The Minimal Clinically Important Difference in Allergen Immunotherapy: An Evidence-Based Approach.

Background: Regulatory authorities recommend a combination of symptom and medication scores during the grass pollen season as a primary endpoint for Phase III allergen immunotherapy (AIT) trials targeting allergic rhinoconjunctivitis. However, many composite primary endpoint scales exist; none are validated, nor do they have a well-justified minimal clinically important difference (MCID).

Methods: Direct patient feedback from 1071 grass-allergic patients was obtained to determine the minimally relevant improvement in allergic symptoms and translated into an MCID for the EAACI recommended CSMS.

Biomimetic Apatite Nanoparticles and Microcrystalline Tyrosine as Biocompatible Vaccine Adjuvants: Performance in a Bluetongue Virus Sheep Model.

Aluminum oxyhydroxide (AlOOH) is the most widely used vaccine adjuvant, but its known adverse effects prompt the finding of other, safer alternative adjuvants. This study compares in sheep the global performance and safety of vaccine prototypes against bluetongue virus (BTV) formulated with AlOOH, biomimetic apatite nanoparticles (ApNPs), and microcrystalline tyrosine (MCT). Five groups of 6 sheep were included in the study: control, BTV serotype 4 alone, and BTV-4 combined either with AlOOH, ApNPs, or MCT.

Modulation of Cellular, Molecular, and Humoral Responses by PQ Grass 27,600 SU for the Treatment of Seasonal Allergic Rhinitis: A Randomised Double Blind Placebo Control Exploratory Field Study.

Background: A short-course pre-seasonal subcutaneous injection of PQ Grass is clinically effective for the treatment of allergic rhinitis, though its mechanism remains unclear. The aim of the study was to interrogate immunological mechanisms induced by PQ Grass conventional and extended regimens.

Methods: A RDBPC exploratory field study involving participants that either received injections of PQ Grass with a cumulative dose of 27,600 SU conventional (six once weekly injections) or extended regimen (three once weekly injections followed by three once monthly injections) or placebo containing microcrystalline tyrosine (MCT) (placebo + MCT) or saline (placebo) was performed.

TAPAS-A Prospective, Multicentre, Long-Term Cohort Study in Children, Adolescents and Adults with Seasonal Allergic Rhinitis-Design and Early Results.

: The guideline on allergen-specific immunotherapy of the European Academy of Allergy and Clinical Immunology recommends subcutaneous allergen-specific immunotherapy for the treatment of allergic rhinitis in children and adults with moderate to severe symptoms. The five years cohort study described below was designed in 2020 to demonstrate non-inferiority in terms of safety, tolerability and efficacy in a paediatric population compared with adult patients treated with microcrystalline tyrosine-adsorbed allergoids for their tree and grass pollen allergy in a perennial setting. Here, we present the preliminary findings from the first year.

Six Injections of Modified Adjuvanted PQ Grass Is Effective and Well-Tolerated in a Pivotal Phase III Trial.

Background: PQ Grass 27600 SU (PQ Grass) cumulative dose is a pre-seasonal, six-injection, aluminium-free, modified subcutaneous immunotherapy product under development for the treatment of allergic rhinitis (AR). A pivotal Phase III randomised double-blind, placebo-controlled clinical trial was performed to evaluate the efficacy and safety of PQ Grass in subjects with seasonal AR.

Methods: An adaptive group sequential trial PQGrass306 (G306) with one pre-defined interim analysis was designed, using 2 parallel groups applying a 1:1 active versus placebo randomisation of patients aged 18-65.

Ara h 2-expressing cucumber mosaic virus-like particle (VLP Peanut) induces in vitro tolerogenic cellular responses in peanut-allergic individuals.

Background: Peanut allergy (PA) is one of the most prevalent food allergies with a lack of favorable safety/efficacy treatment. A cucumber mosaic virus-like particle expressing peanut allergen component Ara h 2 (VLP Peanut) has been developed as a novel therapeutic approach for PA.

Objective: We assessed the tolerogenic properties and reactivity of VLP Peanut.

On the role of antibody affinity and avidity in the IgE-mediated allergic response.

Type I hypersensitivity, also known as classical allergy, is mediated via allergen-specific IgE antibodies bound to type I FcR (FcεRI) on the surface of mast cells and basophils upon cross-linking by allergens. This IgE-mediated cellular activation may be blocked by allergen-specific IgG through multiple mechanisms, including direct neutralization of the allergen or engagement of the inhibitory receptor FcγRIIb which blocks IgE signal transduction. In addition, co-engagement of FcεRI and FcγRIIb by IgE-IgG-allergen immune complexes causes down regulation of receptor-bound IgE, resulting in desensitization of the cells.

