21 results about "HBcAg" patented technology

The present invention provides use of a reagent for improving RAB11A expression in preparing a drug for treating hepatitis B, belonging to the field of biomedicine. The present invention verifies through experiments that overexpression of RAB11A can significantly reduce the levels of secreted HBsAg and HBcAg, significantly inhibit HBV replication, provides a new potential target for treating hepatitis B, provides more effective treatment options for clinical treatment, and has broad application prospects and market potential.

The present invention relates to the use of ciprofibrate in the preparation of a drug for anti-hepatitis B virus, belonging to the field of biomedical technology. The present invention provides the use of ciprofibrate in the preparation of a drug for anti-hepatitis B virus. Ciprofibrate reduces the expression levels of hepatitis B surface antigen HBsAg, hepatitis B e antigen HBeAg, and hepatitis B core antigen HBcAg in human primary cells infected with hepatitis B virus, inhibits hepatitis B virus from infecting cells, inhibits the proliferation and replication of hepatitis B virus, can protect neonatal hepatocytes from being reinfected, has an anti-hepatitis B virus effect, and thus prevents and treats diseases caused by hepatitis B virus. Ciprofibrate, as a lipid-regulating drug, has minor side effects, does not require subcutaneous injection, and has high patient compliance.

In the field of Hepatitis B virus (HBV) detection, disclosed are a method for detecting HBcAg by means of using a double antibody sandwich method, and an antibody and kit for detecting HBcAg; also included is a monoclonal antibody that can be used in the immunological detection of HBcAg in a tissue or cell sample.

Provided herein are methods of treating hepatitis B and / or hepatitis D using a Na + / taurocholic acid co-transporter polypeptide (NTCP) inhibitor (e.g., a compound of Formula (I) or a pharmaceutically acceptable salt thereof, or a compound of Formula (II) or a pharmaceutically acceptable salt thereof). Such methods may include reducing the concentration of hepatitis B DNA, reducing the concentration of hepatitis D DNA, reducing hepatitis B surface antigen, and reducing hepatitis B core antigen (HBcAg).

The application discloses a recombinant oncolytic virus rVSV M51R The application of C in hepatitis B liver cancer belongs to the field of biological medicine. The recombinant oncolytic virus is a recombinant attenuated vesicular stomatitis virus carrying an HBV HBcAg gene and having an M-R mutation at the 51st amino acid of the M gene. The recombinant oncolytic virus is proved to have a curative effect in a tumor model, and can be used for preparing a therapeutic vaccine for HBV-positive liver cancer, HBV-positive diffuse large B-cell lymphoma and other HBV-positive tumors.

The present invention belongs to the field of biochemical technology, and specifically discloses a hepatitis B core antigen single-chain antibody phage library and its construction and application. The present invention successfully amplifies VH and VL fragments by designing HBcAg single-chain antibody heavy chain variable region primers (VH) and light chain variable region primers (VL), and uses the amplified VH and VL fragments and the designed HBcAg single-chain antibody full-length primers to amplify and splice to obtain scFv DNA fragments. On this basis, phage library technology is used to successfully construct a HBcAg single-chain antibody library, and HBcAg single-chain antibodies with high specificity and high sensitivity are screened therefrom, and an HBcAg precise quantitative kit can be further developed based on this. The technology provided by the present invention is of great significance to the clinical detection of HBcAg.

The application provides a kind of anti-hepatitis B HBcAg monoclonal antibody and its application and product, it is related to the field of biotechnology.The application uses HBcAg to immunize Balb / c mouse, takes mouse spleen cell and fuses with myeloma cell, and obtains hybridoma cell with high specificity by specific high-throughput screening, obtains a large number of mouse ascites by culture and re-immunization, and then obtains high-purity, high-sensitivity and high-specificity anti-HBcAg monoclonal antibody by multi-step separation and purification, which provides the required raw material for developing HBcAg detection immunostrip.The anti-HBcAg monoclonal antibody of the application can be used for immunological detection such as immunoblotting and immunofluorescence, and the obtained antibody has good specific binding capacity.

