NZ556004A - Compositions of influenza viral proteins comprising at least one flagellin and at least one influenza M2 protein - Google Patents
Compositions of influenza viral proteins comprising at least one flagellin and at least one influenza M2 proteinInfo
- Publication number
- NZ556004A NZ556004A NZ556004A NZ55600405A NZ556004A NZ 556004 A NZ556004 A NZ 556004A NZ 556004 A NZ556004 A NZ 556004A NZ 55600405 A NZ55600405 A NZ 55600405A NZ 556004 A NZ556004 A NZ 556004A
- Authority
- NZ
- New Zealand
- Prior art keywords
- seq
- protein
- influenza
- fusion protein
- flagellin
- Prior art date
Links
- 206010022000 influenza Diseases 0.000 title claims abstract description 117
- 239000000203 mixture Substances 0.000 title claims abstract description 114
- 101001039853 Sonchus yellow net virus Matrix protein Proteins 0.000 title claims abstract description 79
- 108010040721 Flagellin Proteins 0.000 title claims abstract description 41
- 108010067390 Viral Proteins Proteins 0.000 title claims description 42
- 108020001507 fusion proteins Proteins 0.000 claims abstract description 166
- 102000037865 fusion proteins Human genes 0.000 claims abstract description 162
- 101100115709 Mus musculus Stfa2 gene Proteins 0.000 claims description 52
- 101100311241 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) STF2 gene Proteins 0.000 claims description 52
- 108010052285 Membrane Proteins Proteins 0.000 claims description 49
- 102000018697 Membrane Proteins Human genes 0.000 claims description 49
- 108090000623 proteins and genes Proteins 0.000 claims description 40
- 238000000034 method Methods 0.000 claims description 35
- 102000004169 proteins and genes Human genes 0.000 claims description 33
- 230000028993 immune response Effects 0.000 claims description 30
- 239000000556 agonist Substances 0.000 claims description 23
- 101150104647 fljB gene Proteins 0.000 claims description 22
- 230000004936 stimulating effect Effects 0.000 claims description 18
- 241000588724 Escherichia coli Species 0.000 claims description 16
- 102000005348 Neuraminidase Human genes 0.000 claims description 15
- 108010006232 Neuraminidase Proteins 0.000 claims description 15
- 241000607124 Salmonella enterica subsp. enterica serovar Muenchen Species 0.000 claims description 13
- 208000037798 influenza B Diseases 0.000 claims description 9
- 208000037799 influenza C Diseases 0.000 claims description 7
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 claims description 5
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 claims description 5
- 210000004899 c-terminal region Anatomy 0.000 claims description 5
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 96
- 108010084333 N-palmitoyl-S-(2,3-bis(palmitoyloxy)propyl)cysteinyl-seryl-lysyl-lysyl-lysyl-lysine Proteins 0.000 description 79
- 102000004196 processed proteins & peptides Human genes 0.000 description 73
- 229920001184 polypeptide Polymers 0.000 description 69
- 150000007523 nucleic acids Chemical group 0.000 description 58
- 230000001717 pathogenic effect Effects 0.000 description 54
- 244000052769 pathogen Species 0.000 description 49
- UPAQRWMRKQCLSD-HTIIIDOHSA-N 2,3-dipalmitoyl-S-glycerylcysteine Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(CSC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCC UPAQRWMRKQCLSD-HTIIIDOHSA-N 0.000 description 45
- 108091028043 Nucleic acid sequence Proteins 0.000 description 44
- 108010038122 S-(2,3-bis(palmitoyloxy)propyl)cysteine Proteins 0.000 description 44
- 210000004027 cell Anatomy 0.000 description 40
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 39
- 102000002689 Toll-like receptor Human genes 0.000 description 38
- 108020000411 Toll-like receptor Proteins 0.000 description 38
- 235000018102 proteins Nutrition 0.000 description 31
- 241000700605 Viruses Species 0.000 description 30
- 125000003275 alpha amino acid group Chemical group 0.000 description 30
- 208000037797 influenza A Diseases 0.000 description 25
- 235000001014 amino acid Nutrition 0.000 description 24
- 239000000872 buffer Substances 0.000 description 23
- 241000699670 Mus sp. Species 0.000 description 22
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 22
