# US 2024/0189415 A1 · Graphene oxide nanoparticles and methods of use for stimulating immune responses > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2024/0189415 A1 - Document ID: US20240189415A1 - Status: Published application - Kind: A1 - Application number: 18/286,191 - Filed: 2022-04-08 - Published: 2024-06-13 - Earliest claimed: 2021-04-08 - Assignees: Georgia State University Research Foundation, Inc. - Applicants: Georgia State University Research Foundation, Inc. - Inventors: Baozhong Wang; Chunhong Dong - Web page: https://patentgrep.com/patent/US20240189415A1 ## CPC - A61K 39/145: Orthomyxoviridae, e.g. influenza virus - A61P 35/00: Antineoplastic agents - A61K 39/12: Viral antigens - A61K 47/59: obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes - A61K 47/6923: {the form being an inorganic particle, e.g. ceramic particles, silica particles, ferrite or synsorb} - A61K 47/6929: {the form being a nanoparticle, e.g. an immuno-nanoparticle} - A61P 31/16: for influenza or rhinoviruses - 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 9/0043: {Nose} - A61K 2039/543: {intranasal} - A61K 2039/55555: {Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers} - A61K 2039/55561: {CpG containing adjuvants; Oligonucleotide containing adjuvants} - A61K 2039/572: {cytotoxic response} - A61K 2039/575: {humoral response} - C12N 2760/16134: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein - C12N 2760/16171: Demonstrated in vivo effect - 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) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - 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 Disclosed are functionalized graphene oxide nanoparticles and methods their use in inhibiting and treating microbial infection. The disclosure herein further provides for methods of making functionalized graphene oxide nanoparticles and said nanoparticles further incorporating microbial antigens for inducing antigen specific immune responses. ## Claims ### Claim 1 A composition comprising i) a functionalized graphene oxide (GO) nanoparticle comprising polyethyleneimine (PEI) (GO-PEI, GP) and ii) a microbial antigen, vaccine, and/or pharmaceutical agent. ### Claim 2 (depends on 1) The composition of claim 1, wherein the functionalized graphene oxide (GO) nanoparticle comprising polyethyleneimine (PEI) (GO-PEI, GP) is PEGylated. ### Claim 3 (depends on 1) The composition of claim 1, wherein the functionalized graphene oxide (GO) nanoparticle forms a nanosheet. ### Claim 4 (depends on 1) The composition of claim 1, wherein the microbial antigen comprises a peptide, polypeptide, protein, inactivated virus, or heat killed virus. ### Claim 5 (depends on 1) The composition of claim 1, wherein the microbial antigen comprises a viral antigen from a virus selected from the group consisting of Herpes Simplex virus-1, Herpes Simplex virus-2, Varicella-Zoster virus, Epstein-Barr virus, Cytomegalovirus, Human Herpes virus-6, Variola virus, Vesicular stomatitis virus, Hepatitis A virus, Hepatitis B virus, Hepatitis C virus, Hepatitis D virus, Hepatitis E virus, Rhinovirus, Coronavirus (including, but not limited to avian coronavirus (IBV), porcine coronavirus HKU15 (PorCoV HKU15), Porcine epidemic diarrhea virus (PEDV), HCoV-229E, HCoV-OC43, HCoV-HKU1, HCoV-NL63, SARS-CoV, SARS-CoV-2 (including, but not limited to the B1.351 variant, B.1.1.7 variant, and P.1 variant), or MERS-CoV), Influenza virus A, Influenza virus B, Measles virus, Polyomavirus, Human Papilomavirus, Respiratory syncytial virus, Adenovirus, Coxsackie virus, Dengue virus, Mumps virus, Poliovirus, Rabies virus, Rous sarcoma virus, Reovirus, Yellow fever virus, Zika virus, Ebola virus, Marburg virus, Lassa fever virus, Eastern