44 results about "CPG-oligonucleotide" patented technology

The invention belongs to the technical field of biological medicine, and particularly discloses a composite vaccine adjuvant as well as a preparation method and application thereof. The composite vaccine adjuvant provided by the invention is an oil-in-water emulsion, and simultaneously contains squalene, polysorbate 80, sorbitan trioleate, polyinosinic acid (Poly I: C) and CpG oligodeoxynucleotide (CpG-ODN). The sequence-optimized CpG-ODN and Poly I: C are used in a specific emulsion system in a combined mode, a remarkable synergistic immune enhancement effect can be generated, the induced humoral immunity and cellular immunity response level is remarkably higher than the sum of the effects when all the components are independently used, and the composite adjuvant is good in stability, high in immunostimulatory activity and suitable for clinical application. The immune effect can be remarkably improved by combined application with various vaccine antigens. The invention also provides a preparation method and application of the composite vaccine adjuvant.

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 relates to a novel three-antigen HSV-2 subunit vaccine as well as a preparation method and application thereof, and belongs to the technical field of biology. The novel three-antigen HSV-2 subunit vaccine comprises antigens and a composite adjuvant, the antigens comprise HSV-2 gB2 envelope glycoprotein, HSV-2 gC2 envelope glycoprotein and HSV-2 gD2 envelope glycoprotein, and the composite adjuvant is CpG oligonucleotide and an aluminum adjuvant; the vaccine provided by the invention can induce a high-level neutralizing antibody, and widens targets for developing a novel multi-target antigen HSV-2 virus vaccine.

The invention relates to a novel HSV-2 three-antigen recombinant protein vaccine composition and application thereof, and belongs to the technical field of biology. The vaccine composition comprises an antigen and a composite adjuvant, the antigen is HSV-2 gC2-gD2-gE2 three-antigen tandem recombinant protein, and the composite adjuvant is CpG oligonucleotide and an aluminum adjuvant; the amino acid sequence of the HSV-2 gC2-gD2-gE2 three-antigen tandem recombinant protein is as shown in SEQ ID NO. 1, and the nucleotide sequence of the HSV-2 gC2-gD2-gE2 three-antigen tandem recombinant protein is as shown in SEQ ID NO. 2. The time cost and the economic cost in the protein preparation process are greatly reduced, and compared with an original trivalent combination vaccine, the trivalent combination vaccine can induce the level of specific antibodies generated by mice and the virus neutralizing capacity not to be reduced, so that a brand new thought is provided for developing advanced HSV-2 virus vaccines with multiple target antigens, and the trivalent combination vaccine is worthy of popularization and application. Meanwhile, the invention also provides a safe and effective HSV-2 virus candidate vaccine.

The present disclosure pertains to the recognition that immune responses mediated by CpG oligonucleotides can be affected by the stereochemistry of modified internucleotidic linkages such as phosphorothioates. In some embodiments, the present disclosure relates to chirally controlled CpG oligonucleotide compositions comprising CpG oligonucleotides comprising multiple modified internucleotidic linkages such as phosphorothioate linkages, wherein the oligonucleotides comprise one or more CpG region motifs having defined stereochemistry patterns of chiral internucleotidic linkages. In some embodiments, CpG oligonucleotides comprising one or more CpG region motifs are capable of agonizing an immune response. In some embodiments, CpG oligonucleotides comprising one or more CpG region motifs are antagonistic. Methods for making and using chirally controlled CpG oligonucleotide compositions are also described. In some embodiments, no immune modulation is desired, and the present disclosure provides methods of identifying chirally controlled oligonucleotide compositions which have decreased immune modulation.

The application discloses a deformable red blood cell preparation targeting liver and a preparation method and application thereof. The deformable red blood cell preparation comprises red blood cells and a deformable agent combined on the red blood cell membrane. The deformable agent comprises a CpG oligonucleotide. The deformable red blood cell preparation of the application highly targets liver by using the natural immune homing property of deformable red blood cells, and can reduce the toxic side effects of drugs and increase the safety of drug administration. Meanwhile, the deformable red blood cell preparation of the application has a simple preparation process, and raw materials are economical and easy to obtain, and the preparation process does not need to depend on complex equipment and is easy to industrialize.

