# US 10,766,932 B2 · Multiple antigen presenting immunogenic composition, and methods and uses thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,766,932 B2 - Document ID: US10766932B2 - Status: Granted - Kind: B2 - Application number: 14/116,402 - Filed: 2012-05-11 - Published: 2014-06-05 - Granted: 2020-09-08 - Earliest claimed: 2011-05-11 - Assignees: Children's Medical Center Corporation - Applicants: Richard Malley; Yingjie Lu; Fan Zhang - Inventors: Richard Malley; Yingjie Lu; Fan Zhang - Web page: https://patentgrep.com/patent/US10766932B2 ## CPC - C07K 14/31: from Staphylococcus (G) - A61K 39/092: {Streptococcus} - A61K 39/385: Haptens or antigens, bound to carriers - A61K 47/543: {Lipids, e.g. triglycerides; Polyamines, e.g. spermine or spermidine} - A61K 47/557: {the modifying agent being biotin} - A61K 47/61: the organic macromolecular compound being a polysaccharide or a derivative thereof - A61P 31/04: Antibacterial agents - A61K 2039/55505: {Inorganic adjuvants} - A61K 2039/6031: {Proteins} - A61K 2039/6093: {Synthetic polymers, e.g. polyethyleneglycol [PEG], Polymers or copolymers of (D) glutamate and (D) lysine} - A61K 2039/625: {binding through the biotin-streptavidin system or similar} - A61K 2039/627: {characterised by the linker} - A61K 2039/645: {Dendrimers; Multiple antigen peptides} - A61K 2039/70: {Multivalent vaccine} - C07K 2319/00: Fusion polypeptide - C07K 2319/20: containing a tag with affinity for a non-protein ligand - 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 - 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) - 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) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE ## Abstract The present embodiments provide for an immunogenic multiple antigen presenting system comprising a polymer to which antigens are associated by complementary affinity molecules. For example, the polymer can be a polysaccharide, or antigenic polysaccharide, to which protein or peptide antigens from the same or different pathogens are indirectly linked. The present immunogenic compositions can elicit both humoral and cellular immune responses to one or multiple antigens at the same time. ## Claims ### Claim 1 An immunogenic composition comprising an immunologically effective amount of at least one antigenic polysaccharide, an immunologically effective amount of one to ten different peptide or polypeptide antigens, and one to ten different pairs of affinity molecules, wherein each pair comprises a first affinity molecule and a second affinity molecule complementary to the first affinity molecule, wherein in each pair: the first affinity molecule is associated with the at least one antigenic polysaccharide, and the complementary second affinity molecule is covalently attached to one of the peptide or polypeptide antigens to form a fusion protein, and the first affinity molecule non-covalently associates with the complementary second affinity molecule to link the respective peptide or polypeptide antigen and the at least one antigenic polysaccharide; and wherein the immunogenic composition, upon administration to a subject, elicits (i) an immune response to the at least one antigenic polysaccharide, and (ii) an immune response to at least one of the one to ten different peptide or polypeptide antigens, in the subject. ### Claim 2 (depends on 1) The immunogenic composition of claim 1, wherein the first affinity molecule is cross-linked or covalently bonded to the antigenic polysaccharide. ### Claim 3 (depends on 2) The immunogenic composition of claim 2, wherein the first affinity molecule is cross-linked to the antigenic polysaccharide using a cross-linking reagent selected from any in the group consisting of: CDAP (1-cyano-4-dimethylaminopyridinium tetrafluoroborate); EDC (1-Ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride); sodium cyanoborohydride; cyanogen bromide; and ammonium bicarbonate/iodoacetic acid. ### Claim 4 (depends on 1) The immunogenic composition of claim 1, wherein the pair(s) of the affinity molecules is/are each independently selected from the group consisting of: biotin/biotin-binding protein, antibody/antigen, enzyme/substrate, receptor/ligand, metal/metal-binding protein, carbohydrate/carbohydrate binding protein, lipid/lipid-binding protein, and His tag/His tag-binding substance. ### Claim 5 (depends on 1) The immunogenic composition of claim 1, wherein the first affinity molecule is biotin or a derivative or mimic molecule thereof. ### Claim 6 (depends on 1) The immunogenic composition of claim 1, wherein the complementary second affinity molecule is a biotin-binding protein, or an avidin-like protein or a derivative or functional portion thereof. ### Claim 7 (depends on 6) The immunogenic composition of claim 6, wherein the avidin-like protein is selected from the group consisting of: rhizavidin, avidin, streptavidin, and a homologue or derivative thereof. ### Claim 8 (depends on 1) The immunogenic composition of claim 1, wherein the antigenic polysaccharide is a branched chain polysaccharide or a straight chain polysaccharide. ### Claim 9 (depends on 1) The immunogenic composition of claim 1, comprising two to ten different peptide