Influence of antigen density and TLR ligands on preclinical efficacy of a VLP-based vaccine against peanut allergy.

Background: Virus-like particle (VLP) Peanut is a novel immunotherapeutic vaccine candidate for the treatment of peanut allergy. The active pharmaceutical ingredient represents cucumber mosaic VLPs (CuMV -VLPs) that are genetically fused with one of the major peanut allergens, Ara h 2 (CuMV -Ara h 2). We previously demonstrated the immunogenicity and the protective capacity of VLP Peanut-based immunization in a murine model for peanut allergy.

The holo beta-lactoglobulin lozenge reduces symptoms in cat allergy-Evaluation in an allergen exposure chamber and by titrated nasal allergen challenge.

Background: The allergists´ tool box in cat allergy management is limited. Clinical studies have shown that holo beta-lactoglobulin (holoBLG) can restore micronutritional deficits in atopic immune cells and alleviate allergic symptoms in a completely allergen-nonspecific manner. With this study, we aimed to provide proof of principle in cat allergy.

The next generation virus-like particle platform for the treatment of peanut allergy.

Background: Allergy to peanut is one of the leading causes of anaphylactic reactions among food allergic patients. Immunization against peanut allergy with a safe and protective vaccine holds a promise to induce durable protection against anaphylaxis caused by exposure to peanut. A novel vaccine candidate (VLP Peanut), based on virus-like particles (VLPs), is described here for the treatment of peanut allergy.

In situ delivery of nanoparticles formulated with micron-sized crystals protects from murine melanoma.

Introduction: Intratumoral injections of novel therapeutics can activate tumor antigen-specific T cells for locoregional tumor control and may even induce durable systemic protection (against distant metastases) via recirculating T cells. Here we explored the possibility of a universal immunotherapy that promotes T-cell responses in situ and beyond, upon intratumoral injection of nanoparticles formulated with micron-sized crystals.

Methods: Cucumber mosaic virus-like particles containing a tetanus toxin peptide (CuMV) were formulated with microcrystalline tyrosine (MCT) adjuvant and injected directly in B16F10 melanoma tumors.

Allergen Content of Therapeutic Preparations for Allergen-Specific Immunotherapy of European Paper Wasp Venom Allergy.

Allergy to (European paper wasp) venom is of particular relevance in Southern Europe, potentially becoming a threat in other regions in the near future, and can be effectively cured by venom immunotherapy (VIT). As allergen content in extracts may vary and have an impact on diagnostic and therapeutic approaches, the aim was to compare five therapeutic preparations for VIT of venom allergy available in Spain. Products from five different suppliers were analyzed by SDS-PAGE and LC-MS/MS and compared with a reference venom sample.

Ameliorating Atopy by Compensating Micronutritional Deficiencies in Immune Cells: A Double-Blind Placebo-Controlled Pilot Study.

Background: Functional iron deficiency facilitates allergy development and amplifies the symptom burden in people experiencing allergies. Previously we selectively delivered micronutrients to immune cells with β-lactoglobulin as carrier (holoBLG), resulting in immune resilience and allergy prevention.

Objective: The clinical efficacy of a food for special medical purposes-lozenge containing β-lactoglobulin with iron, polyphenols, retinoic acid, and zinc (holoBLG lozenge) was assessed in allergic women.

Ex Vivo Immunomodulatory Effects of Lactobacillus-, Lacticaseibacillus-, and Bifidobacterium-Containing Synbiotics on Human Peripheral Blood Mononuclear Cells and Monocyte-Derived Dendritic Cells in the Context of Grass Pollen Allergy.

Sensing of the intestinal microbiota by the host immune system is important to induce protective immune responses. Hence, modification of the gut microbiota might be able to prevent or treat allergies, mediated by proinflammatory Th2 immune responses. The aim was to investigate the ex vivo immunomodulatory effects of the synbiotics Pollagen® and Kallergen®, containing the probiotic bacterial strains Lactobacillus, Lacticaseibacillus and Bifidobacterium, in the context of grass pollen allergy.

Micronutritional supplementation with a holoBLG-based FSMP (food for special medical purposes)-lozenge alleviates allergic symptoms in BALB/c mice: Imitating the protective farm effect.

