119 results about "T cell response" patented technology

T cell responses are exquisitely antigen-specific and directed against peptide epitopes displayed by human leukocyte antigen (HLA) on the surface of presenting cells. In particular, class II HLA (HLA-II) is remarkably polymorphic, which allows for presentation of diverse peptide antigens to T cells, but also forms the basis for genetic associations with diverse immunopathologies across the spectrum of infectious disease and autoimmunity. Here, Applicants employ monoallelic immunopeptidomics to retrieve over 200,000 unique peptides presented by 41 HLA-II heterodimers covering major alleles across diverse ancestries. Applicants leveraged this expansive dataset to develop computational models that predict peptide antigens based on HLA-II binding properties and infer informative features of the protein antigens from which these peptides derive. Combining both peptide and (contextual) protein features, Applicants develop Context Aware Predictor of T cell Antigens (CAPTAn) to discover novel T cell epitopes from prokaryotes in the human microbiome and the viral pandemic pathogen SARS-COV-2.

The invention discloses neutral homogeneous lycium barbarum polysaccharide as well as a preparation method and application thereof. Through systematic structure characterization, it is clarified for the first time that the polysaccharide NLBPE1 is atypical arabinogalactan with 1, 5-alpha-L-arabinose as a bridging unit, and the polysaccharide NLBPE1 has a uniform molecular weight and a definite branched chain topological structure. The NLBPE1 serving as an adjuvant and an antigen are jointly entrapped in various delivery systems (such as PLGA nanoparticles, lipidosome, hydrogel and the like) to form the vaccine composition, so that the immunogenicity of the vaccine can be remarkably improved, and the antigen-specific T cell response can be enhanced. The invention provides an application scheme of the polysaccharide as a vaccine adjuvant in tumor immunotherapy and tumor prevention, and particularly shows a remarkable synergistic anticancer effect when the polysaccharide is combined with an immune checkpoint inhibitor for use. The polysaccharide has a clear structure, good biocompatibility and remarkable immunological enhancement activity, and has a wide application prospect of tumor vaccine adjuvants.

The invention belongs to the technical field of biological pharmacy, and relates to a bifunctional fusion protein targeting PD-1 / PD-L1 and IL-33 as well as a construction method and application of the bifunctional fusion protein. The bifunctional fusion protein comprises a PD-1 / PD-L1 antibody and a targeted IL-33 functional fragment, T cells are activated by blocking a PD-1 / PD-L1 signal to kill tumor cells, meanwhile, the level of IL-33 in tumor tissue is reduced, and the activity of IL-33 is inhibited. Researches show that the bifunctional fusion protein can increase infiltration of functional T cells, enhance T cell response and remodel a tumor microenvironment so as to generate an anti-tumor effect superior to that of combined treatment, and has a very good application prospect.

The present disclosure relates to the field of RNAs for the prevention or treatment of various infectious agents. In particular, the present disclosure relates to methods and agents for vaccination against coronavirus infection, influenza infection and / or RSV infection and induction of effective coronavirus, influenza virus and / or RSV antigen-specific immune responses, such as antibodies and / or T cell responses. Specifically, in one embodiment, the disclosure relates to a method comprising administering to a subject (i) a bivalent RNA vaccine encoding a peptide or protein comprising an epitope of SARS-CoV-2 spike protein (S protein), and (ii) a tetravalent RNA vaccine encoding a peptide or protein comprising an epitope of hemagglutinin (HA), the present invention relates to a method for inducing an immune response in a subject against a coronavirus S protein, in particular an S protein of SARS-CoV-2, and an influenza protein, in particular an HA protein of influenza A and B viruses.

Provided are a combination comprising a drug for treating hepatitis B and an antiviral agent, and a use thereof. The drug for treating hepatitis B comprises a nucleic acid or nucleic acid combination (e.g., an mRNA combination) encoding an antigen of hepatitis B virus. The combined use of the drug for treating hepatitis B and the antiviral agent can significantly reduce the number of liver HBV Core positive cells in an infected subject, greatly improve the HBV-specific T cell response level in the subject, and shows no obvious rebound of HBsAg after drug withdrawal.

