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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.

Original publication

DOI

10.4049/jimmunol.175.9.6211

Type

Journal article

Journal

J Immunol

Publication Date

01/11/2005

Volume

175

Pages

6211 - 6218

Keywords

Animals, B-Lymphocytes, Carrier Proteins, Female, Membrane Glycoproteins, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Osteoporosis, Ovariectomy, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B, Vaccination, Virion