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If you are allergic to peanuts, your immune system, because of MBC2, remembers that you're allergic to peanuts, and when you encounter them again it creates more of the antibodies that make you allergic Researchers have long known that IgE antibodies, which stimulate other immune cells called mast cells and basophils, are the key players in the process that ultimately leads to allergy symptoms. However, most of the cells that produce IgE antibodies, including B cells, are relatively short-lived. A research team recently used single-cell RNA sequencing to analyze samples of immune cells taken from 58 children with peanut allergies, along with 14 non-allergic controls. This revealed MBC2s, the volume of which corresponded to higher levels of IgE in the allergic patients. Another study isolated antigen-specific memory B cells in immune cell samples taken from adult patients with the allergies, along with a group of non-allergic controls. Single-cell RNA sequencing on these cells again identified the MBC2s, and showed that patients with allergies had higher populations of them than those without. Findings therefore suggest that there are two requirements for an allergic reaction. The first is the presence of type 2 inflammation—a form of inflammation where the body sends out type 2 immune cells, like mast cells and basophils, in response to intruders—while the second is MBC2s that are specific to a particular antigen. The work therefore suggests possible avenues for treating allergies. One strategy might be to target MBC2s with biologics, the perspective authors said; a possible contender for the job might be dupilumab, brand name Dupixent, an antibody that blocks receptors found on MBC2s. Another possibility is the antibody omalizumab—Genentech and Novartis' Xolair—which prevents IgEs from binding to mast cells and basophil. Another potential therapeutic avenue would be to use allergen immunotherapy in combination with biologicals targeting [a receptor found on MBC2s] or IgE, which could further attenuate type 2 B memory cells and provide a long-term benefit. #Biotech #BioPharma #Allergy

ROXALL Research Updates at EAACI 2024   As a company with the full cycle of allergen-specific immunotherapy products, ROXALL runs extensive research to understand the nature of allergy better for the development of leading vaccines. This year, at EAACI Congress 2024, ROXALL researchers shared some of their recent results in the development of AIT to wasp venoms, house dust mites, and cat allergens.   Since 2010, the yellow-legged hornet has spread in the northern part of Spain causing multiple anaphylactic reaction in sensitised persons. Defining a specific sensitisation is an essential step to develop allergen preparations for AIT. In the study «Determination of Sensitisation Pattern in Patients with anaphylaxis to Vespa vetulina in the north of Spain», 68 patients with anaphylactic reactions after hornet stings were selected for the study. Pure venom was obtained in ROXALL laboratory in Bilbao, Spain. Specific IgE level analysis measured using ImmunoCAP 250 system demonstrated that all patients were sensitised to hornet venoms with the prevalence of Pol d 5, Ves v 5, and Ves v 1 allergen components. Immunobloting with our pure venom resulted in the positive reactions to Ves v 2, Ves v 1, and Ves v 5 allergen components. This profile helps us to understand the key allergens that should be paid the highest attention during development of new vaccines.   House dust mites are among the most important perennial allergens worldwide. In a «Clinical Evaluation of Subcutaneous Therapy (SCIT) Containing a Mixture of Mites, in Depot Polymerised Formulation, Without Dilution Effect. Results from a Prospective Multicenter Study», ROXALL studied the effect of the mixing of 2 mite allergoids without dilution in the subcutaneous immunotherapy (SCIT) formulation. After finishing 12-months SCIT treatment course, the vast majority of patients (around 97%) significantly improved their symptoms with no systemic adverse reactions. The study demonstrated the high efficacy and safety profile of the new SCIT treatment with undiluted mixed mite extracts. Developing an improved formulation for SCIT aimed to treat patients is another promising approach that can bring relief to more patients for whom a classical immunotherapy would not be helpful.   One of the most frustrating allergies is the allergy to furry animals that requires limiting contact for sensitised people. At EAACI 2024, ROXALL presented a study «Allergen-specific Immunotherapy Based on Purified and Modified Fel d 1 Allergen from Cat Dander», aimed to develop a safe and efficient AIT based on the major domestic cat allergen, Fel d 1. In the current study, Fel d 1 allergen was purified from cat dander extract with monoclonal antibodies and then modified to the form of allergoid with 1% of allergenicity. #roxall #roxallgroup #allergenimmunotherapy #allergology #eaaci #eaaci2024