To provide a method for inducing an immune response against a tumor-associated antigen in a subject.SOLUTION: A method comprises administering to a subject a CMV vector encoding a tumor-associated antigen in an amount effective to induce a CD8+ T cell response against the tumor-associated antigen, where the CMV vector does not express an active UL128 protein, an active UL130 protein, an active UL146 protein, or an active UL147 protein or respective orthologs thereof, and where the tumor-associated antigen comprises a specific amino acid sequence of 15 amino acid residues (MHC-E or MHC-II supertope peptide).SELECTED DRAWING: None

The present disclosure provides methods and kits for determining antigen-specific T cell responses in a subject based on the use of a whole blood sample rather than isolated, enriched, and / or extracted peripheral blood mononuclear cells. The use of a whole blood sample to measure antigen-specific T cell responses in a subject streamlines the method by reducing sample preparation and consumption. These methods for determining antigen-specific T cell responses in a subject include contacting a whole blood sample from the subject with at least one antigen to form a mixture, contacting the whole blood sample with at least one staining reagent, and analyzing the mixture for antigen-specific T cells.

The invention provides a novel vaccine adjuvant and application of the novel vaccine adjuvant in preparation of the vaccine adjuvant. The BCG-PSN and vaccine induced RBD specific IgG antibody and neutralizing antibody level are equivalent to those of an aluminum adjuvant, the BCG-PSN and vaccine induce Th1 biased T cell reaction, the induced T cell response level is obviously higher than that of the aluminum adjuvant, and K18-hACE2 mice are protected from being affected by Delta variant induced lung lesions. As a vaccine adjuvant, BCG-PSN has wide compatibility and safety, and has no toxic or side effect.

Provided is a method of using circular RNA as vaccine to treat cancer and design strategy to elicit specific and robust T cell response by promoting antigen presentation.

The invention relates to a self-adjuvant based on a virus source glycopeptide and an application of the self-adjuvant in preparation of a vaccine, the self-adjuvant is a glycopeptide fragment based on a varicella-zoster virus (VZV) source, and the self-adjuvant is a B cell epitope structural domain V50 glycopeptide (from 50 valine to 135 isoleucine, V50-I135) in glycoprotein E. The invention further relates to a preparation method of the self-adjuvant based on the virus source glycopeptide and application of the self-adjuvant based on the virus source glycopeptide in preparation of the vaccine. The V50 glycopeptide and the novel coronavirus RBD are subjected to fusion expression and then are coupled to the surfaces of the nanoparticles based on ferritin to form the self-adjuvant vaccine, so that the levels of RBD specific antibodies and pseudovirus neutralizing antibodies induced by the RBD nanoparticle vaccine can be remarkably enhanced, and the V50 glycopeptide has a synergistic effect in B cell response and T cell response of systemic systemic immunity and mucosal immunity at the same time. The immune protection effect of the novel coronavirus RBD nanoparticle vaccine is obviously improved.

Provided herein are multiepitope peptides comprising at least one mucin 1 (MUC1) peptide, having MHC affinity for at least one HLA serotype, and recognized by CD4+ T cell receptors and / or CD8+ T cell receptors. Also provided herein are compositions comprising the multiepitope peptides and a cationic lipid, including vaccine compositions. In various embodiments, the cationic lipid is R-DOTAP. The present invention also provides methods of using the multiepitope peptides, as well as compositions and vaccine compositions. These methods of use include methods for treating cancer in a subject and methods for inducing MUC-specific polyfunctional and cytolytic T cell responses in a subject.

A trivalent vaccine induces robust antibody and mucosal and systemic IFN-γ and Th17 T cell responses against Coccidioides and affords complete protection from fungal dissemination and disease. The combination of the three antigens of this trivalent vaccine can exert synergistic protection against lethality, disease and fungal dissemination. These robust responses can be further enhanced by use of one or more additional antigens described herein.

Compositions and methods of glycosylated virus-like particles (VLPs) displaying user-defined antigens and optionally encapsidating TLR ligands for targeting dendritic cell lectins have been developed. The VLPs employ ligands for a DC lectin e.g., DC-SIGN to activate dendritic cells (DC) and drive proliferation of antigen-specific CD8 and CD4-T cells specific for a user-defined antigen, such as a tumor antigens. In some forms, the compositions include aryl-mannose ligands to effectively generate DC-mediated TH-1 T cell responses to the user-defined antigen.

