32 results about "Hepatitis b surface antigen" patented technology

The invention relates to the technical field of biological medicines, in particular to a vaccine for treating or preventing hepatitis B virus infection. The vaccine comprises a hepatitis B surface antigen and a composite adjuvant, wherein the composite adjuvant is prepared from CpG oligodeoxynucleotide and saponin QS-21, and the composite adjuvant is prepared from CpG oligodeoxynucleotide and saponin QS-21; the nucleotide sequence of the CpG oligodeoxynucleotide is as shown in SEQ ID NO. 1. According to the vaccine provided by the invention, an HBsAg antibody can be generated in a normal mouse body, and HBV in an HBV-carrier mouse can be effectively eliminated, so that the vaccine has the effect of treating or preventing hepatitis B virus infection. According to the vaccine provided by the invention, two adjuvants, namely CpG oligodeoxynucleotide and saponin QS-21, are adopted, so that the vaccine can be used for synergistically activating an immune effect, enhancing the activation of B cells and permanently transforming into plasma cells, and meanwhile, the vaccine can be used for resisting immune tolerance of T cells, realizing the removal of hepatitis B viruses and realizing functional cure of clinical hepatitis B treatment.

The invention discloses an application of a combination of entecavir, an ASO drug, an mRNA therapeutic vaccine and / or interferon in preparation of drugs for treating chronic hepatitis B. Entecavir and interferon have an antiviral effect, the ASO drug reduces hepatitis B surface antigen titer, and the mRNA therapeutic vaccine is high in immunization speed, so that the entecavir, ASO drug, mRNA therapeutic vaccine and / or interferon combination can inhibit virus replication, and can be used for treating chronic hepatitis B. The composition strikes hepatitis B virus from multiple angles and multiple levels, achieves a good, lasting and non-rebound antiviral effect, and can cure hepatitis B to a certain extent.

The invention belongs to the field of biological medicines, and particularly relates to an antigen-antibody compound for enhancing immune response of hepatitis B patients as well as a preparation method and application of the antigen-antibody compound. The antigen-antibody compound preparation prepared from the HBsAg and the anti-HBsAg monoclonal antibody is superior to an antigen-antibody compound preparation prepared from a polyclonal antibody in the aspect of continuously inducing the immune response of a chronic hepatitis B patient, and an antigen-antibody compound for inducing the immune response of the hepatitis B patient is developed for the first time; in the compound, the hepatitis B surface antigen is combined with the anti-HBsAg monoclonal antibody, and the compound formed by the hepatitis B surface antigen and the anti-HBsAg monoclonal antibody in a certain mass ratio can induce immune response of chronic hepatitis B patients and can also prevent and / or treat chronic hepatitis B.

Disclosed are antibodies to anti-hepatitis B surface antigen (HBsAg) (especially humanized antibodies), nucleic acid molecules encoding same, methods for preparing same, and pharmaceutical compositions containing same. The antibodies have higher affinity for HBsAg at neutral pH than at acidic pH, thereby significantly enhancing the virus clearance efficiency and prolonging the virus inhibition time. The antibodies and the pharmaceutical compositions can be used for preventing and / or treating HBV infections or diseases related to HBV infections (e.g., hepatitis B), for neutralizing the virulence of HBV in a subject (e.g., a human), for reducing the serum level of HBV DNA and / or HBsAg in the body of the subject, or for activating the humoral immune response of the subject (e.g., a chronic HBV infected or chronic hepatitis B patient) against HBV.

A preparation method for and the use of an aluminum hydroxide oxide nano-adjuvant based on calcium and silicon doping. The particle morphology of the AlOOH adjuvant is a 50-800 nm nano-particle, wherein silicon or calcium is doped in AlOOH crystal lattices, and the molar ratio of calcium or silicon to aluminum is 0.01-100:1. The preparation method comprises: synthesizing AlOOH by using an Al source, doping Ca or Si in a reaction solution by using a calcium source or a silicon source, precipitating Al(OH)3 and a dopant by adding an alkaline solution, and preparing a Ca- or Si-doped AlOOH adjuvant by means of a hydrothermal synthesis method. In a hepatitis B surface antigen and varicella-zoster virus glycoprotein E antigen model, the calcium- or silicon-doped AlOOH nano-adjuvant can simultaneously induce efficient humoral immunity and cellular immunity by means of in-vivo experiment verification of mice.