The invention discloses a nano antibody targeting a hepatitis B core antigen as well as a coding gene and application thereof, and relates to the technical field of biological medicines. The nano antibody comprises an amino acid sequence as shown in any one of SEQ ID NO: 1 to SEQ ID NO: 5, and can be specifically combined with HBcAg. The invention also relates to a coding nucleic acid, an expression vector, a host cell and a preparation method of the nano antibody, and application of the nano antibody in preparation of anti-hepatitis B virus drugs and diagnostic reagents. Experiments show that the nano antibody has high affinity of targeting HBcAg, can combine and destroy hepatitis B virus nucleocapsid assembly and inhibit secretion of virus proteins such as HBsAg, HBeAg and the like, and thus has good anti-hepatitis B virus activity.

The invention relates to methods of vaccination, comprising administering to a human subject a first dose of an HBcAg particle, an HBsAg, and c-di-AMP; a second dose of the HBcAg particle, the HBsAg, and c-di-AMP; and a dose of a vaccine vector. The invention also relates pharmaceutical compositions, combinations of HBcAg particles, HBsAg and c-di-AMP, and kits for use in said methods.

The invention belongs to the technical field of cellular immunity, and particularly relates to a DC-CIK cell culture method based on an HBV protective antibody positive healthy donor and application, the cell culture method comprises the following steps: selecting HBsAg negative and anti-HBs antibody positive healthy donor peripheral blood mononuclear cells, loading a dendritic cell (DC) by using a mixed antigen of HBcAg and HBsAg, and culturing the DC-CIK cell by using a cell culture medium. And co-culturing the DC cells and cytokine-induced killer cells (CIK) to finally obtain the allogenic DC-CIK cells. According to the invention, DC cells of healthy donors and CIK cells are co-cultured to obtain allogenic DC-CIK cells, an HBcAg and HBsAg mixed antigen loading technology is adopted to significantly improve the antigen presentation capability of the DC cells, an optimized culture system enhances the targeting killing function of the cells, and the HBsAg clearance rate and the cccDNA inhibition rate can be effectively improved in combination with nucleoside analogue treatment, so that the DC-CIK cells can be used for preparing the DC-CIK cells. The synergistic breakthrough of efficient virus removal, immune function reconstruction and low recurrence rate in hepatitis B treatment is realized.

The invention discloses a fully humanized antibody aiming at HBcAg protein expressed by hepatitis B related liver cancer cells. The antibody is proved to be capable of killing tumor cells of hepatitis B related liver cancer in in-vivo and in-vitro experiments, and the treatment effect of the PD-1 monoclonal antibody can be improved. The antibody provided by the invention has the characteristic of high-specificity recognition of hepatitis B related liver cancer tumor cells, can kill few para-carcinoma hepatocytes, and has better safety. The antibody provided by the invention can be used as a therapeutic drug for patients with advanced hepatitis B related liver cancer and a combined drug for immune checkpoint inhibitor treatment, can also be combined with an immune checkpoint inhibitor to be used as a new adjuvant and / or adjuvant therapy drug for patients with hepatitis B related liver cancer in the perioperative period, and has important value.

The present disclosure provides a photo-activated chemiluminescence detection kit and method for detecting hepatitis B virus core IgM type antibody. The detection kit comprises: reagent 1, luminescent microspheres coated with hepatitis B core antigen (HBcAg), which can react with singlet oxygen and generate a detectable light signal; reagent 2, anti-IgM antibody labeled with a first partner; and reagent 3, blocking reagent, which can reduce or eliminate interfering antibodies. The detection kit of the present disclosure destroys the structure of interfering antibodies by chemical and / or biological methods, thereby weakening or even eliminating the signal or shielded signal caused by interfering antibodies, which can significantly improve the accuracy of hepatitis B virus core IgM type antibody detection.

