Development of an Interleukin-1 beta Vaccine in Patients with Type 2 Diabetes

作者：Cavelti Weder Claudia; Timper Katharina; Seelig Eleonora; Keller Cornelia; Osranek Martin; Lassing Ute; Spohn Gunther; Maurer Patrik; Mueller Philipp; Jennings Gary T; Willers Joerg; Saudan Philippe; Donath Marc Y^*; Bachmann Martin F

来源：Molecular Therapy, 2016, 24(5): 1003-1012.

DOI：10.1038/mt.2015.227

Interleukin-1 beta (IL-1 beta) is a key cytokine involved in inflammatory illnesses including rare hereditary diseases and common chronic inflammatory conditions as gout, rheumatoid arthritis, and type 2 diabetes mellitus, suggesting reduction of IL-1 beta activity as new treatment strategy. The objective of our study was to assess safety, antibody response, and preliminary efficacy of a novel vaccine against IL-1 beta. The vaccine hIL1bQb consisting of full-length, recombinant IL-1 beta coupled to virus-like particles was tested in a preclinical and clinical, randomized, placebo-controlled, double-blind study in patients with type 2 diabetes. The preclinical simian study showed prompt induction of IL-1 beta-specific antibodies upon vaccination, while neutralizing antibodies appeared with delay. In the clinical study with 48 type 2 diabetic patients, neutralizing IL-1 beta-specific antibody responses were detectable after six injections with doses of 900 mu g. The development of neutralizing antibodies was associated with higher number of study drug injections, lower baseline body mass index, improvement of glycemia, and C-reactive protein (CRP). The vaccine hIL1bQb was safe and well-tolerated with no differences regarding adverse events between patients receiving hIL1bQb compared to placebo. This is the first description of a vaccine against IL-1 beta and represents a new treatment option for IL-1 beta-dependent diseases such as type 2 diabetes mellitus

• 出版日期2016-5