Equine Encephalitis virus, Japanese Encephalitis virus, St. Louis Encephalitis virus, Murray Valley fever virus, West Nile virus, Rift Valley fever virus, Rotavirus A, Rotavirus B, Rotavirus C, Sindbis virus, Simian Immunodeficiency virus, Human T-cell Leukemia virus type-1, Hantavirus, Rubella virus, Simian Immunodeficiency virus, Human Immunodeficiency virus type-1, and Human Immunodeficiency virus type-2. ### Claim 6 (depends on 5) The composition of claim 5, wherein the viral antigen comprises a peptide, polypeptide, or protein of an influenza virus hemagglutinin (HA) protein. ### Claim 7 (canceled) ### Claim 8 (canceled) ### Claim 9 (depends on 6) The composition of claim 6, wherein the HA protein comprises a trimeric HA. ### Claim 10 (depends on 5) The composition of claim 5, wherein the viral antigen comprises a peptide, polypeptide, or protein of a coronavirus spike protein or envelope protein; a peptide, polypeptide, or protein of a human immunodeficiency virus (HIV) glycoprotein (gp), envelope protein (Env), or gag protein; a peptide, polypeptide, or protein of a zika virus capsid protein, envelope protein, or premembrane/membrane protein; a peptide, polypeptide, or protein of a dengue virus capsid protein, envelope protein, or premembrane/membrane protein; a peptide, polypeptide, or protein of a Herpes Simplex (HSV)-1 or HSV-2 glycoprotein D or glycoprotein G: a peptide, polypeptide, or protein of a varicella zoster virus (VZV) glycoprotein E; a peptide, polypeptide, or protein of an Epstein-Barr virus (EBV) or Cytomegalovirus (CMV) glycoprotein; a peptide, polypeptide, or protein of a Respiratory synsyctial virus (RSV) G protein; a peptide, polypeptide, or protein of a measles virus hemagglutinin protein or fusion protein; a peptide, polypeptide, or protein of a rabies virus glycoprotein; a peptide, polypeptide, or protein of a rotavirus viral protein 4 or viral protein 7; a peptide, polypeptide, or protein of a hepatitis B virus surface antigen; or a peptide, polypeptide, or protein of a hepatitis C virus E1, E2, or E3 protein. ### Claim 11 (canceled) ### Claim 12 (canceled) ### Claim 13 (canceled) ### Claim 14 (canceled) ### Claim 15 (canceled) ### Claim 16 (canceled) ### Claim 17 (canceled) ### Claim 18 (canceled) ### Claim 19 (canceled) ### Claim 20 (canceled) ### Claim 21 (canceled) ### Claim 22 (canceled) ### Claim 23 (depends on 1) The composition of claim 1, wherein the microbial antigen comprises a bacterial antigen from a bacteria selected from the group consisting of Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacterium bovis strain BCG, BCG substrains, Mycobacterium avium, Mycobacterium intracellular, Mycobacterium africanum, Mycobacterium kansasii, Mycobacterium marinum, Mycobacterium ulcerans, Mycobacterium avium subspecies paratuberculosis, Nocardia asteroides, other Nocardia species, Legionella pneumophila, other Legionella species, Bacillus anthracis, Acetinobacter baumanii, Salmonella typhi, Salmonella enterica, other Salmonella species, Shigella boydii, Shigella dysenteriae, Shigella sonnei, Shigella flexneri, other Shigella species, Yersinia pestis, Pasteurella haemolytica, Pasteurella multocida, other Pasteurella species, Actinobacillus pleuropneumoniae, Listeria monocytogenes, Listeria ivanovii, Brucella abortus, other Brucella species, Cowdria ruminantium, Borrelia burgdorferi, Bordetella avium, Bordetella pertussis, Bordetella bronchiseptica, Bordetella trematum, Bordetella hinzii, Bordetella pteri, Bordetella parapertussis, Bordetella ansorpii other Bordetella species, Burkholderia mallei, Burkholderia psuedomallei, Burkholderia cepacian, Chlamydia pneumoniae, Chlamydia trachomatis, Chlamydia psittaci, Coxiella burnetii, Rickettsial