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

Jonsdottir, Sigridur; Fettelschoss, Victoria; Olomski, Florian; Talker, Stephanie C.; Mirkovitch, Jelena; Rhiner, Tanya; Birkmann, Katharina; Thoms, Franziska; Wagner, Bettina; Bachmann, Martin F.; Kündig, Thomas M.; Marti, Eliane Isabelle; Fettelschoss-Gabriel, Antonia (2020). Safety Profile of a Virus-Like Particle-Based Vaccine Targeting Self-Protein Interleukin-5 in Horses. Vaccines, 8(2) MDPI 10.3390/vaccines8020213

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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-CuMVTT) 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-CuMVTT vaccine. Methods: The B cell responses were assessed by longitudinal measurement of IL-5- and CuMVTT-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 CuMVTT 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-CuMVTT induces a strong B-cell as well as CuMVTT-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 CuMVTT carrier-specific T cells, making the vaccine a safe therapeutic option for IBH-affected horses.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Experimental Clinical Research
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology, Clinical Immunology and Allergology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Virology and Immunology
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH)

UniBE Contributor:

Jonsdottir, Sigridur; Talker, Stephanie; Mirkovitch, Jelena; Bachmann, Martin and Marti, Eliane Isabelle

Subjects:

600 Technology > 610 Medicine & health
600 Technology > 630 Agriculture

ISSN:

2076-393X

Publisher:

MDPI

Language:

English

Submitter:

Lee-Anne Brand

Date Deposited:

11 Nov 2020 11:44

Last Modified:

11 Nov 2020 11:44

Publisher DOI:

10.3390/vaccines8020213

PubMed ID:

32397549

Uncontrolled Keywords:

safety self-protein therapeutic vaccine

BORIS DOI:

10.7892/boris.147999

URI:

https://boris.unibe.ch/id/eprint/147999

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