Safety Profile of a Virus-Like Particle-Based Vaccine Targeting Self-Protein Interleukin-5 in Horses

Sigridur Jonsdottir; Victoria Fettelschoss; Florian Olomski; Stephanie C Talker; Jelena Mirkovitch; Tanya Rhiner; Katharina Birkmann; Franziska Thoms; Bettina Wagner; Martin F Bachmann; Thomas M Kündig; Eliane Marti; Antonia Fettelschoss-Gabriel

doi:10.3390/vaccines8020213

Safety Profile of a Virus-Like Particle-Based Vaccine Targeting Self-Protein Interleukin-5 in Horses

Vaccines (Basel). 2020 May 9;8(2):213. doi: 10.3390/vaccines8020213.

Authors

Sigridur Jonsdottir^{1

2

3}, Victoria Fettelschoss^{2

3

4}, Florian Olomski^{2

3}, Stephanie C Talker^{5

6}, Jelena Mirkovitch¹, Tanya Rhiner^{2

3}, Katharina Birkmann⁴, Franziska Thoms^{2

3}, Bettina Wagner⁷, Martin F Bachmann^{8

9}, Thomas M Kündig¹⁰, Eliane Marti¹, Antonia Fettelschoss-Gabriel^{2

3

4}

Affiliations

¹ Clinical Immunology Group, Department for Clinical Research VPH, Vetsuisse Faculty of the University of Bern, Länggassstrasse 124, 3012 Bern, Switzerland.
² Department of Dermatology, University Hospital Zurich, Wagistrasse 12, 8952 Schlieren, Switzerland.
³ Faculty of Medicine University of Zurich, 8091 Zurich, Switzerland.
⁴ Evax AG, Hörnlistrass 3, 9542 Münchwilen, Switzerland.
⁵ Institute of Virology and Immunology, Länggassstrasse 122, 3012 Bern, Switzerland.
⁶ Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Länggassstrasse 122, 3012 Bern, Switzerland.
⁷ Departments of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, 14853-0001 NY, USA.
⁸ RIA Immunology, Inselspital, University of Bern, 3012 Bern, Switzerland.
⁹ Jenner Institute, Nuffield Department of Medicine, Henry Welcome Building for Molecular Physiology, University of Oxford, OX1 2JD Oxford, UK.
¹⁰ Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland.

Abstract

：Background: Insect bite hypersensitivity (IBH) is an eosinophilic allergic dermatitis of horses caused by type I/IVb reactions against mainly Culicoides bites. The vaccination of IBH-affected horses with equine IL-5 coupled to the Cucumber mosaic virus-like particle (eIL-5-CuMV_TT) induces IL-5-specific auto-antibodies, resulting in a significant reduction in eosinophil levels in blood and clinical signs. Objective: the preclinical and clinical safety of the eIL-5-CuMV_TT vaccine. Methods: The B cell responses were assessed by longitudinal measurement of IL-5- and CuMV_TT-specific IgG in the serum and plasma of vaccinated and unvaccinated horses. Further, peripheral blood mononuclear cells (PBMCs) from the same horses were re-stimulated in vitro for the proliferation and IFN-γ production of specific T cells. In addition, we evaluated longitudinal kidney and liver parameters and the general blood status. An endogenous protein challenge was performed in murine IL-5-vaccinated mice. Results: The vaccine was well tolerated as assessed by serum and cellular biomarkers and also induced reversible and neutralizing antibody titers in horses and mice. Endogenous IL-5 stimulation was unable to re-induce anti-IL-5 production. The CD4⁺ T cells of vaccinated horses produced significantly more IFN-γ and showed a stronger proliferation following stimulation with CuMV_TT as compared to the unvaccinated controls. Re-stimulation using E. coli-derived proteins induced low levels of IFNγ⁺CD4⁺ cells in vaccinated horses; however, no IFN-γ and proliferation were induced following the HEK-eIL-5 re-stimulation. Conclusions: Vaccination using eIL-5-CuMV_TT induces a strong B-cell as well as CuMV_TT-specific T cell response without the induction of IL-5-specific T cell responses. Hence, B-cell unresponsiveness against self-IL-5 can be bypassed by inducing CuMV_TT carrier-specific T cells, making the vaccine a safe therapeutic option for IBH-affected horses.

Keywords: safety; self-protein; therapeutic vaccine.

Abstract

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