- 230000028327 secretion Effects 0.000 description 21
- 241000271566 Aves Species 0.000 description 20
- 102000008228 Toll-like receptor 2 Human genes 0.000 description 20
- 108010060888 Toll-like receptor 2 Proteins 0.000 description 20
- 150000001413 amino acids Chemical class 0.000 description 20
- 101150038062 fliC gene Proteins 0.000 description 20
- 230000003612 virological effect Effects 0.000 description 18
- 101000669460 Homo sapiens Toll-like receptor 5 Proteins 0.000 description 17
- 102100039357 Toll-like receptor 5 Human genes 0.000 description 17
- 239000000427 antigen Substances 0.000 description 17
- 108091007433 antigens Proteins 0.000 description 17
- 102000036639 antigens Human genes 0.000 description 17
- 230000005847 immunogenicity Effects 0.000 description 17
- 241000712461 unidentified influenza virus Species 0.000 description 16
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 15
- 239000000047 product Substances 0.000 description 15
- 238000002965 ELISA Methods 0.000 description 14
- 241001465754 Metazoa Species 0.000 description 14
- 241000283973 Oryctolagus cuniculus Species 0.000 description 14
- 235000019441 ethanol Nutrition 0.000 description 14
- 230000003053 immunization Effects 0.000 description 14
- 208000015181 infectious disease Diseases 0.000 description 14
- 241000282412 Homo Species 0.000 description 13
- 238000002649 immunization Methods 0.000 description 13
- 241000699666 Mus <mouse, genus> Species 0.000 description 12
- 230000000890 antigenic effect Effects 0.000 description 12
- 239000011347 resin Substances 0.000 description 12
- 229920005989 resin Polymers 0.000 description 12
- 239000011780 sodium chloride Substances 0.000 description 12
- 241000712431 Influenza A virus Species 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 11
- 238000010367 cloning Methods 0.000 description 11
- 239000002158 endotoxin Substances 0.000 description 11
- 238000004519 manufacturing process Methods 0.000 description 11
- 230000004044 response Effects 0.000 description 10
- 238000003786 synthesis reaction Methods 0.000 description 10
- 239000002671 adjuvant Substances 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 230000036039 immunity Effects 0.000 description 9
- 239000013598 vector Substances 0.000 description 9
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 8
- 108010058846 Ovalbumin Proteins 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- 230000008878 coupling Effects 0.000 description 8
- 238000010168 coupling process Methods 0.000 description 8
- 238000005859 coupling reaction Methods 0.000 description 8
- 235000018417 cysteine Nutrition 0.000 description 8
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 8
- 239000003446 ligand Substances 0.000 description 8
- 108020004707 nucleic acids Proteins 0.000 description 8
- 102000039446 nucleic acids Human genes 0.000 description 8
- 229940092253 ovalbumin Drugs 0.000 description 8
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
- 229960005486 vaccine Drugs 0.000 description 8
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 7
- 238000011725 BALB/c mouse Methods 0.000 description 7
- 241000287828 Gallus gallus Species 0.000 description 7
- 102000004890 Interleukin-8 Human genes 0.000 description 7
- 108090001007 Interleukin-8 Proteins 0.000 description 7
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 7
- 239000007983 Tris buffer Substances 0.000 description 7
- 210000000612 antigen-presenting cell Anatomy 0.000 description 7
- 238000003556 assay Methods 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 7
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 6
- 108090001030 Lipoproteins Proteins 0.000 description 6
- 102000004895 Lipoproteins Human genes 0.000 description 6
- 102000004389 Ribonucleoproteins Human genes 0.000 description 6
- 108010081734 Ribonucleoproteins Proteins 0.000 description 6
- 229930006000 Sucrose Natural products 0.000 description 6
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 6
- 230000003321 amplification Effects 0.000 description 6
- 239000003636 conditioned culture medium Substances 0.000 description 6
- 230000034994 death Effects 0.000 description 6
