Researchers claim that allergen-specific immunotherapy based on high levels of adjuvant has been shown to reduce the main symptoms of cat allergy by increasing tolerance to the feline associated allergen Fel d 1, providing a promising treatment option for use in clinical trials.
Allergy to cats is a rapidly increasing phenomenon characterized by hypersensitivity and an excessive immune response to certain allergens associated with felines, in particular Fel d 1, a protein present in their saliva, on their skin and on their hair. Manifestations of this allergy can lead to the development of serious conditions such as rhinitis and asthma, with potentially fatal outcomes. Only specific immunotherapy or desensitization can ensure effective and lasting treatment in the most severe cases: repeated amounts of allergen are administered to induce clinical and immunological tolerance to the allergen.
Concretely, this process generally consists of subcutaneous injection of increasing amounts of the allergen in question, until a useful dose is reached that induces long-term immune tolerance. Nevertheless, specific immunotherapy aimed at cat allergy still requires some improvements, especially in terms of efficacy and safety. Researchers at the Luxembourg Institute of Health have hypothesized that a more effective immunotherapy could be obtained by optimizing the immune response to induce the production of antibodies against Fel d 1 while minimizing inflammation, thus increasing immune tolerance to this allergen.
The body is better protected from inflammation
In their study published in the journal "Allergy", the official journal of the European Academy of Allergy and Clinical Immunology, they proposed a new therapeutic approach based on modulation of the immune system by injecting Fel d 1 in combination with high doses of the adjuvant oligonucleotide CpG. "We wanted to explore new ways to increase anti-inflammatory activity with adjuvant CpG at a safe dose, but at a higher dose than those previously used for this type of therapy. We wanted to explore new ways to increase anti-inflammatory activity with the adjuvant CpG at a safe dose, but at a higher dose than previously used for this type of therapy," said Dr. Cathy Léonard, from the Allergy and Clinical Immunology research group at LIH and first author of the publication.
The scientists therefore proceeded by injecting allergic mice with the allergen Fel d 1 in combination with a high dose of CpG adjuvant to study the effects of this immunotherapy on the alleviation of cat allergy symptoms. They observed that, compared to allergic mice that did not receive the treatment, the treated allergic mice showed significantly reduced signs of inflammation and airway hyperreactivity, lower levels of pro-allergic molecules (called cytokines) and IgE antibodies commonly associated with allergic responses, as well as higher levels of protective IgA and IgG antibodies.
Simplified therapy
The researchers also noticed that shortly after injection, an increase in the number of immune cells involved in regulation and tolerance, namely plasmacytoid dendritic cells (pDCs), Natural Killer cells, regulatory T-cells (T-regs) and regulatory B-cells (B-regs). These cells express higher levels of specific molecules and associated receptors, allowing them to suppress the allergen-related immune response and act as a brake on the immune system. These results demonstrate the powerful anti-inflammatory and anti-allergic effect of their approach, with a high and safe dose of CpG adjuvant.
"We propose a preclinical model of allergen-specific immunotherapy (AIT) for cat allergy, mimicking the conditions required for human clinical trials and already optimized for future use in translational studies. Our study presents several novel features, including the use of a safe variant of the allergen Fel d 1, which is mandatory in clinical settings to avoid collateral inflammatory reactions. We show that the use of the maximum tolerated human dose of CpG in combination with Fel d 1 has the ability to modulate the allergic response, with a very favorable safety profile. "The researchers note.
Based on their data, they conclude that CpG deserves to be reconsidered as an effective adjunct for allergen-specific immunotherapy in humans in general and that their discovery lays the foundation for the development of new and effective immunotherapeutic treatments for allergies. Allergies can have cutaneous (urticaria, dermatitis), respiratory (rhinitis, asthma) or generalized (anaphylaxis) manifestations and their prevalence has increased considerably over the last 20-30 years in industrialized countries. Inserm now estimates that 25-30% of the population is affected by an allergic disease.
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