The application discloses CpG-containing oligodeoxynucleotide (ODN) with the function of regulating the body's immune capacity and application thereof. The oligodeoxynucleotide in the application is different from the design concept of traditional A-type CpG ODN in sequence and structure, embodies the complex drug-making rule and overcomes the problem of traditional A-type CPG in drug-making. The oligodeoxynucleotide has excellent activity of regulating the body's immune function in vitro and in vivo, can stimulate the production of I, II and III type interferons, regulates the Th1 type immune response, and inhibits the Th2 type and Th17 type inflammatory response. Therefore, the oligodeoxynucleotide can prevent and treat allergic diseases caused by Th2 type immune response, including allergic rhinitis, atopic dermatitis, asthma, chronic obstructive pulmonary disease, eosinophil and Th17 related diseases, can prevent and treat the infection and spread of respiratory or non-respiratory pathogenic microorganisms including viruses, bacteria, fungi and parasites, can improve the immune level of the elderly and immunodeficient population, can convert "cold tumor" into "hot tumor", improve the effect of cancer immunotherapy, can prevent and treat central nervous system diseases related to immune dysfunction such as Alzheimer's disease, and can be applied to other diseases related to immune dysfunction.

The application relates to the technical field of biological medicine, and particularly discloses CpG oligodeoxynucleotides and application thereof. The CpG oligodeoxynucleotide has a sequence as shown in any one of SEQ ID NO. 3-6, 9, and preferably has a sequence as shown in SEQ ID NO. 3-6. The CpG oligodeoxynucleotide can effectively activate the immune system of a human body or an animal, has the functions of preventing and treating pathogenic microorganism infection in a broad spectrum, has the function of improving the immunogenicity of a common vaccine, and can be applied as a human or animal vaccine adjuvant.

The application of CpG oligonucleotides in drugs for diabetic cardiac autonomic neuropathy: Experiments have confirmed that CpG oligonucleotide 1826 can reduce the activation of satellite glial cells in the stellate ganglion and the expression of inflammatory cytokines, inhibit the expression of purine 2Y12 receptors, and reduce lipid peroxidation damage to alleviate ferroptosis in stellate ganglion neurons, thereby improving cardiac autonomic nerve function. Examples of CpG oligonucleotide 1826 demonstrate that CPG-ODN with anti-inflammatory effects or with anti-damage protective effects on the sympathetic nervous system has preventive and therapeutic effects in diabetic cardiac autonomic neuropathy and sympathetic nerve injury-related diseases.

A pharmaceutical composition comprising: i) a herpes gE protein, an active fragment of the protein, a variant of the protein, or a mixture of at least two of them; ii) an immunostimulatory composition comprising a saponin and a CpG oligodeoxynucleotide, or consisting of an adjuvant comprising a saponin and a CpG oligodeoxynucleotide. Use of the pharmaceutical composition in the preparation of a medicament for preventing and / or treating a varicella-zoster virus infection and / or a varicella-zoster virus mediated disease. The pharmaceutical composition achieves an unexpected technical effect and can mediate a stronger immune response.

In one aspect, provided herein are immunogenic compositions comprising CpG oligonucleotide adjuvant, and a recombinant neuraminidase, wherein the recombinant neuraminidase comprises a globular head domain of influenza virus neuraminidase and a tetramerization domain, and wherein the recombinant neuraminidase lacks influenza virus neuraminidase stalk, transmembrane and cytoplasmic domains. In another aspect, provided herein are methods of immunizing a subject against influenza virus using such immunogenic compositions. In another aspect, provided herein are methods of immunizing a subject against influenza virus using such immunogenic compositions.

The invention relates to lipid nanoparticles containing an adjuvant for mucosal administration and a preparation method of the lipid nanoparticles. The lipid nanoparticles comprise total lipid, an adjuvant and an active ingredient, wherein the total lipid is composed of cationic lipid C12-200, non-cationic phospholipid, cholesterol and a derivative thereof, and pegylated lipid; wherein the adjuvant is selected from at least one of AS03, MF59, monophosphoryl lipid A, miniaturized monophosphoryl lipid A, ophiopogonin D, saponin QS21, QS7, QS17, QS18, CpG oligonucleotide, 2 '3'-ring GMP-AMP, 3 '3'-ring GMP-AMP, alpha GC, Trehalose-6, 6-dibehenate, cholera toxin B subunit and flagellin.

The present invention relates to a combined treatment composition for tumor treatment and a combined treatment method. The combined treatment composition or a medicine kit comprises a therapeutically effective amount of a platinum chemotherapeutic drug, and a therapeutically effective amount of CpG oligonucleotide and a therapeutically effective amount of R848. The present invention further provides a combined treatment method for treating a tumor by means of the combined treatment composition or the medicine kit. Firstly, a low-dose chemotherapeutic drug is used to kill a tumor so as to release a tumor neoantigen, such that a body immune system autonomously identifies and screens the neoantigen, and then CpG oligonucleotide and an R848 activator of immune response are used to induce and promote the body to generate immune response specific to the tumor neoantigen, such that the anti-tumor function of T cells is improved and enhanced, thereby achieving the effect of inhibiting tumor growth.