- 231100000517 death Toxicity 0.000 description 6
- 238000010790 dilution Methods 0.000 description 6
- 239000012895 dilution Substances 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 6
- 238000009396 hybridization Methods 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- 238000003199 nucleic acid amplification method Methods 0.000 description 6
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 6
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 6
- 229940068968 polysorbate 80 Drugs 0.000 description 6
- 229920000053 polysorbate 80 Polymers 0.000 description 6
- 230000003389 potentiating effect Effects 0.000 description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- 210000002966 serum Anatomy 0.000 description 6
- 230000011664 signaling Effects 0.000 description 6
- 239000007790 solid phase Substances 0.000 description 6
- 239000005720 sucrose Substances 0.000 description 6
- PZFZLRNAOHUQPH-GOOVXGPGSA-N (2r)-3-[2,3-di(hexadecanoyloxy)propylsulfanyl]-2-(hexadecanoylamino)propanoic acid Chemical compound CCCCCCCCCCCCCCCC(=O)N[C@H](C(O)=O)CSCC(OC(=O)CCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCC PZFZLRNAOHUQPH-GOOVXGPGSA-N 0.000 description 5
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 5
- -1 amino- Chemical class 0.000 description 5
- 238000003776 cleavage reaction Methods 0.000 description 5
- 230000001419 dependent effect Effects 0.000 description 5
- 230000004927 fusion Effects 0.000 description 5
- 230000002068 genetic effect Effects 0.000 description 5
- 235000011187 glycerol Nutrition 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 102000007863 pattern recognition receptors Human genes 0.000 description 5
- 108010089193 pattern recognition receptors Proteins 0.000 description 5
- 238000010647 peptide synthesis reaction Methods 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 230000004083 survival effect Effects 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- UBCHPRBFMUDMNC-UHFFFAOYSA-N 1-(1-adamantyl)ethanamine Chemical compound C1C(C2)CC3CC2CC1(C(N)C)C3 UBCHPRBFMUDMNC-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 108010002747 Pfu DNA polymerase Proteins 0.000 description 4
- 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 4
- 108700012920 TNF Proteins 0.000 description 4
- 239000007984 Tris EDTA buffer Substances 0.000 description 4
- 102100040247 Tumor necrosis factor Human genes 0.000 description 4
- 208000036142 Viral infection Diseases 0.000 description 4
- 229940037003 alum Drugs 0.000 description 4
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 description 4
- 229960003805 amantadine Drugs 0.000 description 4
- 150000003862 amino acid derivatives Chemical class 0.000 description 4
- 230000005875 antibody response Effects 0.000 description 4
- 231100000673 dose–response relationship Toxicity 0.000 description 4
- 235000013601 eggs Nutrition 0.000 description 4
- VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 230000002163 immunogen Effects 0.000 description 4
- 229930027917 kanamycin Natural products 0.000 description 4
- 229960000318 kanamycin Drugs 0.000 description 4
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 4
- 229930182823 kanamycin A Natural products 0.000 description 4
- 229920006008 lipopolysaccharide Polymers 0.000 description 4
- 239000011159 matrix material Substances 0.000 description 4
- 239000013642 negative control Substances 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 108091008146 restriction endonucleases Proteins 0.000 description 4
- 229960000888 rimantadine Drugs 0.000 description 4
- 230000007017 scission Effects 0.000 description 4
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 241000894007 species Species 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000005382 thermal cycling Methods 0.000 description 4
- 230000009385 viral infection Effects 0.000 description 4
- 210000002845 virion Anatomy 0.000 description 4
- 108010002375 2,3-bis(palmitoyloxy)-2-propyl-1-palmitoylcysteine Proteins 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
- 241000713196 Influenza B virus Species 0.000 description 3
- 241000713297 Influenza C virus Species 0.000 description 3
