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...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2005-11, Vol.175 (9), p.6211-6218
Main Authors: Spohn, Gunther, Schwarz, Katrin, Maurer, Patrik, Illges, Harald, Rajasekaran, Narendiran, Choi, Yongwon, Jennings, Gary T, Bachmann, Martin F
Format: Article
Language:English
Subjects:
Animals
B-Lymphocytes - immunology
Carrier Proteins - immunology
Female
Membrane Glycoproteins - immunology
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Osteoporosis - prevention & control
Ovariectomy
RANK Ligand
Receptor Activator of Nuclear Factor-kappa B
Vaccination
Virion - immunology
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.175.9.6211