Described herein is an engineered viral subunit vaccine encoding ASFV capsid proteins (e.g., P72 and Penton) for use in pigs. The vaccine with either P72 or Penton tested in mice elicited significantly higher levels of antigen-specific IgM and IgG, increased frequency of antibody-secreting cells in the bone marrow, and higher quality germinal centers in the spleens of immunized mice. Enhanced T cell responses were also observed, with higher levels of IFN-γ and TNF-α in splenocytes. Immunogenicity assessments in pigs further supported these findings, with both MB-P72 and MB-PN180Q inducing robust B cell and T cell responses. These findings show that expression of capsid proteins P72 and Penton in membrane-bound forms via mRNA preserves their native multimeric structure and enhances their immunogenicity and provides a basis for an effective ASFV vaccine.

The present invention discloses a performance test system, device and method for a pancreatic cancer vaccine, which relates to the technical field of biomedical detection. This system includes units such as anti-adsorption storage, light-shielded transmission, buffer stabilization and interference correction detection. The device includes an intelligent syringe, a light-shielded dark box device and a microfluidic detection chip. The method covers steps such as standardized reconstitution, full-process light-shielded storage, specific detection and expiration date determination. By means of technical measures such as coating a specific coating on the inner wall of the syringe, designing a unique light-shielded structure, optimizing the buffer and detection system, etc., the LNP adsorption rate is significantly reduced, light damage is reduced, the buffer is stabilized, and the T cell response detection value is corrected. The present invention effectively improves the accuracy and reliability of the performance test of the pancreatic cancer vaccine, provides strong support for vaccine quality control and clinical application, and has innovation, practicability and good application prospects.

This disclosure provides a method for treating cancer in human subjects, comprising the administration of a recombinant polypeptide containing a cancer-specific CD8+ T cell epitope. The peptide, recognized by a major histocompatibility complex (MHC) molecule, can activate a T cell immune response to target cancer cells in the subject. This disclosure further provides a cancer-specific CD8+ T cell epitope constrained to an MHC molecule expressed by a specific HLA allele in the subject. This disclosure further provides a composition encoding a recombinant polypeptide capable of inducing an augmented memory CD8+ T cell response.

To provide HBV vaccines and methods for treating HBV.SOLUTION: Polypeptides are provided which are useful to elicit a protective immune response against one or more hepatitis B virus (HBV) antigens in a human. The immunogenic polypeptides described in this specification can elicit preventative and / or therapeutic immune responses in a human against one or more hepatitis B virus (HBV) antigens. Generally, the immunogenic polypeptides described in this specification contain highly conserved portions of HBV proteins in order to induce responses against epitopes that are identical in the vaccine antigen and in the infecting HBV present in the patient, while also excluding poorly conserved regions, thereby avoiding eliciting immunodominant T cell responses targeting epitopes that are not present in the infecting HBV strain of the patient.SELECTED DRAWING: Figure 1

The present invention relates to improved treatment of cancer with a PD-1 / PD-L1 antibody. In particular, the present invention is based on the discovery that patients having a TGF [beta]-specific T cell response are more likely to exhibit positive results in cancer treatment with a PD-1 / PD-L1 antibody. Thus, the present invention provides for the treatment of the group of patients with a PD-1 / PD-L1 antibody and proactively promoting a TGF [beta]-specific T cell response to improve treatment with a PD-1 / PD-L1 antibody.

The invention belongs to the technical field of biology, and particularly relates to a linear tandem antigen epitope polypeptide of African swine fever virus RAN polymerase and application of the linear tandem antigen epitope polypeptide. The amino acid sequence of the linear tandem antigen epitope polypeptide is shown as SEQ ID NO.4 or SEQ ID NO.5; the linear tandem antigen epitope polypeptide is obtained by linearly connecting an epitope polypeptide NP1249L-1, an epitope polypeptide H359L-1 and an epitope polypeptide H359L-2 in series, the epitope polypeptide NP1249L-1, the epitope polypeptide H359L-1 and the epitope polypeptide H359L-2 are obtained through screening, and the linear tandem antigen epitope polypeptide has the functions of inducing ASFV specific T cells and assisting in controlling ASFV infection and removing viruses, and experimental results show that the linear tandem antigen epitope polypeptide has the advantages that the linear tandem antigen epitope polypeptide is a novel linear tandem antigen epitope polypeptide; the epitope polypeptide has the capability of inducing ASFV specific T cell response, and a theoretical basis is provided for subsequent development of polypeptide vaccines and diagnostic preparations based on ASFV protein source epitopes.