- 208000002979 Influenza in Birds Diseases 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 108010076504 Protein Sorting Signals Proteins 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 206010064097 avian influenza Diseases 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000010276 construction Methods 0.000 description 3
- 210000004443 dendritic cell Anatomy 0.000 description 3
- 238000010511 deprotection reaction Methods 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 235000019329 dioctyl sodium sulphosuccinate Nutrition 0.000 description 3
- 229960000878 docusate sodium Drugs 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 230000021995 interleukin-8 production Effects 0.000 description 3
- 238000005342 ion exchange Methods 0.000 description 3
- 239000007922 nasal spray Substances 0.000 description 3
- 230000003472 neutralizing effect Effects 0.000 description 3
- VSZGPKBBMSAYNT-RRFJBIMHSA-N oseltamivir Chemical compound CCOC(=O)C1=C[C@@H](OC(CC)CC)[C@H](NC(C)=O)[C@@H](N)C1 VSZGPKBBMSAYNT-RRFJBIMHSA-N 0.000 description 3
- 229960003752 oseltamivir Drugs 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 230000019491 signal transduction Effects 0.000 description 3
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 3
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- ARAIBEBZBOPLMB-UFGQHTETSA-N zanamivir Chemical compound CC(=O)N[C@@H]1[C@@H](N=C(N)N)C=C(C(O)=O)O[C@H]1[C@H](O)[C@H](O)CO ARAIBEBZBOPLMB-UFGQHTETSA-N 0.000 description 3
- 229960001028 zanamivir Drugs 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 2
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 2
- 102100036826 Aldehyde oxidase Human genes 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 102000014914 Carrier Proteins Human genes 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 206010053567 Coagulopathies Diseases 0.000 description 2
- 108091035707 Consensus sequence Proteins 0.000 description 2
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 2
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- 101000928314 Homo sapiens Aldehyde oxidase Proteins 0.000 description 2
- 101000763579 Homo sapiens Toll-like receptor 1 Proteins 0.000 description 2
- 101000763537 Homo sapiens Toll-like receptor 10 Proteins 0.000 description 2
- 101000669447 Homo sapiens Toll-like receptor 4 Proteins 0.000 description 2
- 108090000862 Ion Channels Proteins 0.000 description 2
- 102000004310 Ion Channels Human genes 0.000 description 2
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 101100481579 Mus musculus Tlr11 gene Proteins 0.000 description 2
- 101100481580 Mus musculus Tlr12 gene Proteins 0.000 description 2
- 208000000112 Myalgia Diseases 0.000 description 2
- 102000011931 Nucleoproteins Human genes 0.000 description 2
- 108010061100 Nucleoproteins Proteins 0.000 description 2
- 241000235648 Pichia Species 0.000 description 2
- 101100120241 Salmonella muenchen fliC gene Proteins 0.000 description 2
- 101900195698 Salmonella typhimurium Flagellin Proteins 0.000 description 2
- 229920002684 Sepharose Polymers 0.000 description 2
- 238000012300 Sequence Analysis Methods 0.000 description 2
- 241000282887 Suidae Species 0.000 description 2
- 241000282898 Sus scrofa Species 0.000 description 2
- 102100027010 Toll-like receptor 1 Human genes 0.000 description 2
- 102100027009 Toll-like receptor 10 Human genes 0.000 description 2
- 102100039360 Toll-like receptor 4 Human genes 0.000 description 2
- 159000000021 acetate salts Chemical class 0.000 description 2
- 230000033289 adaptive immune response Effects 0.000 description 2
- 239000003443 antiviral agent Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 108091008324 binding proteins Proteins 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000012412 chemical coupling Methods 0.000 description 2
- YTRQFSDWAXHJCC-UHFFFAOYSA-N chloroform;phenol Chemical compound ClC(Cl)Cl.OC1=CC=CC=C1 YTRQFSDWAXHJCC-UHFFFAOYSA-N 0.000 description 2
- 230000035602 clotting Effects 0.000 description 2
- 230000021615 conjugation Effects 0.000 description 2
