66 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 provides a novel three-antigen HSV-2 adjuvant subunit vaccine as well as a preparation method and application thereof. The vaccine comprises herpes simplex virus recombinant protein and a composite adjuvant, the herpes simplex virus recombinant protein comprises extracellular domains of three proteins, namely HSV-2gE, gD and gC, wherein the amino acid sequences of the extracellular domains of the HSV-2gE, the gD and the gC are respectively shown as SEQ ID NO.1, SEQ ID NO.2 and SEQ ID NO.3; and the composite adjuvant is composed of CpG oligodeoxynucleotide and QS-21. Experiments prove that by adding the composite adjuvant composed of CpG oligodeoxynucleotide and QS-21, the immunogenicity, in-vivo protectiveness, virus removal and other immune functions of the HSV-2 subunit vaccine can be remarkably improved; meanwhile, the vaccine is a cross immune protection vaccine of an HSV-2 virus strain and an HSV-1 virus strain.

The invention provides a culture medium and a culture method for culturing human primary B lymphoma cells. The culture medium for culturing the human primary B lymphoma cells, disclosed by the invention, is prepared from an anti-immune globulin M antibody, a recombinant human CD40 ligand, CpG oligodeoxynucleotide 2006, superoxide dismutase, interleukin-2, interleukin-21 and interleukin-4. By using the culture medium and the culture method disclosed by the invention, effective and rapid amplification of the B lymphoma cells can be realized, the B lymphoma cells obtained by amplification maintain pathological characteristics of patients, the culture success rate and the amplification rate of the B lymphoma cells are improved, and a research basis can be provided for personalized treatment of the patients. The invention also provides B lymphoma cells obtained by in-vitro culture of the culture medium, and a method and application of the B lymphoma cells in curative effect evaluation and screening of drugs.

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.

Provided herein are immunogenic compositions comprising a mosaic influenza B virus hemagglutinin (HA) and a CpG oligonucleotide adjuvant. Also provided herein are immunogenic compositions comprising an inactivated influenza B virus described herein or inactivated split influenza B virus described herein and a CpG oligonucleotide adjuvant described herein, wherein the inactivated influenza B virus or inactivated split influenza B virus comprises a mosaic HA described herein. The immunogenic compositions may be used in a sequential immunization regimen. Also provided herein are methods of immunizing a subject against influenza virus disease (e.g., influenza virus disease caused by influenza B virus) using an immunogenic composition described herein. Further, provided herein are methods of preventing influenza virus disease (e.g., influenza virus disease caused by influenza B virus) in a subject using an immunogenic composition described herein.

Comprising a multivalent fusion protein and an exosome delivery carrier, and the content of the multivalent fusion protein is 70-90 [mu] g; wherein the multivalent fusion protein is a fusion protein formed by connecting a gB glycoprotein, a gC glycoprotein, a gD glycoprotein and a high-immunogenicity part of an important antigen segment selected from gE and gI; the exosome delivery carrier is a small vesicle extracted and purified from mesenchymal stem cells or HEK 293-F cells, the surface of the exosome delivery carrier is modified with a CD40L single-chain antibody, and the exosome delivery carrier is used for loading multivalent fusion protein; the porcine pseudorabies virus vaccine further comprises adjuvants, and the adjuvants comprise a TLR agonist, CpG oligonucleotide, synthetic liposome and a traditional aluminum salt adjuvant. The porcine pseudorabies virus vaccine also comprises a mucous membrane adsorbent, a penetration enhancer, a stabilizer and a preservative. The invention aims to construct a multivalent fusion protein complex containing a plurality of important antigen segments by using an advanced bioengineering technology, and provides a wider protection effect by combining an efficient exosome delivery platform and a method for enhancing immune response.

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.

Compounds and pharmaceutical compositions useful to treat cancer (e.g., lymphoma), neurodegenerative diseases, and autoimmune disorders include (1) a first nucleic acid sequence capable of binding to a transcription factor, for example, a signal transducer and activator of transcription (STAT) factor, such as STAT3, (2) a second nucleic acid sequence capable of binding a Toll-like receptor protein, for example, a CpG oligodeoxynucleotide, and (3) a ubiquitin ligase binding compound capable of binding a ubiquitin ligase protein, for example, a compound that is capable of binding a cereblon protein, such as lenalidomide, pomalidomide, or thalidomide.

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 present disclosure is directed to spherical nucleic acids (SNAs) comprising a nanoparticle core and an oligonucleotide shell attached to the external surface of the nanoparticle core, wherein the oligonucleotide shell comprises a mixture of class A CpG oligonucleotides and class B CpG oligonucleotides. The disclosure also provides methods of using the SNAs for, e.g., regulation of an immune response and gene regulation.

The present disclosure provides a method for treating cancer, which includes, inter alia, a) an intratumoral cell lysis step mediated by cryolysis, and b) an intratumoral administration step of a combination of immunotherapeutic agents including: 1) i) a TLR9 agonist CpG oligodeoxynucleotide, ii) an agonistic anti-CD40 monoclonal antibody, iii) an agonistic anti-OX40 monoclonal antibody, and iv) an anti-CTLA4 monoclonal antibody, or 2) i) a TLR9 agonist CpG oligodeoxynucleotide, ii) an agonistic anti-CD40 monoclonal antibody, iii) an anti-PD1 monoclonal antibody, and iv) an anti-CTLA4 monoclonal antibody.

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 the induction of novel Th1 response, the induction of cytotoxic T cells and anti-cancer / anti-allergic activity techniques. Provided is a combination of a CpG oligonucleotide and an STING agonist. Also provided is a composition which contains an STING agonist, can be used as a type-I adjuvant, and is characterized in that the STING agonist is administered together with a CpG oligonucleotide. Further provided is an anti-cancer agent comprising a CpG oligonucleotide and is characterized in that the CpG oligonucleotide is administered together with an STING agonist. Still further provided is a composition which contains a CpG oligonucleotide and can be used for reducing or eliminating the IgE-inducing activity of an STING agonist.

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.

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.

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.