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Vaccines2020; 8(2); 213; doi: 10.3390/vaccines8020213

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

Abstract: ： Insect bite hypersensitivity (IBH) is an eosinophilic allergic dermatitis of horses caused by type I/IVb reactions against mainly bites. The vaccination of IBH-affected horses with equine IL-5 coupled to the Cucumber mosaic virus-like particle (eIL-5-CuMV) induces IL-5-specific auto-antibodies, resulting in a significant reduction in eosinophil levels in blood and clinical signs. the preclinical and clinical safety of the eIL-5-CuMV vaccine. The B cell responses were assessed by longitudinal measurement of IL-5- and CuMV-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 as compared to the unvaccinated controls. Re-stimulation using -derived proteins induced low levels of IFNγCD4 cells in vaccinated horses; however, no IFN-γ and proliferation were induced following the HEK-eIL-5 re-stimulation. Vaccination using eIL-5-CuMV induces a strong B-cell as well as CuMV-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 carrier-specific T cells, making the vaccine a safe therapeutic option for IBH-affected horses.
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Publication Date: 2020-05-09 PubMed ID: 32397549PubMed Central: PMC7349629DOI: 10.3390/vaccines8020213Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article is about the efficacy and safety of a Virus-Like Particle-Based Vaccine targeting the self-protein Interleukin-5 in horses suffering from Insect bite hypersensitivity, a common allergic condition in horses.

Background

  • Insect bite hypersensitivity (IBH) is an allergic condition in horses that leads to dermatitis or skin inflammation, triggered by allergen reactions, primarily due to insect bites.
  • The study involves the development and testing of a new vaccine that targets the immune protein, Interleukin-5 (IL-5). This protein plays a key role in promoting the growth and activation of eosinophils, types of white blood cells, whose elevated levels in the blood are associated with allergic reactions such as in IBH.
  • The vaccine is designed using an IL-5 protein derived from horses and linked to the Cucumber mosaic virus-like particle (CuMV). This linkage is intended to initiate an immune response that will generate anti-IL-5 antibodies, reducing eosinophil levels and hence, alleviating the allergic condition.

Methods

  • The research evaluated the safety of the vaccine through assessing B cell responses by measuring IL-5- and CuMV-specific antibodies in the serum and plasma of vaccinated and unvaccinated horses over time.
  • The same horses’ peripheral blood mononuclear cells (a type of immune cell) were stimulated in a lab setting to assess T cell proliferative and Interferon-gamma production responses, providing additional insight into the vaccine’s immune effect.
  • The researchers also assessed kidney and liver parameters, among other general health indicators in the horses, to ensure the vaccine did not cause adverse effects.
  • An endogenous protein challenge was also performed in mice vaccinated with mouse-derived IL-5 to characterize cross-species responses.

Results

  • The study reported that the vaccine was well-tolerated by the test subjects, as judged by the serum and cellular biomarkers. The vaccinated horses and mice exhibited increased antibody titers, an indicator of a robust immune response.
  • The researchers noted that re-stimulation of endogenous IL-5 stimulation did not lead to a resurgence in the production of anti-IL-5, indicating specific and controlled immune activation by the vaccine.
  • The vaccinated horses showed a significant increase in T cells producing Interferon-gamma and in T cell proliferation, especially after stimulation with CuMV, when compared to non-vaccinated controls.
  • There was very little induction of Interferon-gamma producing T cells when stimulated with the allergen, and no Interferon-gamma or proliferation was observed following the re-stimulation with the lab-designed IL-5 protein, illustrating a careful immunomodulation by the vaccine.

Conclusion

  • The research concluded that the IL-5-CuMV vaccine is successful in inducing a strong B-cell and CuMV-specific T cell response, without over-activating IL-5-specific T cells, thereby reducing the risk of autoimmunity.
  • By inducing CuMV carrier-specific T cells, the vaccine learns to bypass the B-cells that would otherwise respond to self-IL-5, making the vaccine a safe and potentially effective therapeutic option for horses affected by IBH.