species, Ehrlichia species, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Escherichia coli, Vibrio cholerae, Campylobacter species, Neiserria meningitidis, Neiserria gonorrhea, Pseudomonas aeruginosa, other Pseudomonas species, Haemophilus influenzae, Haemophilus ducreyi, other Hemophilus species, Clostridium tetani, other Clostridium species, Yersinia enterolitica, and other Yersinia species. ### Claim 24 (depends on 1) The composition of claim 1, wherein the pharmaceutical agent comprises zanamivir, oseltamivir, peramivir, baloxavir, midazolam, lorazepam, flumazenil, dexmedetomidine, ketamine, fentanyl, hydromorphone, butorphanol, naloxone, insulin, fluticasone, ciclesonide, budesonide, dupilumab, mometasone, albuterol, reslizumab, zileuton, mepolizumab, omalizumab, and haloperidol. ### Claim 25 (depends on 1) The composition of claim 1, wherein the weight-to-weight ratio of GO-PEI particles to microbial antigen ranging from 10:1 to 1:10. ### Claim 26 (depends on 1) The composition of claim 1, further comprising an adjuvant. ### Claim 27 (depends on 26) The composition of claim 26, wherein the adjuvant comprises CpG oligonucleotide (CpG ODN). ### Claim 28 (depends on 26) The composition of claim 26, wherein the weight-to-weight ratio of GO-PEI particles to microbial antigen to adjuvant comprises 10:5:2.5 or 10:5:1. ### Claim 29 (depends on 1) The composition of claim 1, wherein the combination of a functionalized GO nanoparticle, microbial antigen with or without an adjuvant has a diameter of about 50 to about 300 nm. ### Claim 30 (depends on 1) The composition of claim 1, wherein the composition has a tunable zeta potential. ### Claim 31 (depends on 1) A vaccine comprising the composition of claim 1. ### Claim 32 (depends on 31) A method of inhibiting a microbial infection, treating a microbial infection, inducing an immune response in a subject to a microbial antigen, vaccine, or pharmaceutical antigen, or delivering an antigen, vaccine, and/or pharmaceutical agent to a mucosal surface of a subject comprising administering to a subject at risk of being infected with a microbe or infected with a microbe, the vaccine of claim 31. ### Claim 33 (canceled) ### Claim 34 (canceled) ### Claim 35 (canceled) ### Claim 36 (depends on 32) The method of inducing an immune response of claim 32, wherein the immune response comprises production of IgA antibody, IgG antibody, IL-6 cytokine production, and/or TNF-α production. ### Claim 37 (canceled) ### Claim 38 (canceled) ### Claim 39 A method of making a vaccine to a microbial antigen comprising a. obtaining a graphene oxide (GO) powder; b. sonicating GO flakes in an ice bath until the GO particles are less than 500 nm in diameter using tip ultrasonication; c. adding polyethyleneimine (PEI) and sonicating; d. activating the GO-PEI with EDC; and e. adding the microbial antigen to the activated GO-PEI particles at a GO-PEI to Ag weight-to-weight ratio ranging from 10:1 to 1:10. ### Claim 40 (depends on 39) The method of making a vaccine to a microbial antigen of claim 39, wherein the sonication continues until the GO particles in step b are less than 200 nm in diameter. ### Claim 41 (canceled) ### Claim 42 (depends on 39) The method of making a vaccine to a microbial antigen of claim 39, further comprising PEGylating the GO-PEI particles. ### Claim 43 (depends on 39) The method of making a vaccine to a microbial antigen of claim 39, further comprising co-loading an adjuvant with the microbial antigen onto the GO-PEI nanoparticles. ### Claim 44 (depends on 43) The method of making a vaccine to a microbial antigen of claim 43, wherein the weight-to-weight ratio of GO-PEI particles to microbial antigen to adjuvant comprises 10:5:2.5 or 10:5:1.