The present invention provides a multi-wavelength-based HBsAg detection method, including: detecting the light absorption value of a sample to be tested for HBsAg by a sandwich ELISA method using a multi-wavelength microplate reader to obtain the light absorption data of the sample to be tested for HBsAg at multiple wavelengths; determining the OD value of the sample, the OD value of the negative control, and the OD value of the positive control at dual wavelengths based on the light absorption data at wavelengths of 450 nm and 630 nm; determining whether the first detection result is valid within the preset concentration range of HBsAg based on the OD value of the negative control and the OD value of the positive control; if the first detection result is invalid within the preset concentration range of HBsAg, determining the second detection result of the sample to be tested for HBsAg based on the mapping relationship between the light absorption data at multiple wavelengths and the detection result of chemiluminescence method. The present invention improves the sensitivity, accuracy, and reliability of hepatitis B surface antigen detection at low concentrations.

The application discloses an LDH-based vaccine adjuvant and a preparation method and application thereof, and belongs to the technical field of aluminum adjuvant preparation of vaccines, and the preparation method comprises the following steps: mixing at least one of soluble magnesium salt, soluble zinc salt, soluble manganese salt and soluble calcium salt with soluble aluminum salt, and then performing a co-precipitation reaction with a sodium hydroxide aqueous solution in a colloid mill device, and performing crystallization to obtain LDH nanosheets; dispersing the LDH nanosheets in a PBS solution, adding a hepatitis B surface antigen molecule drug, uniformly mixing, and then performing centrifugation to obtain the LDH-based vaccine adjuvant. The LDH-based vaccine adjuvant can significantly promote the maturation of DC cells and the activation of T cells, and the total IgG level reflects the overall humoral immune response intensity of the body to vaccines or pathogens; the LDH-based vaccine adjuvant forms a "storage library" at an injection site to store antigens and slowly release the antigens, and the purpose of long-time continuous stimulation of the immune system in the body is achieved.

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.

The invention discloses a bipyrimidine heterocyclic compound and a preparation method and application thereof, the bipyrimidine heterocyclic compound has a structure as shown in a formula (I), and the invention also provides a pharmaceutical composition containing the compound or a stereoisomer, a medicinal salt, a hydrate, a solvate or a crystal thereof. The invention also discloses application of the compounds in preparation of drugs for treating hepatitis B virus infection, and particularly the compounds can be used as PAPD5 / 7 enzyme inhibitors and hepatitis B RNA non-stabilizers for treating hepatitis B viruses. The compound provided by the invention has the characteristics that the concentration of hepatitis B surface antigen and hepatitis B DNA and RNA can be remarkably reduced, and the probability of functional healing of hepatitis B can be remarkably improved by clinically combining with nucleoside drugs, oligonucleotide drugs / PD-L1 compounds and the like.

Provided are affinity ligands that bind to Hepatitis B surface antigen (HBsAg), affinity resins comprising the HBsAg-binding ligands, and related compositions and methods for the isolation and / or purification of HBsAg.

The invention relates to a composition comprising a polypeptide comprising, or consisting of, the amino acid sequence of SEQ ID) NO: 1, or a sequence having at least 80%, 85%, 90%, 95%, 98%, or 99% sequence identity to SEQ ID NO: 1 (R21), wherein said polypeptide is in the form of a virus-like particle (VLP), wherein said particle comprises less than 10% free hepatitis B surface antigen protein, for use in the immunisation of a human subject susceptible to Plasmodium falciparum infection, characterised in that said composition is administered in a dosage regimen of at least one dose of 1 μg to 20 μg R21 per administration for a subject at least 18 years old, or at least one dose of 0.5 μg to 10 μg R21 per administration for a subject less than 18 years old. The invention also relates to kits, methods and uses.

This invention belongs to the field of affinity membrane and bioseparation technology, and provides a cellulose-based affinity membrane for hepatitis B virus (HBV), its preparation method, and its application. The affinity membrane consists of a base membrane and an affinity ligand immobilized on the base membrane. The base membrane is a carboxylated cellulose filter membrane or a carboxylated modified cellulose filter membrane. The affinity ligand is a biomolecule that specifically recognizes HBV surface antigen. The carboxyl groups of the base membrane and the amino groups of the affinity ligand are linked by amide bonds. Unreacted carboxyl groups on the base membrane are blocked by a blocking reagent. The carboxyl content of the base membrane is 400-1000 μmol / g, the pore size is 400-1000 nm, and the porosity is 30%-60%. The application refers to the use of the above-mentioned affinity membrane in the specific clearance of HBV from HBV-positive plasma. This invention can achieve efficient and specific clearance of HBV from plasma, maximally preserving the activity and function of normal plasma components, and improving the feasibility of industrial application.