The invention relates to the technical field of anti-tumor bionic nanomaterials, and discloses a preparation method and application of tumor-bacterial membrane chimeric nanoparticles, and the preparation method comprises the following steps: carrying out rotary evaporation on dimyristoyl phosphatidylcholine and cholesterol oleate to obtain an HDL rotary evaporation film; mixing the tumor cell membrane with the bacterial membrane to obtain a tumor-bacterial mixed membrane; pre-mixing apolipoprotein ApoA-1 with the tumor-bacteria mixed membrane, and adding the mixed solution into a container containing an HDL rotary evaporation membrane for hydration and reconstruction to obtain a crude suspension; and carrying out ultrafiltration purification on the crude suspension to obtain the tumor-bacterial membrane chimeric nanoparticles. The tumor cell membrane and the bacterial membrane are co-loaded on the high-density lipoprotein, so that the two membrane components can be co-delivered to the dendritic cells to induce maturation of the dendritic cells, are accumulated in tumors and drainage lymph nodes in vivo, activate CD8 + T cell response and have an inhibition effect on tumor growth.

The present invention relates to the identification and use of tumor epitopes from subjects with brain cancer, and particularly to epitopes from brevican, neurocan, versican, and aggrecan and their use in formulating cancer vaccines for treatment of tumor patients. In some preferred embodiments the methods provide a means of identifying T cell epitopes in proteins upregulated in brain tumors and the selection of those peptides which can stimulate T cell responses in individual subjects with a particular combination of HLA alleles. It further identifies the T cell exposed motifs comprised in T cell epitopes and enables the design of peptides with alternative amino acids in positions other than the T cell exposed motifs. In preferred embodiments, the MHC I and MHC II alleles of the affected subject are determined, and peptides are selected which bind to their MHC molecules with a desired affinity to elicit stimulation.

The invention is applicable to the field of gene engineering, and provides a mycobacterium tuberculosis ESAT-6-LS protein nanoparticle, a preparation method and application thereof, the mycobacterium tuberculosis ESAT-6-LS protein nanoparticle is formed by sequence fusion of mycobacterium tuberculosis ESAT-6 protein and LS protein, and the amino acid sequence of the mycobacterium tuberculosis ESAT-6-LS protein nanoparticle is shown as SEQ ID NO: 2 in a sequence table. The ESAT-6-LS protein nanoparticle provided by the invention is non-toxic and free of pathogenicity, can ensure that a vaccine has good biological safety, and is suitable for clinical application. Animal experiments show that after a mouse is immunized by the ESAT-6-LS protein nanoparticle, strong humoral immunity (antibody generation) and cellular immunity (T cell response) can be stimulated at the same time, and it is proved that the recombinant ESAT-6-LS protein nanoparticle vaccine can effectively induce specific immune protection.

The invention relates to the technical field of medicines, in particular to a zinc ion polypeptide compound immunologic adjuvant as well as a preparation method and application thereof. The preparation method comprises the following steps: mixing polypeptide, a PBS buffer solution, new coronavirus S protein, a CpG ODN immune activator and zinc ions, and standing to obtain the zinc ion polypeptide compound immunologic adjuvant. A dual-adjuvant system mixed with CpG ODN shows excellent performance in activation of lung tissue immunity, and in the cellular immunity level, the response intensity of CD4 + T and CD8 + T cells is enhanced, and formation of related tissue resident memory T cell phenotypes is promoted; on the humoral immunity level, a Gel (Zn < 2 + >) and CpG ODN dual-adjuvant system obviously stimulates the increase of the number of B cells and the activation, and can effectively stimulate the secretion of a main antibody sIgA for mucosal immunity. On the whole, the dual adjuvants realize the synergistic enhancement of T cell (containing TRM) and B cell immunity.

The invention belongs to the technical field of biology, and particularly relates to a T cell epitope polypeptide based on ASFV F1055L or P1192R protein, the T cell epitope polypeptide comprises a polypeptide F1055L-1, a polypeptide F1055L-2, a polypeptide F1055L-3 and a polypeptide P1192R-1, and the amino acid sequence is shown as SEQ ID NO.1-4. The polypeptide is obtained through screening and has the characteristics of inducing ASFV specific T cells and assisting in controlling ASFV infection and virus clearance. In-vitro experiments prove that the epitope polypeptide has the capability of inducing ASFV specific T cell response, and a theoretical basis is provided for subsequent development of polypeptide vaccines and diagnostic preparations based on ASFV protein source epitopes.

