175 results about "T cell response" patented technology

The invention belongs to the field of biological medicine, and particularly relates to a mouse MC38 colorectal cancer neoantigen polypeptide and immunologic adjuvant composition and application of the mouse MC38 colorectal cancer neoantigen polypeptide and immunologic adjuvant composition in tumor treatment, and amino acid sequences of the neoantigen polypeptide are shown as SEQ ID No.2, 13, 16 and 17. Four tumor neoantigen polypeptides really having immunogenicity are obtained through screening, the obtained tumor neoantigens are compatible with PolyI: C to prepare the vaccine preparation, and after mice are treated by the MC38 tumor vaccine preparation, the growth of tumors can be effectively inhibited; and the survival time of the mouse is prolonged, and the new antigen vaccine preparation generates very effective T cell reaction in the tumor-bearing mouse body.

This disclosure relates to the field of RNA to prevent or treat coronavirus infection. In particular, the present disclosure relates to methods and agents for vaccination against coronavirus infection and inducing effective coronavirus antigen-specific immune responses such as antibody and / or T cell responses. Specifically, in one embodiment, the present disclosure relates to methods comprising administering to a subject RNA encoding a peptide or protein comprising an epitope of SARS-COV-2 spike protein (S protein) for inducing an immune response against coronavirus S protein, in particular S protein of SARS-COV-2, in the subject, i.e., vaccine RNA encoding vaccine antigen.

Transgenic rodents and rodent cells that express components of the human immune system, and their uses in generating human T cell receptors (TCRs). A genetically modified rodent comprising a TCR alpha gene locus comprising unrearranged human TCR alpha variable gene segments and a human TCR alpha constant region, and a TCR beta gene locus comprising unrearranged human TCR beta variable gene segments and a human TCR beta constant region. Use of hTCR transgenic rodents to generate antigen-specific CD8+ T cell responses for the discovery of fully human TCR sequences with therapeutic potential.

The present disclosure provides isolated monoclonal antibodies that specifically bind to LAG-3 with high affinity, particularly human monoclonal antibodies. Preferably, the antibodies bind human LAG-3. In certain embodiments, the antibodies bind both human and monkey LAG-3 but do not bind mouse LAG-3. The invention provides anti-LAG-3 antibodies that can inhibit the binding of LAG-3 to MHC Class II molecules and that can stimulate antigen-specific T cell responses. Nucleic acid molecules encoding the antibodies of the invention, expression vectors, host cells and methods for expressing the antibodies of the invention are also provided. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. This disclosure also provides methods for detecting LAG-3, as well as methods for treating stimulating immune responses using an anti-LAG-3 antibody of the invention. Combination therapy, in which an anti-LAG-3 antibody is co-administered with at least one additional immunostimulatory antibody, is also provided.

This disclosure relates to the field of RNA to prevent or treat coronavirus infection. In particular, the present disclosure relates to methods and agents for vaccination against coronavirus infection and inducing effective coronavirus antigen-specific immune responses such as antibody and / or T cell responses. Specifically, in one embodiment, the present disclosure relates to methods comprising administering to a subject RNA encoding a peptide or protein comprising an epitope of SARS-CoV-2 spike protein (S protein) for inducing an immune response against coronavirus S protein, in particular S protein of SARS-CoV-2, in the subject, i.e., vaccine RNA encoding vaccine antigen.

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 relates to the technical field of tumor vaccines, and provides a novel mRNA (messenger Ribonucleic Acid) tumor vaccine for treating mouse liver cancer, which is prepared by the following steps: S1, specific neoantigen prediction: carrying out bioinformatics analysis on a next-generation sequencing database of tumor patients in the hospital, and selecting tumor specific neoantigens through the following steps; s11, low-quality readings are removed through a filtering step; s12, detecting single nucleotide variation by using a Mutect method and a VarScan method; s13, annotating missense mutation by using ANNOVAR software; in-vivo and in-vitro experiments prove that the vaccine has a remarkable anti-tumor effect, is designed and synthesized aiming at a newly screened new antigen mutation sequence and has high specificity and pertinence, and experimental results show that the vaccine can remarkably improve immune response of specific CTLs cells, induce T cell response of new antigen specificity, and has a good anti-tumor effect in a tumor-bearing mouse model. The vaccine has a remarkable inhibiting effect on tumor growth, and the problems in the prior art are solved through the technical scheme.

Embodiments relate to novel vaccines against human papillomavirus (HPV) and HPV-related diseases, including multiple types of cancers. The HPV vaccines are composed of anti-human dendritic cell (DC) surface receptor antibodies, including CD40, and E6 / 7 proteins of HPV16 and 18. The technology described is not limited to making vaccines against HPV16- and HPV18-related diseases and can be applied to making vaccines carrying E6 / 7 from any type of HPV. The HPV vaccines described can target DCs, major and professional antigen presenting cells (APCs), and can induce and activate potent HPV E6 / 7-specific and strong CD4+ and CD8+ T cell responses. The HPV vaccines can be used for the prevention of HPV infection and HPV-related diseases as well as for the treatment of HPV-related diseases, including cancers.