The present invention discloses a multi-substrate adhesive hydrogel capable of efficiently delivering nucleic acid molecules and its application in tumor treatment. The preparation steps of the hydrogel are as follows: preparing a MXene nanosheet solution by hydrofluoric acid etching; preparing a disulfide solid powder by recrystallization; mixing the disulfide solid powder with the MXene nanosheet solution and stirring at room temperature to obtain solution A; mixing CpG oligonucleotide with solution A and dialyzing to obtain an ONMs nanoparticle solution; grafting sodium alginate and amino-modified ATP aptamer to obtain DNA SA solution; ONMs nanoparticle solution and DNA SA solution was mixed and incubated at room temperature to obtain DNA SA@ONMs solution; DNA The SA@ONMs solution was mixed with acrylamide, and then an ionic crosslinker, a crosslinker, a crosslinking accelerator, and an initiator were added in sequence. The mixture was stirred at room temperature and allowed to stand to solidify into a gel, thereby obtaining a multi-substrate adhesion hydrogel.

The application discloses a composite adjuvant containing CpG oligodeoxynucleotide and aluminum adjuvant, and a new coronavirus COVID-19 inactivated vaccine using the composite adjuvant. The CpG oligodeoxynucleotide is used in combination with the aluminum adjuvant, and a strong immune enhancement effect can be generated. When the composite adjuvant is applied to the new coronavirus COVID-19 inactivated vaccine, the residence time of the antigen in the body can be greatly prolonged, and the hydrolysis of the antigen by various hydrolytic enzymes is reduced. The preparation method of the new coronavirus COVID-19 inactivated vaccine provided by the application is simple, the quality is easy to control, the vaccine is easy to mass-produce, has good safety, low toxic and side effects, and is particularly suitable for being used for the prevention and treatment of the new coronavirus COVID-19 in various populations, including the low-immunity population such as the middle-aged and the old.

The present invention provides an adjuvant comprising a B-type CpG oligodeoxynucleotide (CpG ODN), a modification thereof, or a complex thereof, to be administered together with an mRNA vaccine in which mRNA is encapsulated in particles. The adjuvant contains the B-type CpG ODN that is present independently of the particles that encapsulate mRNA. This adjuvant can enhance antigen-specific cytotoxic T cell (CTL) induction by mRNA vaccines.

The invention relates to a CpGODN molecule and an application thereof. According to the CpG adjuvant, by optimizing a core CpG motif (such as 5 '-GACGTT-3') and a flanking sequence thereof, the activation efficiency of a Toll-like receptor 9 (TLR9) is remarkably improved. In order to further enhance the stability and the targeting property of the CpG adjuvant, the CpG oligonucleotide is subjected to phosphorothioate modification, and the CpG adjuvant shows excellent immune activation ability in both in-vitro and in-vivo experiments, can significantly enhance the immunogenicity of vaccines, overcomes the species effect, has a good stimulation effect on both mouse and human lymphocytes, and can be used for preparing the immunopotentiator. The compound has a remarkable synergistic effect with an aluminum adjuvant, realizes relatively balanced cell humoral immune response, and has a wide application prospect in the field of vaccine development.

Pharmaceutical compositions and compounds comprising a phosphorothioated CpG oligodeoxynucleotide linked to a DNA oligonucleotide that is hybridized an RNA aptamer are useful in methods of treating cancer (such as leukemia) and methods of inhibiting DNA methyltransferase. In embodiments, the RNA aptamer binds to an intracellular target such as DNMT1, NF-kB, RUNX1, MYC, MYB, ETS, PAX5, MDM2, F0XM1, PU.l, STAT3, STATS. STAT6, FAD, ATP5B, or beta-catenin.

Compositions and pharmaceutical compositions are provided herein which can comprise oligonucleotides, such as synthetic CpG oligonucleotides, related to immune responses, and / or other ingredient(s). Compositions and pharmaceutical compositions described herein include those that result in a TLR9 activation. Also described are methods, among other things, for accelerating wound healing, for cell expansion, and improved methods of activated cell expansion by compositions and pharmaceutical compositions herein.

In one aspect, the present disclosure relates to adjuvant nanoparticles comprising aluminum and / or CpG oligodeoxynucleotides. In particular embodiments, the nanoparticles have an average size of less than about 100 nm. Also provided herein are methods of making the nanoparticles using a microfluidic device.

