designation of a novel dkk1 multiepitope dna vaccine and inhibition of bone loss in collagen-induced arthritic mice

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ID: 193531
2015
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Abstract
Dickkopf-1 (DKK1), a secretory inhibitor of canonical Wnt signaling, plays a critical role in certain bone loss diseases. Studies have shown that serum levels of DKK1 are significantly higher in rheumatoid arthritis (RA) patients and are correlated with the severity of the disease, which indicates the possibility that bone erosion in RA may be inhibited by neutralizing the biological activity of DKK1. In this study, we selected a panel of twelve peptides using the software DNASTAR 7.1 and screened high affinity and immunogenicity epitopes in vitro and in vivo assays. Furthermore, we optimized four B cell epitopes to design a novel DKK1 multiepitope DNA vaccine and evaluated its bone protective effects in collagen-induced arthritis (CIA), a mouse model of RA. High level expression of the designed vaccine was measured in supernatant of COS7 cells. In addition, intramuscular immunization of BALB/c mice with this vaccine was also highly expressed and sufficient to induce the production of long-term IgG, which neutralized natural DKK1 in vivo. Importantly, this vaccine significantly attenuated bone erosion in CIA mice compared with positive control mice. These results provide evidence for the development of a DNA vaccine targeted against DKK1 to attenuate bone erosion.
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zhang2015biomeddesignation Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors ;Xiaoqing Zhang;Sibo Liu;Shentao Li;Yuxuan Du;Yunpeng Dou;Zhanguo Li;Huihui Yuan;Wenming Zhao
Journal spectrochimica acta - part a: molecular and biomolecular spectroscopy
Year 2015
DOI
10.1155/2015/765490
URL
http://dx.doi.org/10.1155/2015/765490
Keywords
Medicine

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