A combination comprising a tricycle compound and use thereof in the preparation of a medicament for treating HBV. The combination is a combination of a compound of formula (I) or a pharmaceutically acceptable salt thereof and any one drug in the following groups a-c: a. a hepatitis B surface antigen inhibitor, b. a reverse transcriptase inhibitor, and c. a hepatitis B surface antigen inhibitor and a reverse transcriptase inhibitor.

The present invention relates to: a conjugate in which a receptor-binding domain (RBD) of coronavirus and a hepatitis B surface antigen (HBsAg) are linked; virus-like particles including the conjugate; and a coronavirus vaccine composition containing the conjugate and / or virus-like particles.

The invention provides application of a BTLA inhibitor in preparation of a medicine for preventing and / or treating chronic hepatitis B, and belongs to the technical field of biological medicine. Research finds that antagonistic B and T lymphocyte attenuation factors (BTLA) can promote removal of hepatitis B surface antigen (HBsAg), reduce the expression level of HBeAg, promote activation and proliferation of T cells and enhance host immune response, so that the purpose of preventing and / or treating chronic hepatitis B is achieved, and functional cure of chronic hepatitis B (CHB) is achieved. The invention provides more choices for medicines for clinically preventing and / or treating chronic hepatitis B.

The application belongs to the technical field of pharmaceutical chemistry, and discloses a compound for inhibiting hepatitis B surface antigen and application thereof. It is proved through research that the recombinant plasmid S-HiBiT constructed can characterize the expression and secretion of HBs, and can be used for screening the compound for inhibiting HBs, and a cell model for screening anti-HBV drugs targeting HBsAg, i.e. HepG2-PB-S-HiBiT stable expression cell line. It is verified through experiments that the model is particularly suitable for high-throughput screening of compounds. Compound 1 and compound 3 capable of inhibiting HBsAg are found through screening of a compound library by using the model, the drug has the potential to be further developed into a hepatitis B treatment candidate drug, and a new drug is provided for the treatment of hepatitis B.

An oral vaccine for Hepatitis B is disclosed. The oral vaccine for Hepatitis B includes a delivery platform including Arthrospira platensis with a plurality of host genomes and a plurality of Hepatitis B surface antigen delivery vectors coupled to the plurality of host genomes. Each Hepatitis B surface antigen delivery vector of the plurality of Hepatitis B surface antigen delivery vectors has a nucleotide sequence identical to nucleotide sequence of SEQ ID NO. 2. Each respective Hepatitis B surface antigen delivery vector of the plurality of Hepatitis B surface antigen delivery vectors includes at least one surface antigen of Hepatitis B with a weight ratio of the delivery platform to the at least one surface antigen of Hepatitis B in a range of 1: 10-4 to 1: 2x10- 3 (delivery platform: at least one surface antigen of Hepatitis B).

The present invention provides a multi-wavelength-based HBsAg detection method, including: detecting the optical absorption value of a sample to be detected for HBsAg by a sandwich immunoassay using a multi-wavelength microplate reader to obtain the optical absorption data of the sample to be detected for HBsAg at multiple wavelengths; determining the OD value of the sample, the OD value of the negative control, and the OD value of the positive control at two wavelengths based on the optical absorption data at 450 nm and 630 nm wavelengths; determining whether the first detection result is valid within the preset concentration range of HBsAg based on the OD value of the negative control and the OD value of the positive control; if the first detection result is invalid within the preset concentration range of HBsAg, determining the second detection result of the sample to be detected for HBsAg based on the mapping relationship between the optical absorption data at multiple wavelengths and the detection result of chemiluminescence method. The present invention improves the sensitivity, accuracy, and reliability of the detection of hepatitis B surface antigen at low concentrations.

The application discloses a hepatitis B surface antigen specific B cell receptor gene knock-in mouse model, and establishes a hepatitis B virus surface antigen (HBsAg) specific B cell receptor (BCR) gene knock-in mouse model, wherein 70-90% of B cells of the mouse can specifically recognize HBsAg, and differentiate into germinal center B cells and plasma cells. Therefore, the model can be used for basic research on hepatitis B antiviral humoral immune response and tolerance mechanism, and can also be used for application research on development of drugs and vaccines for breaking HBsAg immune tolerance. In summary, the establishment of the model lays a solid foundation for development of a functional cure immune means for hepatitis B.