- 229940009976 deoxycholate Drugs 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 108010003342 flaB flagellin Proteins 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000012537 formulation buffer Substances 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 230000000984 immunochemical effect Effects 0.000 description 2
- 230000015788 innate immune response Effects 0.000 description 2
- 230000031146 intracellular signal transduction Effects 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 239000007927 intramuscular injection Substances 0.000 description 2
- 231100000518 lethal Toxicity 0.000 description 2
- 230000001665 lethal effect Effects 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000001617 migratory effect Effects 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- DAZSWUUAFHBCGE-KRWDZBQOSA-N n-[(2s)-3-methyl-1-oxo-1-pyrrolidin-1-ylbutan-2-yl]-3-phenylpropanamide Chemical compound N([C@@H](C(C)C)C(=O)N1CCCC1)C(=O)CCC1=CC=CC=C1 DAZSWUUAFHBCGE-KRWDZBQOSA-N 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 239000011886 peripheral blood Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 230000002516 postimmunization Effects 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 238000002953 preparative HPLC Methods 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 238000004007 reversed phase HPLC Methods 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 238000003118 sandwich ELISA Methods 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000010257 thawing Methods 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 230000001960 triggered effect Effects 0.000 description 2
- 238000002255 vaccination Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 230000004580 weight loss Effects 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- DIGQNXIGRZPYDK-WKSCXVIASA-N (2R)-6-amino-2-[[2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-[[(2R,3S)-2-[[2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S,3S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2R)-2-[[2-[[2-[[2-[(2-amino-1-hydroxyethylidene)amino]-3-carboxy-1-hydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1,5-dihydroxy-5-iminopentylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]hexanoic acid Chemical compound C[C@@H]([C@@H](C(=N[C@@H](CS)C(=N[C@@H](C)C(=N[C@@H](CO)C(=NCC(=N[C@@H](CCC(=N)O)C(=NC(CS)C(=N[C@H]([C@H](C)O)C(=N[C@H](CS)C(=N[C@H](CO)C(=NCC(=N[C@H](CS)C(=NCC(=N[C@H](CCCCN)C(=O)O)O)O)O)O)O)O)O)O)O)O)O)O)O)N=C([C@H](CS)N=C([C@H](CO)N=C([C@H](CO)N=C([C@H](C)N=C(CN=C([C@H](CO)N=C([C@H](CS)N=C(CN=C(C(CS)N=C(C(CC(=O)O)N=C(CN)O)O)O)O)O)O)O)O)O)O)O)O DIGQNXIGRZPYDK-WKSCXVIASA-N 0.000 description 1
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- ORILYTVJVMAKLC-UHFFFAOYSA-N Adamantane Natural products C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 1
- 229920000856 Amylose Polymers 0.000 description 1
- 108010032595 Antibody Binding Sites Proteins 0.000 description 1
- 108020000946 Bacterial DNA Proteins 0.000 description 1
- 108010077805 Bacterial Proteins Proteins 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- 101710132601 Capsid protein Proteins 0.000 description 1
- 108091006146 Channels Proteins 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 238000011765 DBA/2 mouse Methods 0.000 description 1
- 102000012410 DNA Ligases Human genes 0.000 description 1
- 108010061982 DNA Ligases Proteins 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 108700022810 Drosophila Hsc70-3 Proteins 0.000 description 1
- 208000004739 Egg Hypersensitivity Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 101710154606 Hemagglutinin Proteins 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101000826116 Homo sapiens Single-stranded DNA-binding protein 3 Proteins 0.000 description 1
- 101000831496 Homo sapiens Toll-like receptor 3 Proteins 0.000 description 1
- 101000669406 Homo sapiens Toll-like receptor 6 Proteins 0.000 description 1
- 101000669402 Homo sapiens Toll-like receptor 7 Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 108091058560 IL8 Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010022005 Influenza viral infections Diseases 0.000 description 1
- 102000019223 Interleukin-1 receptor Human genes 0.000 description 1
- 108050006617 Interleukin-1 receptor Proteins 0.000 description 1
