title: Development of an Interleukin-1β Vaccine in Patients with Type 2 Diabetes.
abstract: 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).
authors.affiliation: Department of Endocrinology, Diabetes, and Metabolism, University Hospital of Basel, Basel, Switzerland.
authors.forename: Claudia
authors.initials: C
authors.lastname: Cavelti-Weder
authors.affiliation: Department of Endocrinology, Diabetes, and Metabolism, University Hospital of Basel, Basel, Switzerland.
authors.forename: Katharina
authors.initials: K
authors.lastname: Timper
authors.affiliation: Department of Endocrinology, Diabetes, and Metabolism, University Hospital of Basel, Basel, Switzerland.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Seelig
authors.affiliation: Department of Endocrinology, Diabetes, and Metabolism, University Hospital of Zurich, Zurich, Switzerland.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Keller
authors.affiliation: Department of Endocrinology, Diabetes, and Metabolism, University Hospital of Zurich, Zurich, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Osranek
authors.affiliation: Cytos Biotechnology AG, Schlieren, Switzerland.
authors.forename: Ute
authors.initials: U
authors.lastname: Lässing
authors.affiliation: Cytos Biotechnology AG, Schlieren, Switzerland.
authors.forename: Gunther
authors.initials: G
authors.lastname: Spohn
authors.affiliation: Cytos Biotechnology AG, Schlieren, Switzerland.
authors.forename: Patrik
authors.initials: P
authors.lastname: Maurer
authors.affiliation: Cytos Biotechnology AG, Schlieren, Switzerland.
authors.forename: Philipp
authors.initials: P
authors.lastname: Müller
authors.affiliation: Cytos Biotechnology AG, Schlieren, Switzerland.
authors.forename: Gary T
authors.initials: GT
authors.lastname: Jennings
authors.affiliation: Cytos Biotechnology AG, Schlieren, Switzerland.
authors.forename: Joerg
authors.initials: J
authors.lastname: Willers
authors.affiliation: Cytos Biotechnology AG, Schlieren, Switzerland.
authors.forename: Philippe
authors.initials: P
authors.lastname: Saudan
authors.affiliation: Department of Endocrinology, Diabetes, and Metabolism, University Hospital of Basel, Basel, Switzerland.
authors.forename: Marc Y
authors.initials: MY
authors.lastname: Donath
authors.affiliation: Cytos Biotechnology AG, Schlieren, Switzerland.
authors.forename: Martin F
authors.initials: MF
authors.lastname: Bachmann
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D057134:Antibodies, Neutralizing / Q000008:administration & dosage*; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology / Q000628:therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000276:immunology*; D008253:Macaca mulatta; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D014612:Vaccines / Q000008:administration & dosage* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D053583:Interleukin-1beta; D014612:Vaccines