title: Therapeutic role of a vaccine targeting RANKL and TNF-α on collagen-induced arthritis.
abstract: Targeting tumor necrosis factor-α (TNF-α) and activator of NF-κB ligand (RANKL) has been proved highly successful in rheumatoid arthritis (RA) models and patients. This raises a possibility whether a single agent simultaneously targeting TNF-α and RANKL provides a potential therapeutic opportunity. This study aimed to design a dual functional vaccine and evaluate its therapeutic effects in RA mice model. Standard molecular biological techniques were used to generate human RANKL-TNF-like core fusion protein (RTFP-2) vaccine. High titers of antibodies against human TNF-α and RANKL were elicited and the RTFP-2 antiserum decreased TNF-α mediated apoptosis of L929 cells to 41% compared with 90% in positive controls. In addition, the antiserum completely abrogated osteoclastogenesis in vitro. Immunization with RTFP-2 also reduced the mortality of TNF-α induced cachexia from 56% to 28%. The RANKL-mediated hypercalcemic effects were significantly attenuated in RTFP-2 vaccinated mice. Furthermore, RTFP-2 vaccine significantly mitigated the incidence and severity of CIA via inhibition of inflammation and bone resorption. Our results showed the RTFP-2 vaccine of dual targets ameliorated the symptoms of CIA mice, suggesting the potential possibility to treat inflammatory bone diseases such as RA.
authors.affiliation: Department of Immunology, Institute of Basic Medical Sciences, Beijing, PR China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Yuan
authors.forename: Hongyan
authors.initials: H
authors.lastname: Qian
authors.forename: Sibo
authors.initials: S
authors.lastname: Liu
authors.forename: Xulong
authors.initials: X
authors.lastname: Zhang
authors.forename: Shentao
authors.initials: S
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Zhanguo
authors.initials: Z
authors.lastname: Li
authors.forename: Junhui
authors.initials: J
authors.lastname: Jia
authors.forename: Wenming
authors.initials: W
authors.lastname: Zhao
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D001169:Arthritis, Experimental / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D001842:Bone and Bones / Q000276:immunology / Q000473:pathology; D002460:Cell Line; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D053245:RANK Ligand / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D014612:Vaccines / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D053245:RANK Ligand; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D014612:Vaccines