The disclosure provides, inter alia, oligonucleotides comprising 6-thio-2′-deoxy-guanosine residues. The oligonucleotides comprising said residues are used in pharmaceutical compositions and methods for treating cancer. The invention also includes CpG oligodeoxynucleotides in combination with the 6-thio-2-deoxy-guanosine residues in said pharmaceutical compositions and methods for treating cancer. Oligonucleotides of the invention may also include additional therapeutic moieties or exonuclease resistant moieties. The compositions and methods of the invention may employ additional pharmaceutical entities for the treatment of cancer.

The application discloses a CpG oligodeoxynucleotide, which has a nucleotide sequence as shown in any one of SEQ ID NO. 1-8; or a nucleotide sequence with one or more nucleotides substituted or added to the nucleotide sequence as shown in SEQ ID NO. 8 and with the same function. The application has the beneficial effect that animal experiments prove that a vaccine containing the CpG oligodeoxynucleotide has a higher IgG binding antibody level in the serum GMT detection result of mice 14 days after the second immunization, is obviously better than the negative control and the positive control, and the effect is related to the specific base sequence of the CpG oligodeoxynucleotide. The above results prove that the CpG oligodeoxynucleotide can obviously enhance the immunogenicity of the vaccine, reduce the number of immunization needles, reduce the antigen usage, and has a better vaccine adjuvant effect when applied to the preparation of the vaccine.

The invention relates to oligonucleotides, compositions and methods thereof. The present disclosure relates to the recognition that immune responses mediated by CpG oligonucleotides may be stereochemically affected by modified inter-nucleotide linkages (e.g., phosphorothioates). In some embodiments, the present disclosure relates to chirally controlled CpG oligonucleotide compositions comprising a CpG oligonucleotide comprising a plurality of modified inter-nucleotide bonds, such as phosphorothioate bonds, such as phosphorothioate bonds, etc. Wherein the oligonucleotide comprises one or more CpG region motifs having a defined stereochemical pattern of chiral inter-nucleotide bonding. In some embodiments, a CpG oligonucleotide comprising one or more CpG region motifs is capable of agonizing an immune response. In some embodiments, CpG oligonucleotides comprising one or more CpG region motifs are antagonistic. The present invention also describes methods for making and using chirally controlled CpG oligonucleotide compositions. In some embodiments, immunomodulation is not required, and the present disclosure provides methods of identifying oligonucleotide compositions with reduced chiral control of immunomodulation.

The invention provides a DNA (Deoxyribose Nucleic Acid) nano tumor vaccine, which comprises a plurality of DNA nano flowers of a CpG oligonucleotide adjuvant which is copied repeatedly, the DNA nano flowers are loaded with a plurality of DNA-coupled KRAS G12D antigen peptides and a DNA-coupled lymph node targeting fragment DSPE-PEG2000, and the sequence of the KRAS G12D antigen peptides is shown as SEQ ID NO.5. The invention also provides a preparation method of the DNA nano tumor vaccine, and the preparation method of the DNA nano tumor vaccine is characterized in that the DNA nano flowers are loaded with a plurality of DNA-coupled KRAS G12D antigen peptides and a plurality of DNA-coupled lymph node targeting fragments DSPE-PEG2000. The invention also provides a preparation method of the DNA nano tumor vaccine. The invention also provides an application of the DNA nano tumor vaccine in preparation of drugs for immunotherapy of cancers. After subcutaneous injection, the nano vaccine can effectively deliver a CpG ODN adjuvant and G12D antigen peptide into lymph nodes in a targeted manner, induce a strong immune stimulation reaction and significantly inhibit the growth of pancreatic cancer, provides an effective strategy for pancreatic cancer immunotherapy, and has a clinical transformation prospect.

The invention provides a novel adjuvant subunit rabies virus vaccine as well as a preparation method and application thereof, the vaccine takes a rabies virus (RABV) glycoprotein extracellular domain prepared by a gene recombination technology as an antigen, and takes a combination of CpG oligodeoxynucleotide and QS21 as an adjuvant. A contrast experiment is carried out on the vaccine, an LNP-mRNA-G-H270P vaccine, a commercial inactivated vaccine and an aluminum adjuvant subunit vaccine, and the result shows that the vaccine can induce a remarkably higher RABV-G specific IgG antibody and virus neutralizing antibody titer, and the humoral immune response is superior to that of other vaccines; meanwhile, moderate and effective Th1 type cell immune response can be induced, so that protective immunity can be supported; 100% protection is achieved in a lethal RABV attack experiment, and the protection effect is equivalent to that of an mRNA vaccine and is remarkably superior to that of an aluminum adjuvant vaccine and a commercial inactivated vaccine. The vaccine provided by the invention has a controllable immune activation mechanism and relatively high safety, avoids the storage risk and excessive inflammatory response of a nucleic acid technology, and is a more reliable and universal choice in the current vaccine technology.

The present application relates to a kind of nucleotide, vaccine comprising it and composite vaccine adjuvant.The sequence of the nucleotide is shown as SEQ ID No:1.Relative to conventional technology, the beneficial effects of the present application include: the present application adopts new optimized sequence, provides a kind of nucleotide, the nucleotide can be as CpG oligonucleotide adjuvant, induces vaccine antigen to produce stronger humoral immunity, cellular immunity level and anti-tumor immune effect etc., has obvious clinical application value and vaccine development value.Moreover, using the immunoadjuvant of the present application helps to reduce the dose of clinical use vaccine, improves safety.

The application provides a manganese dioxide nanomaterial, which comprises manganese dioxide nanoparticles and a carrier substance combined on the surface of the manganese dioxide nanoparticles; the carrier substance comprises CpG oligonucleotide and / or antigen; the antigen comprises protein antigen and / or polypeptide antigen. The manganese dioxide nanomaterial provided by the application greatly improves the immune stimulation of the immune adjuvant CpG, is used for improving the immune protection function of a vaccine, and solves the inherent defects that the oligonucleotide CpG as an immune stimulant is difficult to enter the lymph nodes of the body, and a large amount of CpG is needed to effectively improve the immune response; and as a vaccine adjuvant, the manganese dioxide nanomaterial can carry antigen, especially protein antigen, effectively improves the uptake of immune cells in the lymph nodes to the antigen, and thus improves the immunogenicity of the antigen. Meanwhile, the nanomaterial is biodegradable, and in a weak acid environment such as a lysosome, the nanomaterial can be gradually degraded into manganese ions (Mn 2+ ), and finally discharged out of the body.

This invention provides multiple oligodeoxyribonucleotides (ODNs), including CpGs, that have the function of modulating the immune system of organisms, and their uses. These oligodeoxyribonucleotides differ in sequence and structure from the design concepts of conventional type A CpG ODNs, demonstrating complex drug discovery rules and solving the challenges of conventional type A CpG drug discovery. They exhibit excellent activity in modulating the immune function of organisms both in vitro and in vivo, stimulating the production of type I, II, and III interferons, enhancing the Th1 immune response, and suppressing Th2 and Th17 inflammatory responses. Therefore, they can prevent and treat allergic diseases caused by Th2 immune responses, such as allergic rhinitis, atopic dermatitis, asthma, chronic obstructive pulmonary disease, eosinophilic granulocyte and Th17-related diseases, prevent and treat infection and transmission of respiratory or non-respiratory pathogenic microorganisms such as viruses, bacteria, fungi, and parasites, and improve immune levels in elderly and immunocompromised populations. It can transform "cold tumors" into "hot tumors," improve the effectiveness of cancer immunotherapy, prevent and treat central nervous system diseases associated with immune dysregulation such as Alzheimer's disease, and can also be used for other diseases associated with immune dysregulation.

Provided is a stable vaccine comprising a protein antigen having a pI at or above about 7.0 or at least four consecutive positively charged amino acids, and a CpG oligonucleotide, and a buffer. Methods of stabilizing such subunit vaccines and assays determining whether the antigen adheres to container walls are also provided.

The invention discloses a preparation method of rimosella anatipestifer and escherichia coli bivalent multivalent inactivated vaccine, and relates to the field of preparation of canine anatipestifer vaccine.The preparation method comprises the steps that a CpG immune synergist and a nano slow-release carrier suspension are mixed to obtain a composite water-based adjuvant; adding the purified and inactivated antigen concentrated solution of rimorella anatipestifer and O78 type escherichia coli into a composite water-based adjuvant, and carrying out high-pressure homogenization to obtain a vaccine semi-finished product; standing and defoaming the vaccine semi-finished product to obtain the vaccine; the preparation method of the CpG immune synergist comprises the following steps: grafting CpG oligonucleotide onto sodium alginate; wherein the preparation of the nano sustained-release carrier suspension comprises the step of preparing nano sustained-release microspheres from polylactic acid and chitosan, and the animal injection site inoculated with the vaccine has no adverse reactions such as obvious swelling and induration, and is fast to absorb.