Preclinical efficacy and safety of an anti-IL-1β vaccine for the treatment of type 2 diabetes
| Autor: | Gunther Spohn, Christian Schori, Iris Keller, Katja Sladko, Christina Sina, Reto Guler, Katrin Schwarz, Pål Johansen, Gary T Jennings, Martin F Bachmann |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: | |
| Zdroj: | Molecular Therapy: Methods & Clinical Development, Vol 1, Iss C (2014) |
| Druh dokumentu: | article |
| ISSN: | 2329-0501 34554394 |
| DOI: | 10.1038/mtm.2014.48 |
| Popis: | Neutralization of the inflammatory cytokine interleukin-1β (IL-1β) is a promising new strategy to prevent the β-cell destruction, which leads to type 2 diabetes. Here, we describe the preclinical development of a therapeutic vaccine against IL-1β consisting of a detoxified version of IL-1β chemically cross-linked to virus-like particles of the bacteriophage Qβ. The vaccine was well tolerated and induced robust antibody responses in mice, which neutralized the biological activity of IL-1β, as shown both in cellular assays and in challenge experiments in vivo. Antibody titers were long lasting but reversible over time and not associated with the development of potentially harmful T cell responses against IL-1β. Neutralization of IL-1β by vaccine-induced antibodies had no influence on the immune responses of mice to Listeria monocytogenes and Mycobacterium tuberculosis. In a diet-induced model of type 2 diabetes, immunized mice showed improved glucose tolerance, which was mediated by improved insulin secretion by pancreatic β-cells. Hence, immunization with IL-1β conjugated to virus-like particles has the potential to become a safe, efficacious, and cost-effective therapy for the prevention and long-term treatment of type 2 diabetes. |
| Databáze: | Directory of Open Access Journals |
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