preclinical efficacy and safety of an anti-il-1β vaccine for the treatment of type 2 diabetes
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2014
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Abstract
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.
| Reference Key |
spohn2014molecularpreclinical
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| Authors | ;Gunther Spohn;Christian Schori;Iris Keller;Katja Sladko;Christina Sina;Reto Guler;Katrin Schwarz;Pål Johansen;Gary T Jennings;Martin F Bachmann |
| Journal | international journal of zoology |
| Year | 2014 |
| DOI |
10.1038/mtm.2014.48
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| URL | |
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