Connective tissue growth factor chimeric vaccine for treating liver fibrosis and application of connective tissue growth factor chimeric vaccine

A technology of chimeric vaccines and growth factors, applied in drug combinations, digestive system, antibody medical components, etc., to achieve the effect of stimulating liver cell proliferation and inhibiting liver cell apoptosis

Active Publication Date: 2015-07-01
THE FIRST AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XIAN JIAOTONG UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The N-terminal, C-terminal and MIR (major immunodominant region) regions of HBc can all be inserted into foreign short peptides and maintain the correct conformation to enhance its immunogenicity, but the immunogenicity of the MIR region is stronger

Method used

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  • Connective tissue growth factor chimeric vaccine for treating liver fibrosis and application of connective tissue growth factor chimeric vaccine
  • Connective tissue growth factor chimeric vaccine for treating liver fibrosis and application of connective tissue growth factor chimeric vaccine
  • Connective tissue growth factor chimeric vaccine for treating liver fibrosis and application of connective tissue growth factor chimeric vaccine

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Embodiment Construction

[0051] The invention provides a CTGF chimeric vaccine for treating liver fibrosis. The antigenic epitope of CTGF is successfully inserted into the c / e1B cell epitope of hepatitis B core antigen, and the CTGF chimeric vaccine that can be assembled into hepatitis B core-like particles is constructed. The amino acid sequence of the antigenic epitope of CTGF as shown in SEQ.ID.NO.1 is: SMDVRLPSPDCPFPRRVKLPGK. The vaccine can still stimulate the body to produce high-titer neutralizing antibodies against CTGF without the aid of an adjuvant. The degree of hepatic fibrosis induced by carbon tetrachloride was significantly reduced in the mice immunized with the vaccine. In further studies, we found that immunization with CTGF chimeric vaccine can significantly inhibit the activation of hepatic stellate cells in the liver of mice, and at the same time stimulate the proliferation of hepatocytes and inhibit the apoptosis of hepatocytes. In addition, the levels of TGF-β1 and PDGF in the m...

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Abstract

The invention discloses a CTGF (connective tissue growth factor) chimeric vaccine for treating liver fibrosis. The antigenic epitope of the CTGF is inserted into c/e1B cell epitope of hepatitis b virus core antigen to form the CTGF chimeric vaccine which can be assembled into hepatitis B core sample particles. Under the non-adjuvant assistance, the chimeric vaccine can stimulate a body to generate high-valence anti-CTGF neutral antibody. A mouse which is immunized by the chimeric vaccine is obviously relieved in fibrosis degree generated after carbon tetrachloride induction. According to the experimental verification, the CTGF chimeric vaccine can be used for obviously restraining the activation intensity of hepatic stellate cells in the mouse liver, and also can be used for stimulating liver cells to multiply and restraining liver apoptosis. Besides, the TGF-beta 1 and PDGF level in the immunized mouse is obviously reduced, so that the process of liver fibrosis can be relieved in a facilitated manner. According to the results, the CTGF chimeric vaccine can be used for successfully restraining the carbon-tetrachloride-induced mouse liver fibrosis. Therefore, the CTGF chimeric vaccine is expected to be developed into effective means for treating the liver fibrosis.

Description

technical field [0001] The invention belongs to the field of drugs for treating liver fibrosis, and in particular relates to a connective tissue growth factor chimeric vaccine for treating liver fibrosis and its application. Background technique [0002] Liver fibrosis (liver fibrosis) is the wound healing response of the liver to liver injury caused by various reasons, manifested as hyperplasia and deposition of connective tissue in the liver. Hepatic fibrosis is a necessary pathological process for the development of various chronic liver diseases to cirrhosis, and is one of the most important factors determining the prognosis of chronic liver diseases. At present, most chronic liver diseases lack effective etiological treatments, and studies have confirmed that liver fibrosis can continue to progress in some liver diseases after the etiology is removed, so the occurrence and development of liver fibrosis can be blocked or delayed, thereby preventing it from progressing to...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/29A61P1/16A61K39/00
Inventor 郝志明李爽吕颐菲张倩楠苏厚强霍涌玮田宏王丽蓉
Owner THE FIRST AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XIAN JIAOTONG UNIV
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