#Allergen #immunotherapy (AIT) is the monitored administration of allergens at increasing doses as a treatment for IgE-mediated allergic conditions. Currently, AIT is the only disease-modifying therapy that can achieve allergen tolerance and resolve Th2-driven allergic inflammation. The transition toward tolerogenic responses requires maintaining regulatory T cells and regulatory B cells, normalizing allergen-specific T cells and B cells, shifting IgE towards IgG production, adjusting activation thresholds for mast cells and basophils, and modulating non-allergen-specific immune cells. Over time, patients undergoing allergen immunotherapy experience decreased sensitivity to allergens, resulting in a significant decrease in allergic inflammation parameters, relief of symptoms and improved quality of life. In this issue, Rodríguez del Río et al. perform a systematic review to identify outcomes related to measuring the efficacy of food allergen immunotherapy. Zemelka-Wiacek et al. provide an overview of the latest developments in allergen immunotherapy, underscoring the critical role of clinical and biomarker endpoints definition and assessment, big data management, application of artificial intelligence, new methodology in clinical trials, disease endotypes and application of biologicals, personalized approaches, and pharmacoeconomics. Wipperman et al. investigate the effects of subcutaneous immunotherapy in combination with dupilumab on gene expression in nasal tissue in the context of allergic rhinitis, seasonal allergen exposure, and nasal allergen challenge. Mösges and Zeyen et al. report the results of a first-in-human dose-finding study using mannan-conjugated birch pollen allergoids. Khaitov et al. report the preparation and characterization of a recombinant vaccine, AB-PreS, designed to confer protective immunity against birch pollen and associated food allergy. Hamelmann et al. assess the added clinical and economic benefits of early initiation of sublingual allergen immunotherapy tablets in children with allergic rhinitis. Bager et al. evaluate the effectiveness of pollen allergen immunotherapy on allergic rhinitis over 18 years in a national cohort study. Jutel et al. evaluate real-world data in a retrospective, observational cohort study to show the long-term effectiveness of house dust mite subcutaneous immunotherapy. Voskamp et al. investigate the changes in allergen-responsive B-cells after subcutaneous allergen immunotherapy. journalallergy.com

Researchers with McMaster University and Denmark-based pharmaceutical company ALK-Abello A/S have made a groundbreaking discovery: a new cell that remembers allergies. The discovery gives scientists and researchers a new target in treating allergies and could lead to new therapeutics. The research, published in Science Translational Medicine, coins the brand-new cell as a type-2 memory B cell (MBC2). "We've discovered a type of memory B cell that had unique characteristics and a unique gene signature that has not been described before," says Josh Koenig, assistant professor with McMaster's Department of Medicine and co-lead of the study. "We found allergic people had this memory B cell against their allergen, but non-allergic people had very few, if any." B cells are a type of immune cell that makes antibodies. These cells help fight off infections but can also cause allergies. "Let's say you're allergic to peanuts. Your immune system, because of MBC2, remembers that you're allergic to peanuts, and when you encounter them again, it creates more of the antibodies that make you allergic," Koenig says. To come to this discovery, researchers created tetramers—a type of fluorescent molecule—out of allergens like Birch pollen and peanuts to locate difficult-to-find memory B cells. Koenig and his team previously wrote the instruction manual on how to use tetramers to locate these elusive cells. Researchers further leveraged samples from ALK clinical trialswith tablet sublingual immunotherapy, which allows for sequencing large amounts of IgE-producing B cells. Using cutting-edge technology such as single-cell transcriptomics and deep sequencing of antibody gene repertoires on clinical trial samples, they were able to make direct connections between MBC2 and IgE, the type of antibody that triggers the allergic reaction. This provided necessary context, ultimately revealing the MBC2 as the home of allergy. Read more: https://lnkd.in/eUmmherm Stay in touch with all the leading stories by subscribing to our LinkedIn Newsletter here: https://bit.ly/3RbdKtc

IgE-Mediated Passive Cutaneous Anaphylaxis (PCA) Model Allergies are hypersensitivity disorders mediated by immunological mechanisms that result in tissue damage and are involved in many diseases such as atopic dermatitis, rhinitis, asthma, and anaphylaxis. Passive cutaneous anaphylaxis (PCA) is an animal model for inflammatory reactions in Type I allergy. Mast cells and basophils are critical for allergic disorders. These cells express surface membrane receptors with a high affinity and specificity for IgE. Activated mast cells secrete granules containing various allergic mediators such as beta-hexosaminidase, histamines, eicosanoids, and pro-inflammatory cytokines. Mechanistically, the interaction of Fc&RI with anti-bound IgE causes the activation of a signaling cascade involving phospholipase C and mitogen-activated protein kinases (MAPKs). The IgE receptor activates the JNK pathway through the MEKK2-MKK4/7 cascade; this pathway is essential for the induced expression of some cytokine genes such as IL-4, IL-6, or TNF-a and is activated following antigenic mast cell activation. These cytokine-induced reactions then cause tissue inflammation and anaphylaxis. This model is useful as a quick screen in drug testing studies to evaluate inhibition of inflammation efficacy. Reference drugs: Betamethasone cream (Topical) prednisonlone (systemic application). Please contact me : yongpingwbi@gmail.com, or 4108129723 if you would like to know more details about this model for your drug development or research.

