# US 10,117,922 B2 · Dengue virus specific multiple HLA binding T cell epitopes for the use of universal vaccine development > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,117,922 B2 - Document ID: US10117922B2 - Status: Granted - Kind: B2 - Application number: 15/310,542 - Filed: 2015-05-11 - Published: 2017-05-04 - Granted: 2018-11-06 - Earliest claimed: 2014-05-13 - Assignees: Emergex Vaccines Holding Ltd. - Applicants: Emergex Vaccines Holding Ltd. - Inventors: Ramila Philip - Web page: https://patentgrep.com/patent/US10117922B2 ## CPC - A61K 39/12: Viral antigens - C07K 14/005: from viruses - C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00) - A61K 2039/55566: {Emulsions, e.g. Freund's adjuvant, MF59} - A61K 2039/572: {cytotoxic response} - A61K 2039/70: {Multivalent vaccine} - C12N 2770/24122: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes - C12N 2770/24134: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein - Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE ## Abstract Dengue Fever (DF) and Dengue Hemorrhagic Fever (DHF) are significant global public health problems and understanding the overall immune response to infection will contribute to appropriate management of the disease and its potentially severe complications. Live attenuated and subunit vaccine candidates, which are under clinical evaluation, induce primarily an antibody response to the virus and minimal cross-reactive T cell responses. Currently, there are no available tools to assess protective T cell responses during infection or post vaccination. Herein, we report novel, naturally processed and presented MHC class I restricted epitopes, a subset of which binds to and activates T cells in both an HLA-A2 and HLA-A24 restricted manner. We show that epitope specific T cells can be activated in vivo in transgenic mice and in vitro in seropositive and seronegative individuals and that these T cells are functional, recognizing peptide pulsed and dengue virus infected cells in a pro-inflammatory and cytotoxic manner. These epitopes have potential as new informational and diagnostic tools to characterize T cell immunity in Dengue virus (DV) infection, and may serve as a universal vaccine candidate complementary to current vaccines in trial. ## Claims ### Claim 1 A method for vaccinating and treating a subject for dengue virus infection comprising (i) administering to said subject a composition comprising at least one peptide, oligopeptide or polypeptide that binds to more than one class I MHC allele or can be processed to bind to more than one class I MHC allele and comprises an epitopic peptide comprising an amino acid sequence of SEQ ID NO 2, in an amount sufficient to induce a CTL response to cells infected with dengue virus and expressing one of the more than one class I MHC alleles; or (ii) administering to said subject a composition comprising at least one peptide, oligopeptide or polypeptide that binds to more than one class I MHC allele or can be processed to bind to more than one class I MHC allele and comprises an epitopic peptide having at least one amino acid difference from the amino acid sequence of SEQ ID NO 2, in an amount sufficient to induce a CTL response to cells infected with dengue virus and expressing one of the more than one class I MHC alleles. ### Claim 2 A method for vaccinating and treating a subject with dengue virus infection said method comprising (i) administering to said subject a composition comprising a polynucleotide comprising a nucleic acid sequence encoding at least one peptide, oligopeptide or polypeptide that binds to more than one class I MHC allele or can be processed to bind to more than one class I MHC allele and comprises the amino acid sequence of SEQ ID NO 2, in an amount sufficient to induce a CTL response to cells infected with dengue virus and expressing one of the more than one class I MHC alleles; or (ii) administering to said subject a composition comprising a polynucleotide comprising a nucleic acid sequence encoding at least one peptide, oligopeptide or polypeptide that binds to more than one class I MHC allele or can be processed to bind to more than one class I MHC allele and comprising an epitopic peptide comprising one amino acid difference from the amino acid sequence of SEQ ID NO 2, in an amount sufficient to induce a CTL response to cells infected with dengue virus and expressing one of the more than one class I MHC alleles. ### Claim 3 A method for generating an immune response ex vivo using T cells from a subject infected with dengue virus, said method comprising: stimulating the production of CTL response for use in passive immunotherapy, wherein said T cells react with at least one peptide, oligopeptide or polypeptide comprising an amino acid sequence of SEQ ID NO 2; or at least one peptide, oligopeptide or polypeptide comprising one amino acid difference from an amino acid sequence of SEQ ID NO 2. ### Claim 4 (depends on 3) The method of claim 3, wherein said T cells for use in passive immunotherapy are generated from autologous or HLA matched subjects. ### Claim 5 A method for assessing or diagnosing an immune response in a subject infected with dengue virus or vaccinated for dengue and related viruses said method comprising: stimulating the production of CTL response, wherein said T cells react with at least one peptide, oligopeptide or polypeptide comprising the amino acid sequence of SEQ ID NO 2; or at least one peptide, oligopeptide or polypeptide comprising one amino acid difference from the amino acid sequence of SEQ ID NO 2. ### Claim 6 A method for vaccinating humans against Dengue virus infection using SEQ ID NO 2 in any delivery system appropriate to generate a vaccine response.