title: Protection against osteoporosis by active immunization with TRANCE/RANKL displayed on virus-like particles.
abstract: TNF-related activation-induced cytokine (TRANCE), also known as receptor activator of NF-kappaB ligand (RANKL), is the key molecule responsible for the bone loss observed in osteoporosis. Passive administration of osteoprotegerin, the soluble decoy receptor of TRANCE/RANKL, is efficient in blocking disease progression, but may not find widespread clinical use due to patient compliance problems and the expected high costs. In this study, we describe an efficient, safe, and potentially cost-effective active immunization strategy against TRANCE/RANKL. We show in mice that immunization with TRANCE/RANKL covalently linked to virus-like particles can overcome the natural tolerance of the immune system toward self proteins and produce high levels of specific Abs without the addition of any adjuvant. Serum Abs of immunized mice neutralized TRANCE/RANKL activity in vitro and were highly active in preventing bone loss in a mouse model of osteoporosis. Active immunization against TRANCE/RANKL was essentially reversible and did not produce any measurable immunosuppressive side effects, underscoring its potential as a new therapeutic approach to the treatment of human bone-degenerative disorders.
authors.affiliation: Cytos Biotechnology, Zürich-Schlieren, Switzerland. ganther.spohn@cytos.com
authors.forename: Gunther
authors.initials: G
authors.lastname: Spohn
authors.forename: Katrin
authors.initials: K
authors.lastname: Schwarz
authors.forename: Patrik
authors.initials: P
authors.lastname: Maurer
authors.forename: Harald
authors.initials: H
authors.lastname: Illges
authors.forename: Narendiran
authors.initials: N
authors.lastname: Rajasekaran
authors.forename: Yongwon
authors.initials: Y
authors.lastname: Choi
authors.forename: Gary T
authors.initials: GT
authors.lastname: Jennings
authors.forename: Martin F
authors.initials: MF
authors.lastname: Bachmann
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology*; D005260:Female; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010024:Osteoporosis / Q000517:prevention & control*; D010052:Ovariectomy; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D014611:Vaccination; D014771:Virion / Q000276:immunology*
chemical_list: D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse