263results about "Reverse transcribing DNA viruses" patented technology

To provide methods for treating a subject having or at risk of developing a neurocognitive disorder, such as frontotemporal lobar degeneration or neuronal ceroid lipofuscinosis.SOLUTION: Provided is a method comprising administering, to a subject diagnosed as having a neurocognitive disorder (NCD), a composition comprising a population of cells comprising a transgene encoding a progranulin (PGRN) or a granulin (GRN).SELECTED DRAWING: Figure 1A

The invention provides an immunologic adjuvant composition as well as a preparation method and application thereof. The immunologic adjuvant composition comprises an immunologic active agent and a liposome for loading the immunologic active agent, wherein the immunologic active agent comprises saponin and CpG oligodeoxynucleotide. The immunologic adjuvant composition can induce immune response of mammals to human herpes virus and / or hepatitis B virus, and can induce generation of a relatively high cellular immune response level. The QS21 and the CpG oligodeoxynucleotide are simultaneously loaded by using the liposome, so that the QS21 and the CpG oligodeoxynucleotide have a better synergistic effect in the aspect of promoting cellular immunity, and compared with a Shingrix commercially available vaccine, the vaccine can induce generation of a higher cellular immune response level.

The present invention relates to a viral gene therapy vector for removing hepatitis B viruses, a preparation method therefor, and the use thereof, aiming to solve the problem in which existing viral gene therapy vectors can only inhibit the replication of hepatitis B viruses, but cannot remove virus cccDNA. The vector comprises a promoter, an intron, an enhancer, a nuclear localization signal (NLS) functional domain encoding gene of PGLYRP2 protein, an HBV DNA binding domain encoding gene of the PGLYRP2 protein, a secretory signal peptide functional domain encoding gene of the PGLYRP2 protein, an HBV nucleocapsid-binding functional domain encoding gene of the PGLYRP2 protein, and an IRES fragment. The viral gene therapy vector can remarkably promote the removal of HBVs in the liver of mice and is used for treatment of hepatitis B virus infection.

Provided herein are non-naturally occurring variants of the hepatitis B virus (HBV) Core protein, the HBV polymerase N-terminal domain, and the HBV polymerase C-terminal domain, as well as immunogenic fragments thereof. Fusion proteins comprising the HBV variants fused to a herpes simplex virus (HSV) glycoprotein (gD) sequence, as well as methods of using the fusion proteins, are also provided.

Disclosed herein are alphavirus vectors that include neoantigen-encoding nucleic acid sequences derived from a tumor of a subject. Also disclosed are nucleotides, cells, and methods associated with the vectors including their use as vaccines.

The present invention provides a tumor neoantigen vaccine system specifically marking a heterologous protein, and a use thereof. The vaccine system is composed of a heterologous protein mRNA vaccine and a recombinant oncolytic virus; the heterologous protein mRNA vaccine is used to induce an organism to generate heterologous protein-specific memory T cells, and the recombinant oncolytic virus is used to promote a tumor to express microorganism-derived tumor neoantigens. When pre-immunized memory T cells detect these marked specific neoantigens, the tumor expressing the neoantigens is quickly activated and killed, the release of tumor autoantigens is promoted, dendritic cells phagocytize antigens to further initiate an anti-tumor response, and a systemic anti-tumor immune effect is activated by means of antigenic epitope spreading.

The invention belongs to the technical field of tumor vaccines, and particularly relates to an mRNA (messenger Ribonucleic Acid) vaccine for coding tumor antigen epitopes as well as a preparation method and application thereof. In order to overcome the defect of immune escape caused by insufficiency or loss of a single antigen, the invention provides an mRNA vaccine capable of simultaneously coding a plurality of tumor antigen epitopes, and the tumor antigen epitopes are selected from high-frequency mutation epitopes of human tumor driving genes, such as G12D, G12V and G12C mutations of RAS genes; the antigenic epitopes can be used for preparing antigenic epitopes related to common viruses of human tumors, such as HPV16E6 / E7, EBV LAMP1 or CMV pp65, and tumor high-expression carcino-embryonic antigen gene epitopes, such as MAGE-A4, NY-ESO-1, WT1, and the like. The mRNA vaccine is obtained by serially expressing a plurality of tumor antigen epitopes and encapsulating and delivering lipid nanoparticles. Experiments prove that the compound can effectively prevent and treat various tumors and has a wide application prospect.

The invention discloses a virus-like structure nano adapter and application thereof, on the basis of hepatitis B virus core protein Uniprot P03146 of which nucleic acid binding domains at 145-183 sites of a C tail end are removed, CBP as shown in SEQ ID NO.01 is respectively inserted into a spike part and an N tail end of the hepatitis B virus core protein Uniprot P03146. The invention is constructed based on collagen combined polypeptide CBP designed by bionic decorrin, aims to imitate the interaction between natural decorrin and collagenous fiber, can efficiently cross over corneal epithelium barrier and repair corneal stroma in a non-photo-crosslinking manner, and solves the limitation of existing clinical treatment.

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 present invention provides methods and compositions for the stimulation of immune responses and for treating or preventing allergic disease and responses and inflammatory disease and responses. In particular, the present invention provides nanoemulsion compositions and methods of using the same for the induction of immune responses that prevent or treat allergic disease by reducing allergic response. Compositions and methods of the invention find use in, among other things, clinical (e.g. therapeutic and preventative medicine (e.g., vaccination)) and research applications.

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.

A fusion protein, and compositions, kits, granulated antigens, vaccines and pharmaceutical compositions comprising the same. The invention also relates to a fusion protein and a composition comprising the fusion protein, a kit and application of the granulated antigen in preparation of a pharmaceutical composition or a vaccine. The granulated antigens are particularly suitable for vaccine production and vaccination and have advantages in the prevention and / or treatment of viral infections.

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 invention belongs to the technical field of biological medicines, and particularly relates to an mRNA vaccine for preventing or treating hepatitis B virus infection and application of the mRNA vaccine. The mRNA vaccine comprises mRNA for coding hepatitis B virus surface antigen or / and hepatitis B virus core associated antigen or / and hepatitis B virus front surface antigen 1 fusion IgG Fc segment protein, and the mRNA is wrapped by lipid nanoparticles to form a delivery system to be prepared into the mRNA vaccine. The vaccine preparation can specifically enhance humoral immune response and cellular immune response aiming at hepatitis B virus surface antigen or / and hepatitis B virus core related antigen or / and hepatitis B virus front surface antigen, and can be used for preventing and treating hepatitis B. All the components in the vaccine preparation can be widely obtained, the vaccine cost is effectively reduced, the vaccine yield is increased, and therefore the vaccine preparation has good practical application value.

Antibodies and antigen binding fragments that specifically bind to P. falciparum circumsporozoite protein are disclosed. Nucleic acids encoding these antibodies, vectors and host cells are also provided. The disclosed antibodies, antigen binding fragments, nucleic acids and vectors can be used, for example, to inhibit a P. falciparum infection.

The present application provides a bispecific antibody comprising a first antigen binding fragment binding to an HLA-A02 / HBsAg complex and a second antigen binding fragment binding to an activated T cell antigen, a single domain antibody binding to an HLA-A02 / HBsAg complex, a pharmaceutical composition comprising the bispecific antibody or the single domain antibody, and uses thereof.

The present invention pertains to the field of pharmaceutical technology. Specifically, the present invention relates to a zinc risedronate micro / nano adjuvant with sustained-release function formed by mineralization of zinc ions and risedronic acid as main components and its use as a vaccine adjuvant. The present invention also relates to a method for preparing zinc risedronate micro / nano adjuvant. The present invention also relates to a chemical composition, vaccine adjuvant and vaccine composition comprising zinc risedronate micro / nano adjuvant. The present invention also relates to a use of zinc risedronate micro / nano adjuvant as a vaccine adjuvant.

The invention provides a polypeptide for activating cellular immunity in chronic hepatitis B and application of the polypeptide, and belongs to the technical field of biological medicine. A polypeptide library is designed and synthesized on the basis of a preS1 structural domain for coding HBV large HBsAg, a full-length core protein Core, a polymerase protein fragment rich in T cell epitopes and an mRNA-PreS1CPX holoantigen sequence (as shown in SEQ ID NO.1) of full-length X protein HBX, and peptide fragments capable of activating T cell immunity are screened by utilizing ELISPOT and flow cytometry. Experimental results show that the polypeptide sequences as shown in SEQ ID NO.2-15 can promote HBV antigen specific immune response by stimulating CD8 + T lymphocytes to secrete IFN-gamma, so that immune activation treatment of hepatitis B is realized.

This disclosure provides an adenoviral vector comprising at least one modified capsid protein comprising the insertion or fusion of a first peptide partner, wherein the first peptide partner is covalently bonded to a second peptide partner that is joined to a decorating antigen by insertion or fusion; and wherein the decorating antigen comprises hepatitis B virus PreS1 and / or hepatitis B virus PreS2, or an immunogenic fragment thereof. The disclosure also provides a method of producing the adenoviral vector, and uses of the adenoviral vector in vaccines and pharmaceutical compositions.

The present invention encompasses engineered meganucleases which recognize and cleave a recognition sequence within an open reading frame (ORF) of the genome of at least two genotypes of the Hepatitis B virus (HBV). The present invention also encompasses methods of using such engineered meganucleases in a pharmaceutical composition and in methods for treating or reducing the symptoms of a HBV infection, or treating hepatocellular carcinoma (HCC). Further, the invention encompasses pharmaceutical compositions comprising engineered meganuclease proteins, nucleic acids encoding engineered meganucleases, and the use of such compositions for treating HBV infections or HCC.