- 108010055717 JNK Mitogen-Activated Protein Kinases Proteins 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 108010006444 Leucine-Rich Repeat Proteins Proteins 0.000 description 1
- 102000003960 Ligases Human genes 0.000 description 1
- 108090000364 Ligases Proteins 0.000 description 1
- 239000006142 Luria-Bertani Agar Substances 0.000 description 1
- 102000043136 MAP kinase family Human genes 0.000 description 1
- 108091054455 MAP kinase family Proteins 0.000 description 1
- 101710199771 Matrix protein 1 Proteins 0.000 description 1
- 101710199769 Matrix protein 2 Proteins 0.000 description 1
- 102000003792 Metallothionein Human genes 0.000 description 1
- 108090000157 Metallothionein Proteins 0.000 description 1
- 102100037808 Mitogen-activated protein kinase 8 Human genes 0.000 description 1
- 102000016943 Muramidase Human genes 0.000 description 1
- 108010014251 Muramidase Proteins 0.000 description 1
- 241000282339 Mustela Species 0.000 description 1
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
- 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 241000712464 Orthomyxoviridae Species 0.000 description 1
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 1
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 108010093965 Polymyxin B Proteins 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 208000034809 Product contamination Diseases 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 101710194807 Protective antigen Proteins 0.000 description 1
- 101710176177 Protein A56 Proteins 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
- 101000697856 Rattus norvegicus Bile acid-CoA:amino acid N-acyltransferase Proteins 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 201000003176 Severe Acute Respiratory Syndrome Diseases 0.000 description 1
- 102100023008 Single-stranded DNA-binding protein 3 Human genes 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 229940124615 TLR 7 agonist Drugs 0.000 description 1
- 229940124614 TLR 8 agonist Drugs 0.000 description 1
- 102100024324 Toll-like receptor 3 Human genes 0.000 description 1
- 102100039387 Toll-like receptor 6 Human genes 0.000 description 1
- 102100039390 Toll-like receptor 7 Human genes 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 108010065667 Viral Matrix Proteins Proteins 0.000 description 1
- BKXQBXXALHYQKZ-NPGUAINNSA-N [3-[(2r)-2-(hexadecanoylamino)-3-methoxy-3-oxopropyl]sulfanyl-2-hexadecanoyloxypropyl] hexadecanoate Chemical compound CCCCCCCCCCCCCCCC(=O)N[C@H](C(=O)OC)CSCC(OC(=O)CCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCC BKXQBXXALHYQKZ-NPGUAINNSA-N 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 230000004721 adaptive immunity Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000007248 cellular mechanism Effects 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 230000000139 costimulatory effect Effects 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 231100000676 disease causative agent Toxicity 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 241001493065 dsRNA viruses Species 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000001163 endosome Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 238000012869 ethanol precipitation Methods 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical group 0.000 description 1
- 244000144992 flock Species 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 238000001641 gel filtration chromatography Methods 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 239000000185 hemagglutinin Substances 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000005745 host immune response Effects 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 230000008076 immune mechanism Effects 0.000 description 1
- 230000008088 immune pathway Effects 0.000 description 1
- 102000028557 immunoglobulin binding proteins Human genes 0.000 description 1
- 108091009323 immunoglobulin binding proteins Proteins 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 210000003000 inclusion body Anatomy 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 229960003971 influenza vaccine Drugs 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000006662 intracellular pathway Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 231100000225 lethality Toxicity 0.000 description 1
