title: Preclinical efficacy and safety of an anti-IL-1β vaccine for the treatment of type 2 diabetes.
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.
authors.affiliation: Cytos Biotechnology , Schlieren, Switzerland.
authors.forename: Gunther
authors.initials: G
authors.lastname: Spohn
authors.affiliation: Cytos Biotechnology , Schlieren, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Schori
authors.affiliation: Cytos Biotechnology , Schlieren, Switzerland.
authors.forename: Iris
authors.initials: I
authors.lastname: Keller
authors.affiliation: Cytos Biotechnology , Schlieren, Switzerland.
authors.forename: Katja
authors.initials: K
authors.lastname: Sladko
authors.affiliation: Cytos Biotechnology , Schlieren, Switzerland.
authors.forename: Christina
authors.initials: C
authors.lastname: Sina
authors.affiliation: International Centre for Genetic Engineering and Biotechnology (ICGEB) and Institute of Infectious Diseases and Molecular Medicine (IDM), Division of Immunology, University of Cape Town , Cape Town, South Africa.
authors.forename: Reto
authors.initials: R
authors.lastname: Guler
authors.affiliation: Cytos Biotechnology , Schlieren, Switzerland.
authors.forename: Katrin
authors.initials: K
authors.lastname: Schwarz
authors.affiliation: Department of Dermatology, University Hospital of Zurich , Zurich, Switzerland.
authors.forename: Pål
authors.initials: P
authors.lastname: Johansen
authors.affiliation: Cytos Biotechnology , Schlieren, Switzerland.
authors.forename: Gary T
authors.initials: GT
authors.lastname: Jennings
authors.affiliation: Cytos Biotechnology , Schlieren, Switzerland.
authors.forename: Martin F
authors.initials: MF
authors.lastname: Bachmann