The invention discloses a hepatitis B virus HBcrAg detection kit, which comprises an immunomagnetic bead working solution, a sample treatment solution and an HBcrAg labeling working solution, the immunomagnetic bead working solution comprises immunomagnetic beads coated with a coating antibody and a magnetic bead diluent; the sample treatment liquid is used for removing outer membranes of hepatitis B virus particles under mild conditions and dissociating hepatitis B virus core particles to release HBcrAg; the HBcrAg marking working solution comprises a marking antibody coupled with a marker and a marker diluent. The detection kit can effectively split the hepatitis B virus core particles under mild conditions, and can capture the hepatitis B virus core particles so as to avoid interference of endogenous antibodies, so that the content of HBcrAg in a sample is more accurately detected, the HBcAg index is measured, the traditional defect of two-in-half hepatitis B is made up, and the detection kit can be used for detecting the HBcrAg content of the sample and detecting the HBcrAg index. And iteration from'two pairs of hepatitis B 'to'three pairs of hepatitis B' is realized. The invention further discloses an HBcrAg detection method adopting the HBcrAg detection kit for the hepatitis B virus.

The present invention belongs to the technical field of medical detection, and specifically discloses a hepatitis B virus particle lysate and its preparation and application. The lysate comprises the following components in parts by weight: 10-20 parts of thiourea, 70-90 parts of urea, 8-12 parts of sodium dodecyl sarcosinate, 3-5 parts of Tween, 4-8 parts of CHAPS, 1-3 parts of TCEP, 3-5 parts of Triton X-100, 8-12 parts of glycerol, 1-3 parts of Tirs-HCl, and 0-100 parts of deionized water. The lysate provided by the present invention can expose HBcAg in hepatitis B virus particles and has little influence on detection antibodies.

Provided herein are compositions of CD1280 binding proteins and a Hepatitis B virus core antigen (HBcAg) and / or a Hepatitis B virus E antigen (HBeAg), or antigenic fragments or mutants thereof, attached to the CD180 binding protein, and methods for using the compositions to treat or limit the development of hepatitis-B virus (HBV)-related disorders.

The invention provides a construction method of a two-person-derived hepatitis B mouse model characterized by T cell immune reconstruction. The method is characterized by promoting the reconstruction of humanized T cells and comprises the steps of constructing a human liver chimeric immunodeficiency mouse model, infecting the human liver chimeric immunodeficiency mouse with HBV, implanting human immune cells and the like, and results show that hAlb, HBV DNA and HBsAg can be continuously detected in blood of the constructed mouse, HBsAg and HBcAg can be detected in the liver, and the human liver chimeric immunodeficiency mouse can be used for detecting HBcAg. Human-derived immune cell infiltration mainly comprising CD3 + T cells can be detected in organs such as blood and liver, so that a hepatitis B mouse model with double-derived liver and immune systems is formed. The technology for constructing the humanized mouse model can be used for researching the interaction mechanism of the HBV and the immune cells in the hepatitis B progress, and the technical scheme provides a good animal model for researching the hepatitis B progress, the immune cell depletion mechanism, clinical hepatitis B drug treatment and the like.

The present application relates to the technical field of antibody drugs, and particularly relates to a binding molecule against hepatitis B virus core antigen HBcAg and application thereof. The binding molecule provided by the present application comprises at least one immunoglobulin single variable domain, and the amino acid sequences of CDR1, CDR2 and CDR3 in the immunoglobulin single variable domain are respectively shown as SEQ ID NO:1, SEQ ID NO:2 and SEQ ID NO:3. The binding molecule against hepatitis B virus core antigen provided by the present application can reduce the levels of HBcAg, HBeAg, HBsAg and HBV DNA, and can also reduce the assembly of infectious hepatitis B virus particles, block the secretion of infectious hepatitis B virus complete particles, inhibit the infection and amplification of hepatitis B virus, and has a significant therapeutic effect on hepatitis B.

