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Veterinary sciences2024; 11(10); 476; doi: 10.3390/vetsci11100476

Phenotypic Shift of an Inflammatory Eosinophil Subset into a Steady-State Resident Phenotype after 2 Years of Vaccination against IL-5 in Equine Insect Bite Hypersensitivity.

Abstract: Eosinophils play a key role in allergic diseases such as insect bite hypersensitivity (IBH). Together with Th2 cells, they shape the course of inflammation in associated type I/IVb allergies. Therefore, a virus-like particle (VLP)-based vaccine targeting equine interleukin-5 (eIL-5), eIL-5-CuMV-TT, was developed to interfere with the IL-5 dependency of eosinophils by inducing the production of anti-self-IL-5 antibodies and alleviating clinical signs in IBH-affected horses. A previous study highlighted the presence of two eosinophil subsets, steady-state resident eosinophils (rEos) and inflammatory eosinophils (iEos), circulating in the blood of healthy and IBH-affected horses, distinguishable by the expression of integrin CD49f. Furthermore, eIL-5-CuMV-TT 1st year vaccination showed a significant decrease of total eosinophils and, in particular, iEos. Nevertheless, the very few remaining eosinophils still shared an iEos phenotype, reflected by bigger size and higher granularity. The aim of this study was to follow up on the phenotype of eosinophils in the 2nd year of vaccination of IBH-affected horses with eIL-5-CuMV-TT. Using flow cytometry analysis of the blood of healthy, IBH, IBH-placebo, and IBH-vaccinated horses, the percentage and count of cells were compared between groups with a focus on pair analysis of eosinophils in 1st and 2nd year vaccinated horses. Our data showed comparably low levels of iEos and a significant increase of rEos in 2nd year compared to 1st year vaccinated horses, suggesting a phenotypic shift toward a resident-like eosinophil population, primarily associated with the phenotype of healthy horses. The reduction of size, granularity, and expression of integrin CD49f in the 2nd year suggests a benefit of long-term treatment with the eIL-5-CuMV-TT vaccine.
Publication Date: 2024-10-05 PubMed ID: 39453068DOI: 10.3390/vetsci11100476Google Scholar: Lookup
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Summary

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The research explores the changes in a subtype of eosinophils in the blood of horses suffering from insect bite hypersensitivity (IBH), resulting from their vaccination against IL-5 for two years. This then reduces the severity of their allergy symptoms.

Overview and Introduction

  • This study focuses on eosinophils, these are white blood cells that play a critical role in allergic diseases like Insect Bite Hypersensitivity (IBH).
  • The research develops on previous findings which identified two distinct types of eosinophils: steady-state resident eosinophils (rEos) and inflammatory eosinophils (iEos).
  • These types of eosinophils could be distinguished by their expression of integrin CD49f, a kind of protein that aids the movement and activation of eosinophils.

Methods and Vaccine Treatment

  • The investigation used a virus-like particle (VLP)-based vaccine targeting equine interleukin-5 (the signaling molecule involved in the differentiation and activation of eosinophils, referred to as eIL-5 in the study) in an attempt to interfere with the role of IL-5 in IBH.
  • The vaccine, named eIL-5-CuMV-TT, stimulated the production of antibodies against IL-5 and was expected to alleviate the clinical symptoms in IBH-affected horses.
  • The scientists tracked the behavior and quantities of eosinophils in vaccinated horses for two years to understand the vaccine’s long-term effects.

Findings and Conclusion

  • The results from the first year of vaccination showed a significant reduction in total eosinophils and specifically, iEos. However, the remaining eosinophils still possessed the inflammatory phenotype similar to iEos, as indicated by their larger size and higher granularity.
  • In the second year, the researchers noticed relatively low levels of iEos and a significant increase of rEos in vaccinated horses, suggesting a shift in the eosinophils subtype.
  • The alteration in the size, granularity, and expression of integrin CD49f in eosinophils during the second year suggests a benefit of extended treatment with the eIL-5-CuMV-TT vaccine, showing its impact on shifting the eosinophils towards a phenotype resembling that found in healthy horses.

Cite This Article

APA
Schwarz E, Jebbawi F, Keller G, Rhiner T, Fricker A, Waldern N, Canonica F, Schoster A, Fettelschoss-Gabriel A. (2024). Phenotypic Shift of an Inflammatory Eosinophil Subset into a Steady-State Resident Phenotype after 2 Years of Vaccination against IL-5 in Equine Insect Bite Hypersensitivity. Vet Sci, 11(10), 476. https://doi.org/10.3390/vetsci11100476

Publication

ISSN: 2306-7381
NlmUniqueID: 101680127
Country: Switzerland
Language: English
Volume: 11
Issue: 10
PII: 476

Researcher Affiliations

Schwarz, Elio
  • Evax AG, Im Binz 3, 8357 Guntershausen, Switzerland.
Jebbawi, Fadi
  • Evax AG, Im Binz 3, 8357 Guntershausen, Switzerland.
  • Department of Dermatology, University Hospital Zurich, 8091 Schlieren, Switzerland.
  • Faculty of Medicine, University of Zurich, 8006 Zurich, Switzerland.
Keller, Giulia
  • Evax AG, Im Binz 3, 8357 Guntershausen, Switzerland.
  • Department of Dermatology, University Hospital Zurich, 8091 Schlieren, Switzerland.
  • Faculty of Medicine, University of Zurich, 8006 Zurich, Switzerland.
Rhiner, Tanya
  • Evax AG, Im Binz 3, 8357 Guntershausen, Switzerland.
  • Equine Department, Vetsuisse Faculty, University of Zurich, 8006 Zurich, Switzerland.
Fricker, Anna
  • Evax AG, Im Binz 3, 8357 Guntershausen, Switzerland.
Waldern, Nina
  • Evax AG, Im Binz 3, 8357 Guntershausen, Switzerland.
Canonica, Fabia
  • Evax AG, Im Binz 3, 8357 Guntershausen, Switzerland.
  • Department of Dermatology, University Hospital Zurich, 8091 Schlieren, Switzerland.
  • Faculty of Medicine, University of Zurich, 8006 Zurich, Switzerland.
Schoster, Angelika
  • Equine Department, Vetsuisse Faculty, University of Zurich, 8006 Zurich, Switzerland.
Fettelschoss-Gabriel, Antonia
  • Evax AG, Im Binz 3, 8357 Guntershausen, Switzerland.
  • Department of Dermatology, University Hospital Zurich, 8091 Schlieren, Switzerland.
  • Faculty of Medicine, University of Zurich, 8006 Zurich, Switzerland.

Grant Funding

  • Bridge, grant number 40B2-0_194689 for AF-G / Swiss National Science Foundation
  • (CH) / EVAX AG

Citations

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