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

Cavelti-Weder, Claudia; Timper, Katharina; Seelig, Eleonora; Keller, Cornelia; Osranek, Martin; Lässing, Ute; Spohn, Gunther; Maurer, Patrik; Müller, Philipp; Jennings, Gary T; Willers, Joerg; Saudan, Philippe; Donath, Marc Y; Bachmann, Martin (2016). Development of an Interleukin-1β Vaccine in Patients with Type 2 Diabetes. Molecular therapy, 24(5), pp. 1003-1012. Nature Publishing Group 10.1038/mt.2015.227

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Interleukin-1β (IL-1β) 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-1β 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-1β. The vaccine hIL1bQb consisting of full-length, recombinant IL-1β 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-1β-specific antibodies upon vaccination, while neutralizing antibodies appeared with delay. In the clinical study with 48 type 2 diabetic patients, neutralizing IL-1β-specific antibody responses were detectable after six injections with doses of 900 µg. 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-1β and represents a new treatment option for IL-1β-dependent diseases such as type 2 diabetes mellitus (ClinicalTrials.gov NCT00924105).Molecular Therapy (2016); doi:10.1038/mt.2015.227.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology, Clinical Immunology and Allergology

UniBE Contributor:

Bachmann, Martin

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1525-0016

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Nathalie Taiana

Date Deposited:

02 Mar 2016 10:50

Last Modified:

01 Jun 2016 10:59

Publisher DOI:

10.1038/mt.2015.227

PubMed ID:

26686385

URI:

https://boris.unibe.ch/id/eprint/76237

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