The invention provides a nucleic acid molecule. The nucleic acid molecule comprises a nucleic acid sequence as shown in SEQ ID NO.2. The invention also provides a polypeptide which is encoded by the nucleic acid molecule. The invention further provides a recombinant plasmid, and the recombinant plasmid comprises the nucleic acid molecule. The invention also provides a preparation method of the recombinant protein. The preparation method comprises the following steps: optimizing an HBc gene into a nucleotide sequence comprising SEQ ID NO.2; constructing a recombinant plasmid based on the nucleic acid sequence; the recombinant plasmid is transfected into an HEK293 cell for expression; the cell supernatant is collected for purification of the recombinant protein. The HBc gene is optimized according to the codon preference of the HEK293 cell, and the codon adaptation index (CAI) value of the HBc gene is increased to 0.930. The expression system established by the invention has the remarkable characteristics of high efficiency and low pollution, not only overcomes the defects of the traditional expression system, but also provides a brand new strategy and technical support for efficient production of vaccines and development of nano-carriers.

The invention discloses a GNRH-I-MS2 fusion protein, a castrated MS2 virus-like particle subunit vaccine and a preparation method of the castrated MS2 virus-like particle subunit vaccine.

The invention relates to a GnRH-I-M1 recombinant protein. A vaccine prepared from the GnRH-I-M1 recombinant protein is high in antigen purity and good in safety, and has a good castration effect.

Disclosed herein is a method for enhancing immune response of a vaccine. The method includes preparing a Phycocyanin compound. The Phycocyanin compound includes at least one of C-phycocyanin (C-PC), Phycoerythrin (PE), Allophycocyanin (APC), phycocyanobilin (PCB), and combinations thereof. The method further includes administering the prepared Phycocyanin along with a vaccine composition to a living body.

Provided herein are methods for administering a hepatitis B virus surface antigen (HBsAg) to subjects with chronic hepatitis B to distinguish between responder subjects who respond to the HBsAg administration with an increase in an HBV antibody levels and non-responder subjects, and treating chronic hepatitis B in the responder subjects with an HBV therapy. Methods of excluding non-responder subjects from a clinical study are also provided.

The present invention relates to vaccine compositions, most notably vaccine compositions wherein the antigenic component is large, for example over 50 kDa, or multimeric, i.e. comprised of subunits. Such antigenic components are of particular interest, because they may represent antigenic components from pathogens that currently it is not possible to vaccinate against. The invention relates to a composition comprising a particle displaying an antigenic component, wherein said composition comprises an antigenic component comprising a first peptide tag, and a moiety comprising a second peptide tag, wherein the antigenic component and the moiety are linked via an isopeptide bond between said first and second peptide tags, and wherein the antigenic component is over 50 kDa, or alternatively is multimeric.

The invention discloses a polyantigen and a preparation method thereof. Wherein the polyantigen is formed by self-assembly of fusion protein, and the fusion protein comprises capsid protein and C-reactive protein. The multi-antigen is of a virus-like particle structure, wherein the C-reactive protein is located on the outer side of the virus-like particle structure. The polymer antigen is an icosahedron polymer particle, partially simulates spatial sites of a natural antigen pentamer, and improves the recognition efficiency of the generated antibody on the natural antigen.

Provided is a liquid formulation of a six combined vaccine containing DPT-IPV-Hib-HBs, in which a HBs antigen is stably adsorbed and retained to an aluminum adjuvant, and PRP as a Hib antigen is stably coupled and retained to a carrier protein. A method for producing a stable liquid formulation of a six combined vaccine against diphtheria, pertussis, tetanus, polio, Haemophilus influenzae type b (Hib), and hepatitis B (HepB), the method comprising the following steps of: (1) mixing diphtheria toxoid (D) and tetanus toxoid (T) with an aluminum adjuvant to produce a DT adjuvant; (2) mixing a hepatitis B surface (HBs) antigen with the DT adjuvant obtained in step (1) to produce a DT-HBs adjuvant; (3) mixing a pertussis antigen (P) with the DT-HBs adjuvant obtained in step (2) to produce a DPT-HBs adjuvant; (4) mixing inactivated poliovirus (IPV) with the DPT-HBs adjuvant obtained in step (3) to produce a DPT-IPV-HBs adjuvant; (5) adding a succinate phosphate buffer to the DPT-IPV-HBs adjuvant obtained in step (4), and then adding PRP (PRP-T conjugate) as a Hib antigen to produce a mixture of DPT-IPV-Hib-HBs adjuvant and PRP-T conjugate; and (6) adjusting pH of the mixture of DPT-IPV-Hib-HBs adjuvant and PRP-T conjugate obtained in step (5) to 5.4 to 5.9.

The present application relates to triterpene glycoside saponin-derived adjuvants, syntheses thereof, and intermediates thereto. The application also provides pharmaceutical compositions comprising compounds of the present invention and methods of using said compounds or compositions in the treatment of and immunization for infectious diseases.