The application discloses a mouse model of HBV-specific exhausted CD8+ T cells and application thereof. First, C57 mice of CD45.1 type are immunized by using HBsAg and HBcAg antigen peptides of HBV to obtain mice with HBV-specific immunity; C57 mice of CD45.2 type with liver-specific expression of HBV transgene are subjected to X-ray myeloablation; bone marrow of the CD45.1 type mice with HBV-specific immunity is collected, and the myeloablated CD45.2 type mice are transplanted through the orbital vein; after transplantation, flow cytometry is used to detect HBV-specific CD8+ T cells and exhaustion-related phenotypes, and establishment of the mouse model of HBV-specific exhausted T cells is confirmed. The mouse model has a high level of HBV-specific CD8+ T cells, and the exhaustion phenotype is significant, and can be applied to the formation mechanism of hepatitis B T cell exhaustion and research on related new targets and new strategies for diagnosis and treatment.

The application provides a method for constructing a double humanized hepatitis B mouse model characterized by T cell immune reconstruction. The method is characterized by promoting humanized T cell reconstruction, and comprises the steps of constructing a human liver chimeric immunodeficient mouse model, infecting the human liver chimeric immunodeficient mouse with HBV, and implanting human immune cells. The results show that hAlb, HBV DNA and HBsAg can be continuously detected in the blood of the constructed mouse, HBsAg and HBcAg can be detected in the liver, and human immune cell infiltration mainly in the form of CD3+ T cells can be detected in the blood, liver and other organs, thereby forming a double humanized hepatitis B mouse model of the liver and the immune system. The humanized mouse model construction technology of the application can be used to study the interaction mechanism of HBV and immune cells in the process of hepatitis B. The technical scheme provides a good animal model for the research of hepatitis B progression, immune cell exhaustion mechanism and clinical hepatitis B drug treatment.

The present invention provides methods and compositions for the treatment of HBV. Disclosed is an HBcAg particle comprising HBV core proteins from at least two different HBV genotypes and a vaccine vector comprising a nucleotide sequence having > = 90% sequence identity to SEQ ID NO: 5. Corresponding pharmaceutical compositions and their use in therapy, in drug preparation and in methods of vaccination are disclosed. The vaccination method comprises administering to a human (i) a first dose and (ii) a second dose of HBcAg particles and HBsAg, and (iii) a dose of a vaccine vector that expresses HBsAg from HBV genotype A, HBcAg from HBV genotype D, HBsAg having > = 90% sequence identity to SEQ ID NO: 7, HBcAg having > = 90% sequence identity to SEQ ID NO: 8 or 17, and an RT domain having > = 90% sequence identity to SEQ ID NO: 9.

The invention provides a circRNA vaccine expressed by multiple antigens and a preparation method of the circRNA vaccine, and belongs to the technical field of biological medicines, and the circRNA vaccine comprises a circular RNA (circRNA) sequence capable of simultaneously expressing two or more antigen sequences. The circRNA vaccine provided by the invention can be used for simultaneously expressing any two or three of HBV antigens HBsAg and HBcAg and therapeutic polypeptide, and also can be used for expressing a corresponding RSV (Respiratory Syndrome Virus) trimer F antigen. The circRNA vaccine for mammal injection is obtained through in-vitro gene synthesis, in-vitro transcription reaction, linear RNA (Ribonucleic Acid) cyclization, hydrogel / amino acid nanoparticle preparation and the like. HBVamp can be reduced for healthy people; the traditional Chinese medicine composition can be used for relieving and eliminating the symptoms, stabilizing the illness state, reducing the virus transmission, reducing the dosage, shortening the treatment course, delaying / reversing the disease course and improving the prognosis and life quality aiming at infected persons, and can be used for relieving and eliminating the symptoms, stabilizing the illness state, reducing the virus transmission, reducing the dosage, shortening the treatment course and improving the prognosis and life quality.