or polypeptide antigens, wherein the peptide or polypeptide antigens are selected from the group consisting of: different peptides or polypeptides; different variants of the same peptide or polypeptide; and different domains or portions of the same peptide or polypeptide. ### Claim 10 (depends on 1) The immunogenic composition of claim 1, further comprising a flexible linker peptide attached to the peptide or polypeptide antigens, wherein the flexible linker peptide attaches the peptide or polypeptide antigens to the complementary second affinity molecule. ### Claim 11 (depends on 1) The immunogenic composition of claim 1, wherein at least one of the peptide or polypeptide antigen is from a pathogenic organism, or a cancer or tumor. ### Claim 12 (depends on 1) The immunogenic composition of claim 1, wherein at least one of the peptide or polypeptide antigens is selected from the group consisting of: tuberculosis antigens; Staphylococcus aureus antigens; Acinetobacter antigens; enteric Gram-negative bacterial antigens; nonenteric Gram-negative bacterial antigens; Gram-positive bacterial antigens; toxoids, toxins or toxin portions; fungal antigens; viral antigens; cancer or tumor antigens; and combinations thereof. ### Claim 13 (depends on 1) The immunogenic composition of claim 1, wherein the antigenic polysaccharide is selected from the group consisting of: polysaccharides, oligosaccharides, or lipopolysaccharides from Gram-positive bacteria; polysaccharides, oligosaccharides, or lipopolysaccharides from Gram-negative bacteria; other bacterial capsular or cell wall polysaccharides; fungal polysaccharides; viral polysaccharides; and polysaccharides derived from cancer or tumor cells. ### Claim 14 (depends on 1) The immunogenic composition of claim 1, further comprising at least one co-stimulation factor associated with the antigenic polysaccharide or at least one of the peptide or polypeptide antigens. ### Claim 15 (depends on 14) The immunogenic composition of claim 14, wherein the co-stimulation factor is selected from the group consisting of: a Toll-like receptor ligand/agonist, a NOD ligand/agonist, and an activator/agonist of an inflammasome. ### Claim 16 (depends on 1) The immunogenic composition of claim 1, further comprising at least one adjuvant. ### Claim 17 (depends on 1) A method for inducing an immune response in a subject to at least one antigen, comprising administering to the subject a composition of claim 1. ### Claim 18 (depends on 17) The method of claim 17, wherein the immune response is an antibody or B cell response. ### Claim 19 (depends on 17) The method of claim 17, wherein the immune response is a CD4+ T cell response, including Th1, Th2, or Th17 response, or a CD8+ T cell response, or CD4+/CD8+ T cell response. ### Claim 20 (depends on 17) The method of claim 17, wherein the immune response is: an antibody or B cell response; and a T cell response. ### Claim 21 (depends on 17) The method of claim 17, wherein the immune response is to at least one antigenic polysaccharide or at least one peptide or polypeptide antigen. ### Claim 22 (depends on 17) The method of claim 17, wherein the immune response is an antibody or B cell response to at least one antigenic polysaccharide and a CD4+ T cell response, including Th 1, Th2, or Th 17 response, or a CD8+ T cell response, or CD4+/CD8+ T cell response to at least one peptide or polypeptide antigen. ### Claim 23 (depends on 17) The method of claim 17, wherein the immune response is an antibody or B cell response to at least one antigenic polysaccharide, and an antibody or B cell response and a CD4+ T cell response, including Th1, Th2, or Th 17 response, or a CD8+ T cell response, or CD4+/CD8+ T cell response to at least one peptide or polypeptide antigen. ### Claim 24 (depends on 12) The immunogenic composition of claim 12, wherein the enteric Gram-negative bacterial antigens are selected from the group of: E. coli antigens, Salmonella antigens, Enterobacter antigens, Klebsiella antigens, Citrobacter antigens, Serratia antigens, Clostridia antigens, Shigella antigens, Campylobacter antigens, Vibrio cholera antigens, and combinations thereof. ### Claim 25 (depends on 12) The immunogenic composition of claim 12, wherein the nonenteric Gram-negative bacterial antigens are selected from the group of: Pertussis antigens, Meningococcal antigens, Haemophilus antigens, Pseudomonas antigens, and combinations thereof. ### Claim 26 (depends on 12) The immunogenic composition of claim 12, wherein the Gram-positive bacterial antigens are pneumococcal antigens or anthrax antigens. ### Claim 27 (depends on 12) The immunogenic composition of claim 12, wherein the viral antigens are HIV antigens, or seasonal or epidemic influenza antigens. ### Claim 28 (depends on 13) The immunogenic composition of claim 13, wherein the antigenic polysaccharide is selected from the group consisting of: Salmonella typhi Vi capsular polysaccharides; Salmonella polysaccharides; pneumococcal polysaccharides; Haemophili polysaccharides; Meningococcal polysaccharides; Staphylococcus aureus polysaccharides; Bacillus anthracis polysaccharides; Streptococcus polysaccharides; Pseudomonas polysaccharides; Cryptococcus