This invention relates to the application of methyltransferase inhibitors as adjuvants for respiratory syncytial virus (RSV) vaccines and allergy vaccines. Methyltransferase inhibitors, as adjuvants for RSV vaccines or allergy vaccines, can target and regulate the antigen presentation function of vaccine-induced memory dendritic cells (DCs), thereby regulating the balance of T cell responses and balancing the dominant Th2 and / or Th17 cellular immune responses induced by RSV vaccines or allergy vaccines. This allows the vaccine recipient to develop a balanced immune memory, providing protection while preventing the occurrence of vaccine-enhanced inflammatory diseases when RSV infection or allergen stimulation occurs, thus being both safe and effective.

According to the invention, a novel immune checkpoint molecule SIDT1 is found. The SIDT1 is a powerful T cell inhibition factor mainly expressed on CD8 < + > T cells. A series of SIDT1 inhibitors are identified in the invention. The SIDT1 inhibitor can enhance the anti-tumor CD8T cell reaction and limit tumor progression, so that a new thought is provided for treatment and prevention of related tumor patients with PD-1 treatment resistance.

The invention provides a method for detecting subtype pSTAT4 and Ki67 signals of peripheral blood T lymphocytes of machin through flow cytometry, and belongs to the technical field of biological detection. According to the method, the integrated analysis of the multi-dimensional functional state of the cynomolgus monkey T lymphocyte is realized, key signal channel activation and proliferation information of different subgroup cells can be synchronously obtained through a single experiment, and the detection comprehensiveness and efficiency are greatly improved. According to the method, an accurate tool capable of directly evaluating the response intensity and proliferation potential of T cells is provided for immune mechanism research based on a machin model, particularly immune therapy or disease research related to regulation and control of pathways such as IL-12 / STAT4 and the like, and the data dimension and reliability of preclinical immunological evaluation are remarkably enhanced.

The present disclosure relates to a novel vaccine strategy against hepatitis B virus (HBV) infection, which is a major cause of chronic liver disease and hepatocellular carcinoma worldwide. The disclosure provides fusion proteins that target dendritic cells (DCs), the key antigen-presenting cells of the immune system, and deliver HBV-derived peptides to both the major histocompatibility complex (MHC) class I and II pathways, thereby inducing strong and specific humoral and cellular immune responses against the viral envelope and core antigens. The disclosure also provides methods of using the fusion proteins for the prevention or treatment of HBV infection and its complications. The inventors have demonstrated in a mouse model that the DC-targeting HBV vaccine candidates can elicit robust antibody and T cell responses, which are essential for the clearance of the virus and the protection from chronic infection.

The invention belongs to the technical field of preparation of vaccine immunologic adjuvants, and discloses a surface-modified aluminum hydroxide nanoparticle adjuvant as well as preparation and application thereof. The aluminum hydroxide-based adjuvant is a next-generation aluminum hydroxide-based adjuvant at an optimal level specially optimized for veterinary vaccines. The formula of the adjuvant solves the limitation of the traditional aluminum hydroxide adjuvant, including poor cellular immune induction and variable efficacy in large animals. The adjuvant promotes balanced Th1 / Th2 immune response, reduces local injection site reaction, and improves the shelf life of the vaccine. The preparation method comprises ultrasonic homogenization and co-precipitation under pH control, vaccine compositions containing the adjuvant, and uses of the adjuvant in prevention of infectious diseases in animal husbandry, companion animals and poultry. Experimental data show that in bovine respiratory disease and avian influenza models, compared with traditional adjuvants, the immunogenicity is excellent, the antibody titer is increased by 3 times, and CD8 + T cell response is enhanced.

The present disclosure relates to compositions and methods for enhancing T cell response and / or CAR cell expansion and / or maintenance in vivo and / or in vitro. For example, a method of enhancing T cell-based therapy comprises administering genetically modified T cells comprising a first chimeric antigen receptor (CAR) and a second CAR, wherein a binding domain of the first CAR binds a first antigen, and a binding domain of the second CAR binds a second antigen. The first antigen is different from the second antigen. In embodiments, the first CAR binds a surface molecule or antigen of a white blood cell.