- 210000004901 leucine-rich repeat Anatomy 0.000 description 1
- 238000012454 limulus amebocyte lysate test Methods 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 230000002132 lysosomal effect Effects 0.000 description 1
- 239000004325 lysozyme Substances 0.000 description 1
- 229960000274 lysozyme Drugs 0.000 description 1
- 235000010335 lysozyme Nutrition 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000001459 mortal effect Effects 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 231100001160 nonlethal Toxicity 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 239000000816 peptidomimetic Substances 0.000 description 1
- 210000001539 phagocyte Anatomy 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 238000013081 phylogenetic analysis Methods 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920000024 polymyxin B Polymers 0.000 description 1
- 229960005266 polymyxin b Drugs 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 238000002731 protein assay Methods 0.000 description 1
- 239000013014 purified material Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000001932 seasonal effect Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000007974 sodium acetate buffer Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- FRGKKTITADJNOE-UHFFFAOYSA-N sulfanyloxyethane Chemical compound CCOS FRGKKTITADJNOE-UHFFFAOYSA-N 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000011285 therapeutic regimen Methods 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 102000057702 transmembrane signaling receptor Human genes 0.000 description 1
- 108700011013 transmembrane signaling receptor Proteins 0.000 description 1
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000017613 viral reproduction Effects 0.000 description 1
- 230000007923 virulence factor Effects 0.000 description 1
- 239000000304 virulence factor Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
- A61K2039/6031—Proteins
- A61K2039/6075—Viral proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
- A61K2039/6093—Synthetic polymers, e.g. polyethyleneglycol [PEG], Polymers or copolymers of (D) glutamate and (D) lysine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
- C07K2319/74—Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
- C12N2760/00011—Details
- C12N2760/16011—Orthomyxoviridae
- C12N2760/16111—Influenzavirus A, i.e. influenza A virus
- C12N2760/16122—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Virology (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Molecular Biology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Communicable Diseases (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (8)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US63825404P | 2004-12-21 | 2004-12-21 | |
| US63835004P | 2004-12-21 | 2004-12-21 | |
| US64506705P | 2005-01-19 | 2005-01-19 | |
| US65320705P | 2005-02-15 | 2005-02-15 | |
| US66687805P | 2005-03-31 | 2005-03-31 | |
| US68207705P | 2005-05-18 | 2005-05-18 | |
| US74120205P | 2005-11-30 | 2005-11-30 | |
| PCT/US2005/046662 WO2006069262A2 (en) | 2004-12-21 | 2005-12-21 | Compositions of influenza viral proteins and methods of use thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ556004A true NZ556004A (en) | 2010-05-28 |
Family
ID=36272492
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ556004A NZ556004A (en) | 2004-12-21 | 2005-12-21 | Compositions of influenza viral proteins comprising at least one flagellin and at least one influenza M2 protein |
Country Status (9)
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2006206647C1 (en) * | 2005-01-19 | 2011-01-20 | Vaxinnate Corporation | Compositions comprising pathogen-associated molecular patterns and antigens and their use to stimulate an immune response |
| CN106237316A (zh) | 2006-03-07 | 2016-12-21 | 法克斯因内特公司 | 包含血细胞凝集素的组合物、制造其的方法与使用其的方法 |
| US20100068224A1 (en) * | 2006-04-24 | 2010-03-18 | Roberto Crea | Method for Producing Viral Vaccine and Therapeutic Peptide Antigens |
| EP2857038B1 (en) * | 2006-09-18 | 2019-04-10 | The Board of Trustees of the University of Arkansas | Compositions and methods of enhancing immune responses |