There is provided a method of curing chronic hepatitis B infection in a human, the method comprising administering to a subject in need thereof an effective amount of one or both of an exogenous anti-HBs antibody or an anti-HBs antibody producing carrier, the present invention relates to a method for reducing cellular and blood hepatitis B surface antigen (HBsAg) by providing continuously increased levels of anti-HBs antibodies in the subject.

The present application relates to the technical field of immunological detection, in particular to hepatitis B PreS1 antigen and its preparation method and application. The present application first selects an active PreS1 polypeptide sequence, which is coupled to a hepatitis B surface antigen HBsAg molecule through a crosslinking agent to obtain a hepatitis B PreS1 antigen having both hepatitis B surface antigen activity and PreS1 antigen activity, which can be used as a calibrator and positive control in a hepatitis B PreS1 antigen detection kit. The kit uses anti-PreS1 antibody as coating and anti-HBsAg antibody as enzyme label. The artificial coupled hepatitis B PreS1 antigen prepared by the present application can effectively replace the currently used PreS1 real positive sample on the market, has no biological safety risk, stable source, and various indexes such as reactivity, vehicle stability and thermal stability, which are all better than those of the real positive sample, and has high innovation and applicability.

There is provided a method of treating chronic hepatitis B infection (CHB) and / or chronic hepatitis D infection (CHD) in a human, comprising the steps of:a) administering to the human a composition comprising an antisense oligonucleotide (ASO) 10 to 30 nucleosides in length, targeted to a HBV nucleic acid (an HBV ASO);b) administering to the human a composition comprising a replication-defective chimpanzee adenoviral (ChAd) vector comprising a polynucleotide encoding a hepatitis B surface antigen (HBs) and a nucleic acid encoding a hepatitis B virus core antigen (HBc);c) administering to the human a composition comprising a Modified Vaccinia Virus Ankara (MVA) vector comprising a polynucleotide encoding a hepatitis B surface antigen (HBs) and a nucleic acid encoding a hepatitis B virus core antigen (HBc); andd) administering to the human a composition comprising a recombinant hepatitis B surface antigen (HBs), recombinant hepatitis B virus core antigen (HBc) and an adjuvant.

The invention discloses a nano antibody targeting a hepatitis B surface antigen and application of the nano antibody. The nano antibody has an amino acid sequence as shown in SEQ ID NO: 1-5, and has high affinity to HBsAg. The nano antibody not only can effectively neutralize hepatitis B virus, but also can enter cells to realize'multi-link and all-directional 'inhibition of virus life cycle, including inhibition of virus RNA transcription, protein expression, nucleocapsid assembly, DNA replication and particle secretion, and can significantly down-regulate HNF4alpha, Sp1 and other key transcription factors in host hepatocytes. The antibody can be efficiently expressed in a prokaryotic or eukaryotic system. The PEGylated derivative (such as Nb1-PEG40) can prolong the half-life period, and shows stronger effects of clearing serum HBsAg and inhibiting liver virus replication in an HBV infected mouse model. The invention provides a new strategy and drug candidate for hepatitis B treatment.

This invention discloses a non-invasive systemic assessment method and system for predicting the transformation of follicular lymphoma. The method includes the following steps: S1, obtaining four characteristics of the subject: peripheral blood hepatitis B surface antigen (HBsAg), neutrophil-to-lymphocyte ratio (NLR), serum lactate dehydrogenase (LDH), and PET-CT reporting maximum standardized uptake (SUVmax); S2, determining the weight of each characteristic based on its importance, with the weights from high to low being HBsAg, LDH, NLR, and SUVmax, and converting each characteristic into a risk score of 0-3 points using a unique fixed node; S3, weighted summing of the scores of the four characteristics to obtain a total score S, establishing a correspondence between the total score and transformation, constructing a web-based calculator and transformation scoring system, and outputting the individual transformation probability prediction result. By embedding the four conventional indicators (HBsAg, NLR, LDH, and SUVmax) selected by LASSO and Boruta into a lightweight CatBoost model, the transformation probability can be output, realizing a non-invasive assessment of the histological transformation risk of follicular lymphoma at initial diagnosis.

