期刊
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
卷 1, 期 -, 页码 -出版社
CELL PRESS
DOI: 10.1038/mtm.2014.48
关键词
-
资金
- Swiss National Science Foundation [31003A_149925]
Neutralization of the inflammatory cytokine interleukin-1 beta (IL-1 beta) is a promising new strategy to prevent the beta-cell destruction, which leads to type 2 diabetes. Here, we describe the preclinical development of a therapeutic vaccine against IL-1 beta consisting of a detoxified version of IL-1 beta chemically cross-linked to virus-like particles of the bacteriophage Q beta. The vaccine was well tolerated and induced robust antibody responses in mice, which neutralized the biological activity of IL-1 beta, 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-1 beta. Neutralization of IL-1 beta 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 beta-cells. Hence, immunization with IL-1 beta 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.
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