Anti-IL-5 Vaccination Dampens Allergen-Specific IgE Levels and Modulates IL-4 and IL-5 Th2 Cytokines in Skin Allergy of Mice and Horses.
Abstract: Skin allergies are among the most frequent types of allergies, where continuous investigation of the pathological immune mechanisms is required for a better understanding and a more effective treatment of the disease. In this study, we aimed to investigate the effect of interleukin (IL)-5 vaccination on allergen-specific IgE antibodies as well as T cell cytokine modulation in skin allergy using a mouse model and a naturally occurring disease in horses. Methods: Ovalbumin (OVA)-sensitized mice, as well as horses affected by equine insect bite hypersensitivity (IBH) were administered an anti-IL-5 vaccination, and allergen-specific IgE and IgG were quantified in the blood. Additionally, mRNA and protein expression of T cell cytokines of in vitro allergen re-stimulated murine splenocytes and equine peripheral blood mononuclear cells (PBMCs), as well as in IBH lesional skin biopsies, were investigated using qPCR and ELISA. Clinical signs were recorded by ear swelling in mice. Results: Our data showed a significant decrease in allergen-specific immunoglobulins (Igs) in IL-5-vaccinated mice, as well as a reduction in allergen-specific IgE in horses. Furthermore, protein production of T cell cytokines IL-4 and IFNγ in mice, as well as mRNA expression of IL-4, IL-5, IL-13, and IFNγ in lesional skin of the horses, was significantly decreased upon vaccination when compared to the placebo group. Furthermore, we demonstrated that CD4 cells in IBH-affected horses are highly enriched with the GATA3 transcription factor, responsible for IL-5 mRNA production and differentiation of Th2 cells. Additionally, increased IL-4 mRNA expression in IBH horses was shown to be CD4MHC-IIcell dependent. Conclusions: IL-5 vaccination significantly decreased allergen-specific IgE in both the murine skin allergy model and horses with naturally occurring allergic skin disease, as well as alleviated clinical signs of the diseases. We suggest that the IL-5 depletion may modulate the IL-4 levels originating from non-T cell sources. This is the first study showing that an IL-5 vaccination leads to a decrease in allergen-specific IgE levels, potentially suggesting its use in prophylactic settings for high-risk patients.
© 2025 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.
Publication Date: 2025-08-21 PubMed ID: 40838325PubMed Central: PMC12666748DOI: 10.1111/all.70020Google Scholar: Lookup
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- Journal Article
Summary
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Overview
- This study investigates how vaccination against interleukin-5 (IL-5) affects allergen-specific immune responses, particularly IgE antibody levels and T helper 2 (Th2) cytokines, in skin allergies using both mice and horses as model systems.
- The findings reveal that anti-IL-5 vaccination reduces allergen-specific IgE levels and modulates Th2 cytokines, which may help alleviate allergic symptoms and suggest potential therapeutic benefits for allergic skin diseases.
Background and Objectives
- Skin allergies are common and involve complex immune system reactions that are not fully understood.
- Interleukin-5 (IL-5) is a cytokine involved in the promotion of eosinophils and Th2 immune responses, both key players in allergic inflammation.
- The study aimed to explore the effect of an anti-IL-5 vaccine on:
- Allergen-specific immunoglobulin E (IgE) and immunoglobulin G (IgG) antibody levels.
- The modulation of T cell cytokines related to Th2 immune responses, such as IL-4, IL-5, and IL-13, as well as interferon gamma (IFNγ) which is involved in Th1 responses.
- Clinical allergy symptoms in both a controlled mouse model and naturally occurring equine insect bite hypersensitivity (IBH), a type of allergic skin disease in horses.
Methods
- Animals and Treatments:
- Mice were sensitized with ovalbumin (OVA) to induce a skin allergic response and subsequently vaccinated with an anti-IL-5 vaccine.
- Horses affected by IBH, an allergic skin disease caused by insect bites, were also vaccinated with the anti-IL-5 formulation.
- Immunological Assessments:
- Measurement of allergen-specific IgE and IgG antibodies in the blood using serological tests.
- Quantification of T cell cytokine expression at both mRNA and protein levels:
- Murine splenocytes and equine peripheral blood mononuclear cells (PBMCs) were stimulated in vitro with allergens to assess cytokine responses.
- Lesional skin biopsies from horses were analyzed by qPCR and ELISA to determine local cytokine expression.
- Clinical Evaluation:
- In mice, allergen-induced ear swelling was recorded as a measure of allergic inflammation.
Key Results
- Reduction in Allergen-Specific Antibodies:
- IL-5 vaccination led to a significant decrease in allergen-specific IgE and IgG in mice.
- Significant reduction in allergen-specific IgE was also observed in IBH-affected horses after vaccination.
- Altered Cytokine Profiles:
- Mice showed decreased protein levels of IL-4 and IFNγ following vaccination.
- In horses, mRNA levels of IL-4, IL-5, IL-13, and IFNγ in lesional skin were significantly decreased in vaccinated animals compared to placebo controls.
- Immunological Insights:
- CD4+ T cells in horses with IBH were found to be enriched in the transcription factor GATA3, which promotes IL-5 production and Th2 cell differentiation.
