 160(1), P. 43 - 47

Published: Dec. 31, 2024

Allergen-specific immunotherapy (AIT) has been a longstanding treatment for allergic diseases. Historically, subcutaneous was the main approach, but with development of sublingual preparations, which are associated fewer systemic side effects, is gaining global popularity. In Japan, approval standardized preparations in 2014 significantly accelerated its adoption. The mechanism inflammation divided into sensitization and elicitation phases. phase involves production antigen-specific IgE antibodies against particular antigen. These bind to FcεRI on mast cells basophils, preparing body an response. occurs when body, already primed these antibodies, re-exposed same antigen, triggering symptoms. This includes mechanisms where IgE-mediated cell activation leads degranulation local Th2 induces inflammation. While AIT not fully understood, they categorized desensitization immune tolerance. Desensitization induced by reducing responsiveness basophils Immune tolerance IgG4 that compete antigen binding, induction regulatory T other anti-inflammatory producing cytokines such as IL-10. still faces challenges, lack predictive biomarkers efficacy. Recent studies indicate HLA genotypes influence responsiveness. Advances genetic single-cell analysis expected address paving way improved outcomes.

Language: Английский

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Single-Domain Antibodies—Novel Tools to Study and Treat Allergies

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(14), P. 7602 - 7602

Published: July 11, 2024

IgE-mediated allergies represent a major health problem in the modern world. Apart from allergen-specific immunotherapy (AIT), only disease-modifying treatment, researchers focus on biologics that target different key molecules such as allergens, IgE, or type 2 cytokines to ameliorate allergic symptoms. Single-domain antibodies, nanobodies, are newcomers biotherapeutics, and their huge potential is being investigated various research fields since discovery 30 years ago. While they dominantly applied for theranostics of cancer treatment infectious diseases, nanobodies have become increasingly substantial allergology over last decade. In this review, we discuss prerequisites consider be important generating useful nanobody-based drug candidates treating allergies. We further summarize available data used allergen monitoring detection probes therapeutic approaches. reflect limitations addressed during development process, vivo half-life immunogenicity. Finally, speculate about novel application formats allergy might future.

Language: Английский

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Allergen-specific immunotherapy at the extremes of age: below 5 years and elderly: evidence beyond indications?

Current Opinion in Allergy and Clinical Immunology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 20, 2024

Purpose of review Allergen-specific immunotherapy (AIT) has been used in clinical practice to treat allergic diseases for over 100 years. The effectiveness and safety AIT have substantiated numerous studies; however, children before 5 years age elderly are not encompassed generally. This aims present the current understanding extremes age. Recent findings Early allergen during infancy or early childhood may prevent development sensitization common allergens, thereby reducing risk developing later life. In elderly, improved symptoms quality life reduced dependence on medication indicated importance implementation AIT. Both immunological parameters demonstrated that treatment was effective at time cessation trend sustained tolerance. Summary There is no specific lower upper limit initiating immunotherapy; it important thoroughly evaluate severity disease risks benefits each case.

Language: Английский

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Preclinical development of virus‐like particle (VLP)‐based immunotherapy against HDM allergy

Allergy, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 25, 2024

The unique disease-modifying treatment for house dust mite (HDM)-induced allergic rhinitis or asthma consists in allergen-specific immunotherapy (AIT) through sublingual subcutaneous administrations of allergen extracts. mechanisms by which AIT dampens Th2-biased HDM response leading to immune tolerance include the generation T/B regulatory Th1 cells and IgG1/IgG4 blocking antibodies.1 AP205 bacteriophage-derived virus-like particles (VLPs) displaying major allergens Der p 1 (VLP-ProDer 1, VLP-PD1N) 2 (VLP-D2) are highly hypoallergenic, promote Th1-biased responses elicit high levels specific IgG.2, 3 Such chimeric VLPs represent promising candidates design shorter, safer, more effective AIT. Using a pre-established adjuvant-free mouse model HDM-induced airway inflammation,4 we assessed therapeutic capacities bivalent vaccine VLP-PD1N/VLP-D2 (Figure 1A). BALB/c mice were intranasally sensitized challenged with Sensitized animals intramuscularly vaccinated (VLP-PD1N/VLP-D2, 5 μg/5 μg 20 μL Phosphate-buffered saline-PBS). This dose was selected according our previous immunogenicity studies.2, As controls, undecorated SpyCatcher-VLP (SC-VLP, 10 μg) PBS (allergic group). expected, typical markers inflammation evidenced mice: large influx inflammatory bronchoalveolar fluids (BALF), accumulation pulmonary eosinophils 1B), peribronchiolar/ perivascular induction mucus-producing lung tissues 1C), IL-5 BALF 1D). Remarkably, all these key parameters HDM-specific significantly similarly dampened non-specific VLP treatments 1B–D). Moreover, IFNγ detected BALFs from VLP-treated We observed significant positive inverse correlation between number respectively S1). In supernatants restimulated splenocytes, measured group equally blunted control VLP-AIT which, turn, triggered increase 2A). Treatment VLP-PD1N/D2 elicited higher production than SC-VLP. 1-/Der 2-specific IgE antibody at post-AIT time point same vaccinations VLPs. robust downregulation persisted after intranasal challenges 2B). Contrary SC-VLP, development IgG1/IgG2a titers 2C). Our results highlighted that VLP-based alleviate (lung eosinophilia/mucus-producing cells) but also Th2 cytokine as well serum levels. present animal model, is independent on potent IgG responses, mediated only vaccine. Although antibodies represents one main hallmarks successful AIT, its clinical outcomes remains debatable.5 However, persistence years inhibitory activity following discontinuation involved long-term tolerance.6 Consequently, remain be tested prolonged models confirm efficacy absence responses. hypothesize anti-allergic effects shared SC-VLP dependent TLR3/TLR7-specific innate signalling prokaryotic RNA cargo encapsulated into VLPs.3 Of note, several preclinical/clinical studies effectiveness including TLR9 (CpG motifs alone (QbG10)) TLR7 (Resiquimod) ligand7 mRNA formulated LNPs.4 could trigger brakes least interstitial macrophages expressing level.8 These restore homeostasis. Alternatively, induce trained immunity reprograming monocytes/ Type conventional dendritic (cDC2) tolerogenic depending metabolic epigenetic rewiring.9 Upcoming required elucidate extensively mechanism modulation AP205-based context allergy. contribution must particularly investigated RNAse pretreatment and/or use TLR7-deficient mice. Important still unresolved points addressed translation approach finding optimal dose, route administration confirming dispensability additional adjuvants. Further large-scale controlled will necessary evidence safety, duration protective effects. Particularly, significance VLP-specific B cell investigated. interaction antigen-presenting T deserves full attention. For human trials, produced under GMP (Good Manufacturing Procedures) conditions consistent amounts preparations secured. A.J., L.F. F.B. designed study; P.P. prepared different VLPs; S.C., C.T. T.K. performed experiments immunotherapy. A.J. provided supervision analyzed data. drafted manuscript. All authors contributed approved final version work partly funded Thailand Science Research Innovation (TSRI) Fund Chulalongkorn University (HEA663000026), 90th Anniversary Ratchadaphiseksomphot Fund. warmly thank Prof. Adam F. Sander (University Copenhagen, Denmark) providing genetic construction production. other declare they have no conflict interest. data support findings this study available corresponding author upon reasonable request. Appendix S1. Please note: publisher not responsible content functionality any supporting information supplied authors. Any queries (other missing content) should directed article.

