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#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

In early June 2024, our portfolio company, Allergy Therapeutics, provided further detail from positive top line results from G306 Phase III field trial to evaluate efficacy and safety of Grass MATA MPL. The trial successfully met its primary endpoint. The full results, including secondary and exploratory endpoints were presented in the European Academy of Allergy and Clinical Immunology - EAACI in June 2024. The company is now progressing towards a swift submission for the Marketing Authorisation Application for its #Grass MATA MPL immunotherapy. Positive discussions with the Paul Ehrlich Institut and the inclusion of US patients in future studies support their strategy for a Biologics License Application in the United States. CEO Manuel Llobet is optimistic about the transformative potential of the #vaccine for allergy sufferers worldwide. For more information on the research read the full press release here: https://lnkd.in/dRwv6D2y If you have any questions on this or any of our other Portfolio companies, please do not hesitate to contact us. #EAACI Conference 2024 #G306 Phase III field trial #2024Q4 #GrassAllergy #AllergyTherapeutics #Vaccine #License

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

Inimmune publishes positive proof of mechanism for TLR4 Agonist INI-2004 in Allergic Rhinitis Missoula, MT, July 30, 2024 Inimmune, a leading biotech company focused on the development of novel immunotherapies and vaccine adjuvants announced the publication of pre-clinical efficacy and safety data for INI-2004. “Intranasal administration of a synthetic TLR4 agonist INI-2004 significantly reduces allergy symptoms following therapeutic administration in a murine model of allergic sensitization” in Frontiers in Immunology on July 23, 2024 (https://lnkd.in/etGpSTiM). This research highlights the significant disease modifying impacts of INI-2004 in allergic disease following intranasal administration and describes the remarkable safety profile of this innovative treatment. INI-2004 is a fully synthetic allergen-agnostic immunotherapy that binds and activates TLR4. In a murine model of allergic rhinitis (AR), the disease modifying effect of intranasally administered INI-2004 was measured by a significant reduction in airway resistance, eosinophil influx, and cytokines involved in the pathogenesis of allergic rhinitis AR. These IND-enabling studies formed the basis for a recently completed Phase 1a/b clinical trial (NCT06038279) demonstrating that INI-2004 is safe and well tolerated over multiple administrations and improves nasal congestion in people suffering with allergic rhinits. This data demonstrates the utility of the mouse allergy model in evaluating TLR4 agonists as immunomodulatory drugs and proof of principle for the efficacy of INI-2004. Allergic rhinitis impacts over 400 million people globally and is one of the most common chronic diseases in the United States impacting 10-30% of adults and 40% of children. Safe and effective disease modifying treatments are still needed for allergic illness. “Treating the underlying disease is a critical step in stopping progression of atopy, especially for people who are poly-sensitized to multiple allergens. Inimmune is excited about this disease modifying novel treatment option for allergic rhinitis,” said Inimmune’s Chief Scientific and Strategy Officer, Dr. Jay Evans. About Inimmune Corporation Inimmune Corp. (Missoula, MT) is a privately held biotechnology company focused on the discovery and development of innovative immunotherapeutics, adjuvants, and vaccines. Inimmune is harnessing the human immune system to create safe and effective treatments for allergy, infectious disease, autoimmunity and cancer. Their laboratories and offices are housed in the Montana Technology Enterprise Center (MonTEC) in Missoula, MT (USA). For more information on Inimmune’s research and development of novel immunotherapies, vaccine adjuvants, and delivery systems, please visit www.inimmune.com. Contact: Media Relations Inimmune Corporation Phone: (406)-541-5913 Email: [email protected]

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 : [email protected], or 4108129723 if you would like to know more details about this model for your drug development or research.

Here's a new review article on some of the #immune modulatory properties of probiotics that can be used to potentially improve #vaccine efficacy. The article briefly reviews how probiotics interact with the #microbiome and the immune system as well as how probiotics might reduce dysbiosis. Immunogenic effects of probiotics on aspects of innate and acquired immunity are reviewed. The article also provides a review of some of the #antiinflammatory properties of probiotics. From a vaccine perspective, adjuvant properties of some probiotics are summarized. In addition, the use of probiotics in the areas of allergy mitigation and cancer vaccines is also covered. #probiotics #animalhealth https://lnkd.in/gk4A6EAS

Immunoglobulin E (IgE) is a key driver of type 1 hypersensitivity reactions and allergic disorders, which are globally increasing in number and severity. Although eliminating pathogenic IgE may be a powerful way to treat allergy, no therapeutic strategy reported to date can fully ablate IgE production. Interleukin-4 receptor α (IL-4Rα) signaling is required for IgE class switching, and IL-4Rα blockade gradually reduces, but does not eliminate, IgE. The persistence of IgE after IL-4Rα blockade may be due to long-lived IgE plasma cells that maintain serological memory to allergens and thus may be susceptible to plasma cell–targeted therapeutics. We demonstrate that transient administration of a B cell maturation antigen x CD3 (BCMAxCD3) #bispecific antibody markedly depletes IgE, as well as other immunoglobulins, by ablating long-lived plasma cells, although IgE and other immunoglobulins rapidly rebound after treatment. Concomitant IL-4Rα blockade specifically and durably prevents the reemergence of IgE by blocking IgE class switching while allowing the restoration of other immunoglobulins. Moreover, this combination treatment prevented anaphylaxis in mice. Together with additional cynomolgus monkey and human data, our studies demonstrate that allergic memory is primarily maintained by both non-IgE memory B cells that require class switching and long-lived IgE plasma cells. Our combination approach to durably eliminate pathogenic IgE has potential to benefit allergy in humans while preserving antibody-mediated immunity

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

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.