- IL-4 expression in IBH horses appeared to depend on interactions between CD4+ T cells and MHC-II expressing cells, suggesting an immune cell collaboration in cytokine production.
- Clinical Improvement:
- Mice vaccinated with anti-IL-5 exhibited alleviation of allergic clinical signs such as ear swelling.
Conclusions and Implications
- Anti-IL-5 vaccination successfully decreased allergen-specific IgE levels and modulated Th2 cytokine responses associated with allergic skin diseases.
- The modulation of IL-4—possibly originating from non-T cell sources due to IL-5 depletion—suggests a broader immunoregulatory effect of the vaccination.
- This study provides the first evidence that targeting IL-5 via vaccination can reduce allergen-specific IgE, which is a key factor in allergic reactions.
- The findings indicate potential use of IL-5 vaccination as a prophylactic or therapeutic approach in animals and potentially humans at high risk of skin allergies.
- Further research may explore the role of IL-5 vaccines in other allergic diseases and the underlying mechanisms of immune modulation.
Cite This Article
APA
Jebbawi F, Olomski F, Inversini V, Keller G, Rhiner T, Waldern N, Lam J, Pantelyushin S, Canonica F, Birkmann K, Johansen P, Kündig TM, Fettelschoss-Gabriel A.
(2025).
Anti-IL-5 Vaccination Dampens Allergen-Specific IgE Levels and Modulates IL-4 and IL-5 Th2 Cytokines in Skin Allergy of Mice and Horses.
Allergy, 80(12), 3377-3390.
https://doi.org/10.1111/all.70020 Publication
Researcher Affiliations
- Department of Dermatology, University Hospital Zurich, Schlieren, Switzerland.
- Faculty of Medicine, University of Zurich, Zürich, Switzerland.
- Evax AG, Guntershausen, Switzerland.
- Department of Dermatology, University Hospital Zurich, Schlieren, Switzerland.
- Faculty of Medicine, University of Zurich, Zürich, Switzerland.
- Evax AG, Guntershausen, Switzerland.
- Department of Dermatology, University Hospital Zurich, Schlieren, Switzerland.
- Faculty of Medicine, University of Zurich, Zürich, Switzerland.
- Evax AG, Guntershausen, Switzerland.
- Department of Dermatology, University Hospital Zurich, Schlieren, Switzerland.
- Faculty of Medicine, University of Zurich, Zürich, Switzerland.
- Evax AG, Guntershausen, Switzerland.
- Department of Dermatology, University Hospital Zurich, Schlieren, Switzerland.
- Evax AG, Guntershausen, Switzerland.
- Evax AG, Guntershausen, Switzerland.
- Department of Dermatology, University Hospital Zurich, Schlieren, Switzerland.
- Faculty of Medicine, University of Zurich, Zürich, Switzerland.
- Evax AG, Guntershausen, Switzerland.
- Department of Dermatology, University Hospital Zurich, Schlieren, Switzerland.
- Faculty of Medicine, University of Zurich, Zürich, Switzerland.
- Evax AG, Guntershausen, Switzerland.
- Department of Dermatology, University Hospital Zurich, Schlieren, Switzerland.
- Faculty of Medicine, University of Zurich, Zürich, Switzerland.
- Evax AG, Guntershausen, Switzerland.
- Evax AG, Guntershausen, Switzerland.
- Equine Department, Veterinary Faculty, Ludwig Maximilians University Munich LMU, Oberschleißheim, Germany.
- Department of Dermatology, University Hospital Zurich, Schlieren, Switzerland.
- Faculty of Medicine, University of Zurich, Zürich, Switzerland.
- Department of Dermatology, University Hospital Zurich, Schlieren, Switzerland.
- Faculty of Medicine, University of Zurich, Zürich, Switzerland.
- Department of Dermatology, University Hospital Zurich, Schlieren, Switzerland.
- Faculty of Medicine, University of Zurich, Zürich, Switzerland.
- Evax AG, Guntershausen, Switzerland.
MeSH Terms
- Animals
- Horses
- Immunoglobulin E / immunology
- Immunoglobulin E / blood
- Mice
- Interleukin-5 / immunology
- Interleukin-5 / antagonists & inhibitors
- Allergens / immunology
- Interleukin-4 / metabolism
- Interleukin-4 / immunology
- Cytokines / metabolism
- Th2 Cells / immunology
- Th2 Cells / metabolism
- Vaccination
- Disease Models, Animal
- Female
- Horse Diseases / immunology
- Dermatitis, Atopic / immunology
- Hypersensitivity / immunology
- Insect Bites and Stings / immunology
Grant Funding
- EVAX AG (CH)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Kommission für Technologie und Innovation (KTI)
Conflict of Interest Statement
F.J., V.I., G.K., T.R., N.W., J.L., F.C., K.B., T.M.K., and A.F.‐G. are involved in the development of therapeutic equine vaccines. F.O., S.P., and P.J. have no financial or personal conflicts of interest.
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Citations
This article has been cited 1 times.- Wichtowska A, Olejnik M. Anti-Cytokine Drugs in the Treatment of Canine Atopic Dermatitis.. Int J Mol Sci 2025 Nov 13;26(22).
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