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Protection against osteoporosis by active immunization with TRANCE/RANKL displayed on virus-like particles

  • 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.

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Metadaten
Document Type:Article
Language:English
Author:Gunther Spohn, Katrin Schwarz, Patrik Maurer, Harald Illges, Narendiran Rajasekaran, Yongwon Choi, Gary T. Jennings, Martin F. Bachmann
Parent Title (English):J Immunol. (The Journal of Immunology)
Volume:175
Issue:9
First Page:6211
Last Page:6218
ISSN:0022-1767
DOI:https://doi.org/10.4049/jimmunol.175.9.6211
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=16237119
Publisher:The American Association of Immunologists
Date of first publication:2005/11/01
Departments, institutes and facilities:Institut für funktionale Gen-Analytik (IFGA)
Dewey Decimal Classification (DDC):6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Entry in this database:2018/07/25