A new immunotherapeutic approach to restore the main characteristics of cat allergies

Researchers at the Department of Infectious Immunology at the Luxembourg Institute of Health (LIH) have found that high doses of certain adjuvant molecules, namely CpG oligonucleotides, help regulate the immune system’s allergic response to the major cat allergen Feld 1. Advocated the possibility of. , Thereby inducing a tolerance-promoting reaction and restoring the main characteristics of cat allergies.

Researchers have analyzed the molecular mechanisms underlying this resistance and have proposed preclinical allergen-specific immunotherapy approaches to improve the treatment and control of this common type of allergy. The complete research results were recently published in a well-known international journal. Allergies, The official journal of the European Academy of Allergology (EAACI) and one of the world’s top two journals in the field of allergies.

Cat allergies are a rapidly increasing phenomenon characterized by hypersensitivity and excessive immune response to certain cat-related allergens, especially Fel d 1, a protein commonly found in saliva, glands, skin and fur. Symptoms of cat allergies range from mild to severe symptoms such as rhinitis and asthma, which can have fatal consequences. Drug therapy is a milder form of the option, but in more advanced cases, only allergen-specific immunotherapy (AIT) can guarantee effective and long-term treatment.

AIT usually consists of a gradual increase in the amount of the allergen in question and a subcutaneous injection until it reaches a critical dose that induces long-term immune tolerance. Nevertheless, the cat’s AIT needs to be improved. Effectiveness And safety. Researchers have optimized the T and B cell responses of the immune system through an immune adjuvant to induce the production of antibodies to Fel d 1 while minimizing the inflammatory response, thereby immunotolerance to this allergen. It was assumed that the most effective cat AIT could be achieved by increasing. ..

“We sought a new way to increase the anti-inflammatory activity of AIT using the known immunomodulatory adjuvant CpG, but at a safer dose than previously used for this type of treatment,” he said. Dr. Kathy Leonard, an allergy and clinical scientist, explains. The Immunology Research Group of the Faculty of Infectious Immunology, LIH, corresponds to the first author of the publication.

To study the cellular and clinical effects of AIT based on injections of the Fel d 1 allergen and high-dose CpG adjuvant, the team challenged Fel d1-allergic mice both in the presence and absence of the allergen. AIT.

Scientists say that AIT-treated allergic mice show significantly improved lung resistance compared to untreated allergic mice, as well as non-allergic control mice, with significant signs of airway inflammation and hypersensitivity reactions. It was observed that it decreased to. In fact, looking at Fel d 1 specific antibodies, the team found that AIT-treated allergic mice had low levels of IgE that are generally associated with allergic reactions and high levels of IgA that may have anti-inflammatory effects. And noticed that it showed IgG. Property.

In addition, AIT-treated allergic mice showed reduced levels of certain allergenic cytokine molecules produced by type 2 helpers. T cells (Th2), compared with untreated allergic animals. Researchers also found that immediately after AIT injection, the tissue of AIT-treated mice increased due to the abundance of immune cell types involved in the regulation and resistance of allergies, namely plasmacytoid dendritic cells (pDC), natural killer. I also noticed. Cells (NK), regulatory T cells (T-reg) and regulatory B cells (B-reg). These cells express high levels of tumor necrosis factor α (TNF-α) receptor 2 (TNFR-2), and NK cells also have TNF-α cytokines, which are known to play a role in suppressing allergens. It turned out to produce. A specific immune response, thereby allowing these regulatory cells to act as a “brake” for the immune system.

“At a later stage, a clear increase in TNF-α in the lungs was observed. Interestingly, AIT is a new and unique type known as biTregs that is better suited to balance allergies and inflammation. It also triggered the appearance of Tregs. antigen“Dr. Leonardo adds.

Taken together, these findings demonstrate potent anti-inflammatory and anti-allergic effects evoked by AIT with high-dose, safe-dose CpG adjuvants. But, very surprisingly, researchers have found that the underlying mechanism of this allergic protective effect has never been previously exposed to the Fel d 1 antigen and is therefore an existing allergic condition, or Under an already established allergic condition, as in the case of AIT. Elucidation of these alternative pathways opens new insights for future designs of prophylactic and curative allergic vaccines using CpG adjuvants.

Going further by translating these findings into preclinical applications, scientists have moved to a subcutaneous injection-based delivery system for Fel d 1 / CpG therapy, as opposed to the more invasive intraperitoneal route of administration. Developed. The results showed an equal reversal of all allergic characteristics, confirming the anti-allergic effect of AIT.

In essence, it proposes a preclinical model of AIT for cat allergies. It mimics the requirements for human AIT clinical trials and is already optimized for future use in translation studies. Indeed, some of our studies have included the use of endotoxin-free Feld1 allergens, which are essential in clinical practice, to prevent the development of collateral inflammatory reactions that may impair the desired induction of tolerance-promoting mechanisms. It shows novelty.

In addition, the use of the maximum dose of CpG allowed in humans has the ability to regulate established medically allergic reactions with a highly favorable safety profile when combined with the Fel d 1 allergen. Will be shown for the first time. Approved delivery mode. Based on our data, CpG is worth rethinking as an effective AIT adjuvant in humans, and we believe our research lays the foundation for the development of new and successful immunotherapeutic therapies for allergies. “

Professor Markus Ollert, Dean of LIH Infectious Immunology, Senior Author

Survey results published in international journal Allergies“Comprehensive mapping of immune tolerance results in a regulatory TNF receptor 2 signature in a mouse model of successful Feld1-specific immunotherapy using high-dose CpG adjuvants,” with the full title.