Cite This Article

APA
Jonsdottir S, Fettelschoss V, Olomski F, Talker SC, Mirkovitch J, Rhiner T, Birkmann K, Thoms F, Wagner B, Bachmann MF, Kündig TM, Marti E, Fettelschoss-Gabriel A. (2020). Safety Profile of a Virus-Like Particle-Based Vaccine Targeting Self-Protein Interleukin-5 in Horses. Vaccines (Basel), 8(2), 213. https://doi.org/10.3390/vaccines8020213

Publication

Vaccines
ISSN: 2076-393X
NlmUniqueID: 101629355
Country: Switzerland
Language: English
Volume: 8
Issue: 2
PII: 213

Researcher Affiliations

Jonsdottir, Sigridur
  • Clinical Immunology Group, Department for Clinical Research VPH, Vetsuisse Faculty of the University of Bern, Länggassstrasse 124, 3012 Bern, Switzerland.
  • Department of Dermatology, University Hospital Zurich, Wagistrasse 12, 8952 Schlieren, Switzerland.
  • Faculty of Medicine University of Zurich, 8091 Zurich, Switzerland.
Fettelschoss, Victoria
  • Department of Dermatology, University Hospital Zurich, Wagistrasse 12, 8952 Schlieren, Switzerland.
  • Faculty of Medicine University of Zurich, 8091 Zurich, Switzerland.
  • Evax AG, Hörnlistrass 3, 9542 Münchwilen, Switzerland.
Olomski, Florian
  • Department of Dermatology, University Hospital Zurich, Wagistrasse 12, 8952 Schlieren, Switzerland.
  • Faculty of Medicine University of Zurich, 8091 Zurich, Switzerland.
Talker, Stephanie C
  • Institute of Virology and Immunology, Länggassstrasse 122, 3012 Bern, Switzerland.
  • Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Länggassstrasse 122, 3012 Bern, Switzerland.
Mirkovitch, Jelena
  • Clinical Immunology Group, Department for Clinical Research VPH, Vetsuisse Faculty of the University of Bern, Länggassstrasse 124, 3012 Bern, Switzerland.
Rhiner, Tanya
  • Department of Dermatology, University Hospital Zurich, Wagistrasse 12, 8952 Schlieren, Switzerland.
  • Faculty of Medicine University of Zurich, 8091 Zurich, Switzerland.
Birkmann, Katharina
  • Evax AG, Hörnlistrass 3, 9542 Münchwilen, Switzerland.
Thoms, Franziska
  • Department of Dermatology, University Hospital Zurich, Wagistrasse 12, 8952 Schlieren, Switzerland.
  • Faculty of Medicine University of Zurich, 8091 Zurich, Switzerland.
Wagner, Bettina
  • Departments of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, 14853-0001 NY, USA.
Bachmann, Martin F
  • RIA Immunology, Inselspital, University of Bern, 3012 Bern, Switzerland.
  • Jenner Institute, Nuffield Department of Medicine, Henry Welcome Building for Molecular Physiology, University of Oxford, OX1 2JD Oxford, UK.
Kündig, Thomas M
  • Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland.
Marti, Eliane
  • Clinical Immunology Group, Department for Clinical Research VPH, Vetsuisse Faculty of the University of Bern, Länggassstrasse 124, 3012 Bern, Switzerland.
Fettelschoss-Gabriel, Antonia
  • Department of Dermatology, University Hospital Zurich, Wagistrasse 12, 8952 Schlieren, Switzerland.
  • Faculty of Medicine University of Zurich, 8091 Zurich, Switzerland.
  • Evax AG, Hörnlistrass 3, 9542 Münchwilen, Switzerland.

Grant Funding

  • 25758.1 PFLS-LS / Kommission fu00fcr Technologie und Innovation
  • n.a. / Evax AG

Conflict of Interest Statement

V.F., K.B, F.T., M.F.B., T.M.K., and A.F.G. are involved in the development of active immunotherapies. The authors S.J., F.O., S.C.T., J.M., T.R., B.W., and E.M. have no conflicts of interest to disclose.

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