Background: Previously, the protective farm effect was imitated using the whey protein beta-lactoglobulin (BLG) that is spiked with iron-flavonoid complexes. Here, we formulated for clinical translation a lozenge as food for special medical purposes (FSMP) using catechin-iron complexes as ligands for BLG. The lozenge was tested in vitro and in a therapeutical BALB/c mice model.

Dogmas, challenges, and promises in phase III allergen immunotherapy studies.

The concept of treatment of an allergy with the offending allergen was introduced more than a century ago. Allergen immunotherapy (AIT) is the only disease modifying treatment of allergic diseases caused by inhalational allergens and insect venoms. Despite this, only few AIT products have reached licensure in the US or an official marketing authorization status in European countries.

Venom Immunotherapy: From Proteins to Product to Patient Protection.

In this review, we outline and reflect on the important differences between allergen-specific immunotherapy for inhalant allergies (i.e., aeroallergens) and venom-specific immunotherapy (VIT), with a special focus on Venomil Bee and Wasp.

Immunological effects of adjuvanted low-dose allergoid allergen-specific immunotherapy in experimental murine house dust mite allergy.

Background: Native allergen extracts or chemically modified allergoids are routinely used to induce allergen tolerance in allergen-specific immunotherapy (AIT), although mechanistic side-by-side studies are rare. It is paramount to balance optimal dose and allergenicity to achieve efficacy warranting safety. AIT safety and efficacy could be addressed by allergen dose reduction and/or use of allergoids and immunostimulatory adjuvants, respectively.

First evaluation of a symbiotic food supplement in an allergen exposure chamber in birch pollen allergic patients.

Background: Allergic rhinitis/rhinoconjunctivitis is the most common immune disease worldwide, but still largely underestimated, underdiagnosed, and undertreated. Dysbiosis and reduced microbial diversity is linked to the development of allergies, and the immunomodulatory effects of pro- and prebiotics might be used to counteract microbiome dysbiosis in allergy. Adequate symbiotic (multi-strain pro-, plus prebiotic) supplementation can be suggested as a complementary approach in the management of allergic rhinitis.

Shaping Modern Vaccines: Adjuvant Systems Using MicroCrystalline Tyrosine (MCT).

The concept of adjuvants or adjuvant systems, used in vaccines, exploit evolutionary relationships associated with how the immune system may initially respond to a foreign antigen or pathogen, thus mimicking natural exposure. This is particularly relevant during the non-specific innate stage of the immune response; as such, the quality of this response may dictate specific adaptive responses and conferred memory/protection to that specific antigen or pathogen. Therefore, adjuvants may optimise this response in the most appropriate way for a specific disease.

Vaccination against Allergy: A Paradigm Shift?

Since the discovery that IgE antibodies mediate allergy, decades of research have unraveled complex mechanisms associated with conventional immunotherapy and the vital protagonists that shape 'immune tolerance' to allergens. Debate exists on what should constitute the dominant effector mechanism in driving rational drug designs for next-generation immunotherapies. As vaccine technology continues to advance, the development of novel vaccines in this area of continued medical need might stand on a threshold of breakthrough inspired by experiments by Dunbar on the passive vaccination of allergic animals more than 100 years ago.

Correction: -Derived E-DIII Protein Displayed on Immunologically Optimized VLPs Induces Neutralizing Antibodies without Causing Enhancement of Infection. 2019, , 72.

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Vaccine against peanut allergy based on engineered virus-like particles displaying single major peanut allergens.

Background: Peanut allergy is a severe and increasingly frequent disease with high medical, psychosocial, and economic burden for affected patients and wider society. A causal, safe, and effective therapy is not yet available.

Objective: We sought to develop an immunogenic, protective, and nonreactogenic vaccine candidate against peanut allergy based on virus-like particles (VLPs) coupled to single peanut allergens.

-Derived E-DIII Protein Displayed on Immunologically Optimized VLPs Induces Neutralizing Antibodies without Causing Enhancement of Infection.

(ZIKV) is a similar to (DENV) in terms of transmission and clinical manifestations, and usually both viruses are found to co-circulate. ZIKV is usually transmitted by mosquitoes bites, but may also be transmitted by blood transfusion, via the maternal-foetal route, and sexually. After 2015, when the most extensive outbreak of ZIKV had occurred in Brazil and subsequently spread throughout the rest of South America, it became evident that ZIKV infection during the first trimester of pregnancy was associated with microcephaly and other neurological complications in newborns.