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Therapeutic hepatitis B vaccine based on HBV PreS-S, C antigen and novel adjuvant CpG

A technology of hepatitis B surface antigen and hepatitis B core antigen, which is applied in the field of hepatitis B vaccine, can solve the problems of no treatment disease, no clear proposal for the transformation of anti-HBc antibody subtypes, etc.

Active Publication Date: 2015-09-02
JIANGSU THERAVAC BIO PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the patent does not clearly provide evidence for the subtype transformation of anti-HBc antibodies, and there is no direct evidence for the treatment of HBV infection and HBV-mediated diseases
[0009] Patent WO2007 / 031334 protects the components of hepatitis B therapeutic vaccine, which contains HBsAg, HBcAg and a saponin adjuvant, and CpG-ODN can be used as a common adjuvant. However, the hepatitis B therapeutic vaccine needs to be combined with nuclear Combined treatment with glucoside analogs can break through the immune tolerance of hepatitis B, and only 25% of e antigens are negative

Method used

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  • Therapeutic hepatitis B vaccine based on HBV PreS-S, C antigen and novel adjuvant CpG
  • Therapeutic hepatitis B vaccine based on HBV PreS-S, C antigen and novel adjuvant CpG
  • Therapeutic hepatitis B vaccine based on HBV PreS-S, C antigen and novel adjuvant CpG

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0079] Example 1. Hepatitis B surface antigen (HBsAg, S) and its precursor PreS2 are combined with hepatitis B core antigen (HBcAg) and CpG-ODN to enhance the immune response of hepatitis B surface antigen total IgG.

[0080] In order to detect the total IgG immune response of Hepatitis B surface antigen of the PreS2-S+HBcAg+CpG-ODN composition, the present inventors respectively used PreS2-S, HBcAg and CpG-ODN, HBsAg and CpG-ODG, HBsAg and Al(OH) 3 The adjuvant was mixed, and mice were immunized with the adjuvant. The HBsAg specific IgG level in the serum was measured and statistical analysis was performed to evaluate the relative HBsAg and CpG-ODG, HBsAg and Al(OH) 3 Combination, PreS2-S, HBcAg and CpG-ODN combined use on HBsAg total IgG immune response.

[0081] In this example, C57BL / 6 mice, female, 6-8 weeks old, were purchased from Shanghai Slack Company. The PreS2-S antigen used in this example was prepared by the inventors and is a natural PreS2-S expressed by Hansenula yeas...

Embodiment 2

[0085] Example 2. The combined use of hepatitis B surface antigen and its precursors PreS (PreS2-S), hepatitis B core antigen (HBcAg) and CpG-ODN at the level of humoral immunity enhances the hepatitis B surface antigen Th2 immune response.

[0086] According to the method described in Example 1, the effect of the PreS2-S+HBcAg+CpG-ODN composition of the present invention on the Th2 immune response of mice was determined. The difference is that the enzyme-labeled antibody used in the detection is horseradish peroxidation Enzyme-labeled goat anti-mouse IgG1 (purchased from SouthernBiotech, USA), the dilution factor is 1:20000. The results are shown in figure 2 in.

[0087] Antigen-specific immune responses are divided into two types, Th1 and Th2, and Th2 type responses correspond to high levels of antigen-specific IgG1 antibody titer. Al(OH) 3 It is a very strong Th2 vaccine adjuvant that can inhibit Th1 immune response, which is manifested by the induction of high levels of speci...

Embodiment 3

[0088] Example 3. The combined use of hepatitis B surface antigen and its precursor PreS (PreS2-S), hepatitis B core antigen (HBcAg) and CpG-ODN at the level of humoral immunity enhances the immune response of hepatitis B surface antigen Th1.

[0089] According to the method described in Example 1, the effect of the PreS2-S+HBcAg+CpG-ODN composition of the present invention on the Th1 immune response of mice was determined. The difference is that the enzyme-labeled antibody used in the detection is horseradish peroxidation Enzyme-labeled goat anti-mouse IgG2a (purchased from SouthernBiotech, USA), the dilution ratio is 1:6000. The results are shown in image 3 in.

[0090] As mentioned in Example 2, Al(OH) 3 It is a very strong Th2 vaccine adjuvant that can inhibit Th1 immune response, which is manifested by the induction of very low levels of specific IgG2a antibodies after immunization. CpG-ODG is a strong Th1 vaccine adjuvant, which can enhance Th1 immune response, which is exp...

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Abstract

The invention relates to a composition. The composition comprises (i) HBsAg and a precursor thereof (PreS-S), a fragment of the antigen, a variant of the antigen or a mixture of at least two of the HBsAg and the precursor thereof (PreS-S), the fragment and the variant; (ii) HBcAg1-X, a fragment of the antigen, a variant of the antigen or the fragment, or a mixture of at least two of HBcAg1-X, the fragment and the variant, wherein X is an integral number from 149-183; (iii) CpG-ODN, the oligonucleotide is full sulpho-modified, the sequence has two or more copies of 5'-NTCGTT-3' motifs and the length is 21 basic groups. The invention also relates to an application of the composition for treating the HBV infected and HBV mediated diseases, and a method for treating the HBV infected and HBV mediated diseases.

Description

Technical field [0001] The invention relates to a hepatitis B vaccine. In particular, the present invention relates to a therapeutic hepatitis B vaccine, which comprises hepatitis B surface antigen and its precursor PreS (PreS2-S), hepatitis B core antigen and thiooligodeoxynucleotides with immunostimulatory activity. Background technique [0002] Hepatitis B virus (HBV) infection is one of the serious public health problems worldwide. HBV infection is an important cause of chronic hepatitis B, cirrhosis and hepatocellular carcinoma (Fattovich G.J Hepatol 2008; 48: 335-352). Commonly used drugs for clinical treatment of chronic HBV infection mainly include nucleoside analogs and interferons. Nucleoside analogs cannot completely eliminate cccDNA in liver cells, and long-term use can easily lead to the emergence of resistant mutant strains and rebound after drug withdrawal (Kwon H, Lok AS. Nat Rev Gastroenterol Hepatol. 2011; 8: 275-284.) . Interferon is not suitable for asympt...

Claims

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Application Information

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IPC IPC(8): A61K39/295A61K39/29A61K39/39A61P31/20A61P1/16
Inventor 李建强葛君周童任苏林徐晓威孙莹孙洪林陈晓晓黄红颖顾月
Owner JIANGSU THERAVAC BIO PHARMA
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