Language: Английский

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Enhanced benefit from house dust mite immunotherapy in subjects with low serum levels of LILRA5 or CCL25

Allergy, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 9, 2024

Allergen immunotherapy (AIT) is recognized as an etiologic treatment of allergy with long-lasting effects.1 Although AIT has been associated changes in cellular and humoral parameters (e.g. ILC2, Th2A, Treg, IgE, IgG4 IgA), no predictive or follow-up marker efficacy validated today.2-4 The aim the present study was to identify, using OLINK® proximity extension assay, markers serum house dust mite allergic subjects having completed a phase 3 clinical trial evaluating sublingual tablets.5 Briefly, sub-cohort 176 participants received 300 IR tablet daily, mono polysensitised, without concomitant asthma exhibited either high low improvement selected. Serum levels at baseline 543 proteins were analysed Target 96 panels (Supplementary Material Methods, Table S1 Figure S1). When considering whole dataset correcting for multiple comparisons, Leukocyte Immunoglobulin-Like Receptor A5 (LILRA5) C-C motif chemokine ligand 25 (CCL25) found display statistically significant different (adjusted p < .05) compared responders. Focusing on individually, both confirmed have highly significantly (p .001) lower responders despite overlap between two populations (Figures 1A 2A). In order confirm results obtained OLINK®, we enquire about alternative assays allowing absolute quantification. No suitable method LILRA5. However, able perform confirmatory analyses CCL25 specific Luminex® assay mean amounts be good correlation datasets (Spearman's ρ = 0.64, (Figure S2). We further expression LILRA5 taking into consideration sensitisation status (mono- polysensitisation), combination thereof performed complementary receiver operating characteristic (ROC) 1 2). that differential polysensitised ROC large increase area under curve from 0.66 0.85 1E–H) more limited one 0.65 0.70 2E–H), thus reflecting better discriminating performances when other co-morbidities account larger effect size S3). Both reported play role inflammation-related diseases,6-8 including asthma. Specifically, expressed various immune cells, monocytes, macrophages, neutrophils B-lymphocytes.6 Cross-linking peripheral blood monocytes (PBMCs) induces production pro-inflammatory cytokines, IL-1β, TNF-α, IL-6, suggesting plays inflammation. Two soluble forms also described.6 it unclear whether they exhibit similar functions could act regulators effector responses such inhibition LILR/HLA-class I complexes.9 On hand, vivo murine vitro human studies highlighted its receptor, CCR9, are key drivers airway Particularly, CCR9+ cells CCR9+CD4+ T frequent PBMCs patients perennial conjunctivitis than healthy controls.10 context rhinitis, polysensitisation likely inflammatory patients. trend AIT-responsive may reflect less favorable system reorientation. To our knowledge, this first report potential large-scale multiplex analyses. Some limitations related number analysed, notably subgoups, should however noted. Confirmatory prospective cohorts conducted validate utility practice. future, clusterisation will help unravel patients' response profiles address needs personalized regimen. V.B.-L.F. L.M. designed research. L.M., C.A. supervised A.H. experiments. S.L. D.Y. data. wrote paper. reviewed This work financed by Stallergenes Greer. Co-authors (V.B.-L.F., S.L.) employees reports grants contracts Swiss National Science Foundation, EU CURE SynAir-G, Novartis Research Institutes, Stanford University consulting fees Sanofi/Regeneron, Sean Parker Asthma Allergy Center, Novartis, GlaxoSmithKline, Bristol-Myers Squibb SciBase. data support findings available corresponding author upon reasonable request. Data S1. Please note: publisher not responsible content functionality any supporting information supplied authors. Any queries (other missing content) directed article.

Language: Английский

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