The invention provides a bispecific antibody specifically combined with hepatitis B surface antigen and application thereof, and belongs to the technical field of chronic hepatitis B treatment and prevention. The bispecific antibody specifically bound with the hepatitis B surface antigen comprises a first antibody, and the first antibody is obtained by connecting a humanized anti-HBsAg antibody 2H5 heavy chain variable region and a light chain variable region with a human IgG1 heavy chain constant region and a light chain constant region respectively and mutating an Fc segment of the human IgG1 heavy chain constant region; the second antibody is obtained by connecting the 125S heavy chain variable region of the humanized anti-HBsAg antibody with the Fc segment of the heavy chain constant region of the human IgG1 and mutating the Fc segment of the heavy chain constant region of the human IgG1. The bispecific antibody is combined with two virus epitopes at the same time, so that immune escape is avoided; the neutralizing capability on viruses and the killing capability on infected cells are enhanced, and the two are cooperated to eliminate infection.

The present invention relates to the field of antibody drug technology, particularly to antibodies against hepatitis B surface antigen (HBsAg), their applications, and detection kits. Disclosed are a monoclonal antibody and its sequence, which binds to an epitope located within the highly hydrophilic domains 117-134 of the HBsAg. The antibodies of the present invention can be used for medical treatment and diagnosis, for example, in the treatment and / or diagnosis of liver diseases caused by the HBV, such as acute and chronic hepatitis, cirrhosis, and primary liver cancer, and have promising clinical application prospects.

Provided are an antigen-antibody complex vaccine for enhancing an immune response in a chronic hepatitis B patient and a preparation method therefor. Specifically, provided is an antigen-antibody complex for inducing an immune response in a chronic hepatitis B patient. The complex comprises a hepatitis B surface antigen and an anti-HBsAg monoclonal antibody, wherein the hepatitis B surface antigen binds to the anti-HBsAg monoclonal antibody. The complex can induce the immune response in the chronic hepatitis B patient, and can also prevent and / or treat chronic hepatitis B.

The present invention belongs to the field of biopharmaceutics and in particular relates to a pharmaceutical composition. The pharmaceutical composition comprises a hepatitis B surface antigen, a hepatitis B core antigen, and an immunostimulatory composition, wherein the immunostimuilatory composition comprises a saponin and a CpG oligodeoxynucleotide, or consists of an adjuvant comprising a saponin and a CpG oligodeoxynucleotide.

The invention discloses a purification and separation device for gradient centrifugal screening of hepatitis B surface antigens. The purification and separation device comprises a probe, an electromagnet, a U-shaped strip plate and a porous hose. The device and the method have the beneficial effects that the layered liquid in the tubular container can be shot and collected, gradient layered lines and the like can be quickly distinguished and found out, the tedious step that micro-observation can be carried out after separation and taking-out is omitted, and the recovery rate of target substances is increased; the rotatable electromagnet is used for following the metal wafer in the tubular container according to the adjustment and change of the magnetic field intensity, so that adjustment according to different observation requirements can be met; the two connected displacement probes are respectively arranged at a high point and a low point of the layered liquid by rotating the probe cylinder, so that the thickness of the layered liquid can be obtained by virtue of the sum of displacement variations at the high point and the low point, and calculation data is provided for subsequently obtaining the weight or volume of the layered liquid; the device has the function of adjusting the distance between the camera and a to-be-observed part, and solves the problem that effective observation cannot be conveniently implemented due to the small internal space of a tubular container.

The invention belongs to the technical field of biological detection, and particularly relates to a detection kit and a detection method for anti-hepatitis B virus ADCP activity of human immune globulin. According to the detection method disclosed by the invention, a PLC / PRF / 5 cell for expressing a human hepatitis B surface antigen (HBsAg) is taken as a target cell, a THP-1 cell modified by genetic engineering is taken as an effector cell, and ADCP activity detection of anti-hepatitis B virus of human immunoglobulin is realized by adopting a reporter gene method. Wherein the transformed THP-1 cell THP-1-NF-kB naturally expresses CD32a (Fc [gamma] RIIa) and CD64a (Fc [gamma] RIa), and a human leukemia mononuclear cell of an NF-kB-Luc luciferase reporter gene is stably transformed. The detection method has the advantages of simple operation, high precision and accuracy and the like, and provides important technical support for research and development of antibody drugs.