polysaccharides; and viral glycoproteins. ### Claim 29 (depends on 28) The immunogenic composition of claim 28, wherein the antigenic polysaccharide is selected from the group consisting of: Salmonella typhi Vi capsular polysaccharides; pneumococcal capsular polysaccharides; pneumococcal cell wall polysaccharides; Staphylococcus aureus capsular polysaccharides; Haemophilus influenzae Type b (Hib) polysaccharides; Gp A Streptococcus polysaccharides; and Gp B Streptococcus polysaccharides. ### Claim 30 (depends on 1) The immunogenic composition of claim 1, comprising five to ten different peptide or polypeptide antigens, wherein the peptide or polypeptide antigens are selected from the group consisting of: different peptides or polypeptides; different variants of the same peptide or polypeptide; and different domains or portions of the same peptide or polypeptide. ### Claim 31 (depends on 1) The immunogenic composition of claim 1, comprising two to ten different peptide or polypeptide antigens, wherein at least two different peptide or polypeptide antigens are linked to the same antigenic polysaccharide. ### Claim 32 (depends on 1) The immunogenic composition of claim 1, comprising at least two different antigenic polysaccharides and two to ten different peptide or polypeptide antigens, wherein at least two different peptide or polypeptide antigens are each linked to a different antigenic polysaccharide. ### Claim 33 (depends on 1) The immunogenic composition of claim 1, wherein the complementary second affinity molecule is covalently attached to a fusion protein comprising two or more peptide or polypeptide antigens. ### Claim 34 An immunogenic composition comprising: an immunologically effective amount of at least one antigenic polysaccharide, and an immunologically effective amount of one to ten different peptide or polypeptide antigens, wherein the at least one antigenic polysaccharide is cross-linked or covalently bonded to biotin, and the one to ten peptide or polypeptide antigens are associated with at least one rhizavidin peptide, derivative, or functional portion thereof, and wherein the one to ten peptide or polypeptide antigens and the at least one antigenic polysaccharide are linked by a non-covalent, affinity interaction between the biotin and the rhizavidin peptide, derivative, or functional portion thereof; and wherein the immunogenic composition, upon administration to a subject, elicits (i) an immune response to the at least one antigenic polysaccharide, and (ii) an immune response to at least one of the one to ten different peptide or polypeptide antigens, in the subject. ### Claim 35 (depends on 1) The immunogenic composition of claim 1, wherein the immune response to the at least one antigenic polysaccharide and/or to at least one of the one to ten different peptide or polypeptide antigens comprises an antibody or B cell response. ### Claim 36 (depends on 1) The immunogenic composition of claim 1, wherein the immune response to the at least one antigenic polysaccharide and/or to at least one of the one to ten different peptide or polypeptide antigens comprises a T cell response. ### Claim 37 (depends on 1) The immunogenic composition of claim 1, wherein the immune response to the at least one antigenic polysaccharide and/or to at least one of the one to ten different peptide or polypeptide antigens comprises a CD4+ T cell response, including Th1, Th2, or Th17 response, or a CD8+ T cell response, or a CD4+/CD8+ T cell response. ### Claim 38 (depends on 1) The immunogenic composition of claim 1, wherein the immune response to the at least one antigenic polysaccharide and/or to at least one of the one to ten different peptide or polypeptide antigens comprises: an antibody or B cell response; and a T cell response. ### Claim 39 (depends on 1) The immunogenic composition of claim 1, wherein the immunogenic composition, upon administration to a subject, elicits at least (i) an antibody or B cell response to the at least one antigenic polysaccharide, and (ii) an antibody or B cell response to at least one of the one to ten different peptide or polypeptide antigens, in the subject. ### Claim 40 (depends on 1) The immunogenic composition of claim 1, wherein the immunogenic composition, upon administration to a subject, elicits at least (i) an antibody or B cell response to the at least one antigenic polysaccharide, and (ii) an antibody or B cell response and a CD4+ T cell response, including Th1, Th2, or Th17 response, or a CD8+ T cell response, or a CD4+/CD8+ T cell response to at least one of the one to ten different peptide or polypeptide antigen, in the subject. ### Claim 41 (depends on 1) The immunogenic composition of claim 1, wherein the immunogenic composition, upon administration to a subject, elicits at least (i) an antibody or B cell response to the at least one antigenic polysaccharide, and (ii) a CD4+ T cell response, including Th1, Th2, or Th17 response, or a CD8+ T cell response, or a CD4+/CD8+ T cell response to at least one of the one to ten different peptide or polypeptide antigens, in the subject. ### Claim 42 (depends on 17) The method of claim 17, further comprising administering to the subject a therapeutic agent.