title: Designation of a novel DKK1 multiepitope DNA vaccine and inhibition of bone loss in collagen-induced arthritic mice.
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.
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Capital Medical University, No. 10 Xitoutiao, You An Men, Fengtai, Beijing 100069, China ; Department of Immunology, College of Medical Sciences, China Medical University, No. 77 Puhe Road, Shenyang North Area, Shenyang, Liaoning 110122, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Capital Medical University, No. 10 Xitoutiao, You An Men, Fengtai, Beijing 100069, China.
authors.forename: Sibo
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Capital Medical University, No. 10 Xitoutiao, You An Men, Fengtai, Beijing 100069, China.
authors.forename: Shentao
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Capital Medical University, No. 10 Xitoutiao, You An Men, Fengtai, Beijing 100069, China.
authors.forename: Yuxuan
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Capital Medical University, No. 10 Xitoutiao, You An Men, Fengtai, Beijing 100069, China.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Dou
authors.affiliation: Department of Rheumatology & Immunology, Clinical Immunology Center, Peking University People's Hospital, No. 11 Xizhimen South Street, Beijing 100044, China.
authors.forename: Zhanguo
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Capital Medical University, No. 10 Xitoutiao, You An Men, Fengtai, Beijing 100069, China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Capital Medical University, No. 10 Xitoutiao, You An Men, Fengtai, Beijing 100069, China.
authors.forename: Wenming
authors.initials: W
authors.lastname: Zhao
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D001862:Bone Resorption / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D019556:COS Cells; D002522:Chlorocebus aethiops; D018985:Epitopes, B-Lymphocyte; D005260:Female; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D019444:Vaccines, DNA / Q000235:genetics / Q000494:pharmacology*
chemical_list: C501127:Dkk1 protein, mouse; D018985:Epitopes, B-Lymphocyte; D036341:Intercellular Signaling Peptides and Proteins; D019444:Vaccines, DNA