Source: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology This study explores a method for assessing the avidity of polyclonal allergen-specific serum antibodies. The researchers used a modified ELISA protocol with monoclonal antibodies to disrupt antibody-allergen complexes and measure the residual antibodies. The results showed that the pH range used was effective in disrupting allergen complexes without compromising allergen integrity. The avidity indexes of the monoclonal antibodies correlated with their dissociation constants and were not affected by epitope specificity or the presence of serum proteins. The study concludes that acidic disruption of allergen-antibody complexes can be used to estimate the net-binding force of polyclonal serum antibodies and facilitate affinity-related research in allergen immunotherapy.

Exciting news from AstraZeneca: the two-drug inhaler Airsupra is proving to be a game-changer for asthma patients 🫁💊 Fresh results from the phase 3b BATURA trial reveal that Airsupra significantly reduces the risk of severe asthma exacerbations when used as an as-needed rescue medication, outperforming traditional albuterol inhalers. AstraZeneca is preparing to present these findings to health authorities at the upcoming American College of Allergy, Asthma, and Immunology annual meeting on October 26th. Read the full news story here >> https://lnkd.in/e2vpbAUR #NESFircroft #Pharmaceuticals #Healthcare

Over the past couple of decades a lot of great scientists have helped to improve our understanding on the molecular & cellular mechanisms underlying the pathophysiology of allergies #IgE #type2cytokines #alarmins Those discoveries have been essential to identify viable therapeutic targets and to develop effective biologicals for a variety of allergic conditions #omalizumab #dupilumab #tezepelumab As always in drug discovery there is room for improvements! The concept of targeting IgE on multiple levels of the allergic cascade has only recently been developed. This multi-level targeting approach might present a promising future strategy to rapidly and efficiently shut down allergies in a sustained manner #nextGenerationAntiIgEs #multipleModesOfAction If you want to know more, take a look at our extensive open access review article about „Therapeutic monoclonal antibodies in allergy: Targeting IgE, cytokine, and alarmin pathways“. University of Bern & Stanford University, Department for BioMedical Research DBMR, Rheumatologie_Immunologie Forschung Bern

#Allergen #immunotherapy (AIT) is a therapeutic approach that involves the controlled delivery of allergens to treat IgE-mediated allergic disorders. As patients progress through AIT, a pivotal immunological shift occurs, steering towards a state of allergen tolerance. This AIT-driven transformation results in a gradual reduction in allergen hypersensitivity, ultimately leading to the alleviation of allergic symptoms.   This issue starts with an editorial by Ng and Wang highlighting the use of mobile health apps in AIT treatment. Pfaar et al., in anEAACI Position Paper, examine the potential, limitations, and future developments of mHealth solutions for digitally-enabled person-centered care in allergen immunotherapy, while suggesting optimal tools for clinical and scientific applications. Dwivedi et al., in their comprehensive review, assess the efficacy, safety, and immunomodulatory effects of preventive allergen immunotherapy in children, highlighting promising results in preventing disease progression from allergic rhinitis/conjunctivitis to asthma. Spiric et al. discuss the quality control of allergen products by mass spectrometry, within the EU regulatory framework. Riggioni et al., in their systematic review and meta-analyses, evaluate the efficacy and safety of immunotherapy and biologics in the management of IgE-mediated food allergy. Eguiluz-Gracia and Parkin et al. investigate the capacity of subcutaneous allergen immunotherapy to induce local and systemic blocking antibodies in patients with local allergic rhinitis. Flory and Hviid-Vyff et al. provide a critical appraisal of the intralymphatic immunotherapy method and offer pragmatic recommendations for lymph node selection and improved injections. Winther et al. compare the clinical efficacy of grass pollen subcutaneous immunotherapy and sublingual immunotherapy by evaluating seasonal symptom burden as measured by the visual analogue scale. Tontini et al. discuss the post-desensitization and post-anaphylaxis differences in mast cell activation. journalallergy.com

During times when access to care can be a challenge for patients it is important as a pharmacy team to do our part to ensure what is in our control is not a barrier. Excited to share this work I completed in collaboration with my colleagues at Yale University and Vanderbilt University to address drug allergy in a patient looking to continue therapy with leuprolide acetate. We developed a novel approach to drug desensitization and successful reintroduction of therapy! https://lnkd.in/ecw52gBX