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 present invention relates to the treatment of Tauopathies. In this study, the inventors worked on an optimized treatment of Tauopathies, including AD and primary Tauopathies. Previously, the inventors evidenced that Tau pathology is associated with deleterious T-cell-mediated processes that contribute to promote Tau-related detrimental neuroinflammation and cognitive deficits. Considering the unique capacity of immunosuppressive Tregs to inhibit both CD4+ and CD8+ T cell responses, the inventors raise the hypothesis that amplifying Tregs may allow controlling Tau-driven T-cell-mediated detrimental processes in the course of AD and other Tauopathies. They thus evaluated preclinically the impact on disease progression of an optimized IL-2-based Treg-targeting immunomodulatory treatment in the THY-Tau22 mouse model of Tauopathy. They chronically treated THY-Tau22 mice with an optimized IL-2-based treatment, i.e. complexes of IL-2 and anti-IL-2 antibodies (termed herein IL-2C) in order to modulate Tau-associated detrimental T cell responses. Their data supports that this treatment amplifies Tregs more efficiently and selectively than "regular" low dose IL-2 treatment. Furthermore, they hereby showed that IL-2C has a beneficial effect on cognitive deficits since treated THY-Tau22 mice tend to acquire and retain spatial information more potently than untreated littermates. Thus, the invention relates to an IL-2 / anti-IL-2 complex (IL-2C) for use in the treatment of Tauopathies.

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 methods for generating an immune response for treating or preventing hepatitis B virus infection. The present disclosure also relates to methods for generating MHC-E and / or MHC-II restricted CD8+ T cells for treating or preventing hepatitis B virus infection.

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 peptide-based vaccines for inducing immune response and production methods and uses thereof.SOLUTION: The present disclosure relates to novel peptide-based vaccines, methods of manufacturing the novel peptide-based vaccines and uses thereof for delivering peptide antigens to induce an immune response, and in particular a T cell response to a subject. The present inventors have developed novel compositions and methods of manufacturing peptide-based vaccines that overcome at least one of the limitations of current peptide-based vaccine approaches. The novel peptide-based vaccine compositions and methods of manufacturing disclosed herein account for the variability in the physical and chemical properties of peptide antigens and are therefore generalizable for any peptide antigen.SELECTED DRAWING: None

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.

The present invention provides a recombinant vaccinia virus that simultaneously expresses the extracellular segment of the S gene of the new coronavirus and the full-length segment of the N gene. The present invention also provides an immunization kit containing the recombinant vaccinia virus, and a DNA vector expressing the extracellular segment of the S gene of the new coronavirus and a DNA vector expressing the full-length segment of the N gene of the new coronavirus as a composite vaccine. By using the three vaccines in the composite vaccine provided by the present invention, the sequential inoculation at 0, 2, and 4 weeks can induce experimental animals to produce CD4, CD8 cell responses specific to the N, S1, and S2 proteins of the new coronavirus, and the CD8T cell response is higher than the CD4T cell response, the induced T cell immunity can last for at least 3 months, and the binding antibody lasts for 6 months without a significant decrease, indicating that the composite vaccine can induce a lasting immune response to SARS-CoV-2, and the neutralizing antibodies induced by the vaccine have cross-reactive activity, which can prevent infection of multiple variants of the new coronavirus to a certain extent.

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.

The present invention relates to universal sarbecovirus vaccines that specifically express an interferon. This live universal sarbecovirus vaccine elicits mucosal immunity and heterotypic immunity against various sarbecoviruses, including SARS-CoV-1, SARS-CoV-2, and its variants. Interferon directly encoded from the genome of the live universal sarbecovirus overrides the virus-induced “delayed type-I interferon”, resulting in enhancement of mucosal T cell responses. The present invention further relates to uses of the vaccines for the preparation of pharmaceutical compositions, methods of treating or preventing viral infections, and kits comprising the vaccines.

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.

The invention relates to an epitope polypeptide of cryptosporidium parvum targeting CD4 + T cells and application of the epitope polypeptide. The amino acid sequence of the epitope polypeptide is shown as SEQ ID NO.1; the epitope polypeptide is a combined long epitope polypeptide of cryptosporidium parvum Gp40 / 15 protein, Gp900 protein and CSL protein; the epitope polypeptide can be applied to a vaccine for preventing or treating cryptosporidiosis parvum, and after a mouse is immunized by the vaccine, not only can CD8 + T cell immune response of the mouse be obviously stimulated, but also stronger CD4 + T cell response is induced to be generated, and the mouse can be induced to generate multifunctional T cells related to an immune protection effect; the levels of IFN-gamma, TNF-alpha and IL-2 generated by multifunctional T cells induced by a long polypeptide immune group have extremely significant differences (P is less than 0.01) compared with various negative controls, which indicates that the long polypeptide epitope vaccine has corresponding biological immunological activity and becomes a novel cryptosporidium parvum infection resistant T cell epitope vaccine or an immunodominance T cell epitope-based mRNA vaccine.

This disclosure relates to the field of RNA to prevent or treat coronavirus infection. In particular, the present disclosure relates to methods and agents for vaccination against coronavirus infection and inducing effective coronavirus antigen-specific immune responses such as antibody and / or T cell responses. Specifically, in one embodiment, the present disclosure relates to methods comprising administering to a subject RNA encoding a peptide or protein comprising an epitope of SARS-CoV-2 spike protein (S protein) for inducing an immune response against coronavirus S protein, in particular S protein of SARS-CoV-2, in the subject, i.e., vaccine RNA encoding vaccine antigen.