Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 64, Issue -, Pages 326-332Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.intimp.2018.09.022
Keywords
Rheumatoid arthritis; RANKL; Vaccine; Unnatural amino acid; Immunization
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Funding
- Science and Technology Innovation Project in Shaanxi Province of China [2015KTCL03-09]
- National Natural Science Foundation of China [81070698]
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Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammatory synovitis, bone atrophy, and subsequent progressive destruction of articular tissue. Targeted inhibition of receptor activator of NF-kappa B ligand (RANKL) has been highly successful in preventing RA-mediated bone erosion in animal models and patients, suggesting that development of a RANKL vaccine might be of therapeutic value. Our previous study has shown that the recombinant RANKL vaccine Y(234)pNO(2)Phe, generated by replacement of a single tyrosine residue (Tyr(234)) in murine RANKL (mRANKL) with p-nitrophenylalanine (pNO(2)Phe), induces a high titer antibody response and prevents ovariectomy (OVX)-induced bone loss in mice. This aim of this study was to further evaluate the vaccine's preventive effects in a murine model of collagen-induced arthritis. The results of this study showed that Y(234)pNO(2) Phe not only induced a high titer antibody response and inhibited osteoclastogenesis but also significantly prevented bone erosion and ameliorated the severity of a collagen-induced arthritis (CIA) model in mice. Moreover, use of the vaccine improved the clinical situations of the CIA mice. These results suggest a potential application of an anti-RANKL vaccine in the treatment of RA-induced bone erosion.
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