TY  - JOUR
U1  - Zeitschriftenartikel, wissenschaftlich - begutachtet (reviewed)
A1  - Spohn, Gunther
A1  - Schwarz, Katrin
A1  - Maurer, Patrik
A1  - Illges, Harald
A1  - Rajasekaran, Narendiran
A1  - Choi, Yongwon
A1  - Jennings, Gary T.
A1  - Bachmann, Martin F.
T1  - Protection against osteoporosis by active immunization with TRANCE/RANKL displayed on virus-like particles
JF  - J Immunol. (The Journal of Immunology)
N2  - 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.
SN  - 0022-1767
SS  - 0022-1767
U6  - https://doi.org/10.4049/jimmunol.175.9.6211
DO  - https://doi.org/10.4049/jimmunol.175.9.6211
PM  - 16237119
VL  - 175
IS  - 9
SP  - 6211
EP  - 6218
PB  - The American Association of Immunologists
ER  -