| EP1925318A1 (en) * | 2006-11-20 | 2008-05-28 | Paul-Ehrlich-Institut | Recombinant modified vaccinia virus Ankara (MVA)-based vaccine for the avian flu |
| WO2008157419A2 (en) * | 2007-06-13 | 2008-12-24 | The Government Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Immunogenic peptides of influenza virus |
| CA2695399C (en) | 2007-08-02 | 2017-10-17 | Biondvax Pharmaceuticals Ltd. | Multimeric multiepitope influenza vaccines |
| GB0720250D0 (en) | 2007-10-17 | 2007-11-28 | Univ Edinburgh | Immunogenic compositions containing escherichia coli h7 flagella and methods of use thereof |
| WO2009062348A1 (fr) * | 2007-11-14 | 2009-05-22 | Institute Of Microbiology, Chinese Academy Of Sciences | Procédés d'inhibition d'une infection par le virus de la grippe et leurs médicaments |
| WO2009128950A2 (en) | 2008-04-18 | 2009-10-22 | Vaxinnate Corporation | Deletion mutants of flagellin and methods of use |
| WO2010115229A1 (en) | 2009-04-09 | 2010-10-14 | The University Of Melbourne | Immunogenic composition and uses thereof |
| MX348663B (es) * | 2009-09-08 | 2017-05-26 | Inst Tecnologico Estudios Superiores Monterrey | Proceso de producción de una vacuna recombinante, dicha vacuna expresable en cepas de escherichia coli y su uso para combatir la influenza a h1ni1 brote 2009. |
| JP2013516469A (ja) * | 2010-01-06 | 2013-05-13 | ヴァクシネイト コーポレイション | 高齢者に保護免疫を提供するための方法及び組成物 |
| JP6242050B2 (ja) | 2010-01-21 | 2017-12-06 | ザ ボード オブ トラスティーズ オブ ザ ユニバーシティ オブ アーカンソー | 免疫応答を増強するワクチンベクターおよび方法 |
| JP2013523096A (ja) * | 2010-03-26 | 2013-06-17 | エマージェント プロダクト デベロップメント ゲイザーズバーグ インコーポレイテッド | インフルエンザマトリックス２タンパク質の外部ドメイン、発現システムおよびそれらの使用 |
| GB201009273D0 (en) * | 2010-06-03 | 2010-07-21 | Glaxosmithkline Biolog Sa | Novel vaccine |
| WO2012037612A1 (en) | 2010-09-22 | 2012-03-29 | The University Of Melbourne | Novel immunostimulatory method |
| AU2011360572B2 (en) | 2011-02-22 | 2017-03-02 | Biondvax Pharmaceuticals Ltd. | Multimeric multiepitope polypeptides in improved seasonal and pandemic influenza vaccines |
| US8932598B2 (en) | 2012-08-28 | 2015-01-13 | Vaxinnate Corporation | Fusion proteins and methods of use |
| EP2914283B1 (en) * | 2012-11-05 | 2020-05-20 | Georgia State University Research Foundation, Inc. | Universal influenza vaccine based on heterologous multiple m2e proteins |
| RU2571944C1 (ru) * | 2014-10-17 | 2015-12-27 | Общество с ограниченной ответственностью "НТфарма" | Противогриппозная вакцина широкого спектра действия против птичьего гриппа а на основе эктодомена белка м2 |
| CA3085377A1 (en) | 2017-12-21 | 2019-06-27 | Ena Therapeutics Pty Ltd | Optimised compounds |
| CA3142501A1 (en) | 2019-06-26 | 2020-12-30 | Axelia Oncology Pty Ltd | Novel molecules |
| EP4395762A1 (en) * | 2021-09-02 | 2024-07-10 | Ena Respiratory Pty Ltd | Formulation |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1688606B (zh) * | 2002-08-12 | 2013-12-25 | 昆士兰医学研究所理事会 | 含有辅助t细胞和b细胞表位的新的免疫原性脂肽 |
| US20040223976A1 (en) * | 2003-03-07 | 2004-11-11 | Elisabetta Bianchi | Influenza virus vaccine |
-
2005
- 2005-12-21 WO PCT/US2005/046662 patent/WO2006069262A2/en active Application Filing
- 2005-12-21 BR BRPI0519705-8A patent/BRPI0519705A2/pt not_active IP Right Cessation
- 2005-12-21 JP JP2007547054A patent/JP2008524261A/ja active Pending
- 2005-12-21 AU AU2005319141A patent/AU2005319141B8/en not_active Ceased
- 2005-12-21 NZ NZ556004A patent/NZ556004A/en not_active IP Right Cessation
- 2005-12-21 CA CA002593746A patent/CA2593746A1/en not_active Abandoned
- 2005-12-21 MX MX2007007586A patent/MX2007007586A/es not_active Application Discontinuation
- 2005-12-21 SG SG201001924-8A patent/SG160424A1/en unknown
- 2005-12-21 EP EP05855253A patent/EP1831259A2/en not_active Withdrawn
-
2010
- 2010-01-07 AU AU2010200048A patent/AU2010200048A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| BRPI0519705A2 (pt) | 2009-03-10 |
| MX2007007586A (es) | 2007-12-10 |
| JP2008524261A (ja) | 2008-07-10 |
| AU2005319141B8 (en) | 2010-03-18 |
| AU2005319141B2 (en) | 2010-02-18 |
| AU2005319141A1 (en) | 2006-06-29 |
| AU2010200048A1 (en) | 2010-01-28 |
| WO2006069262A3 (en) | 2007-02-01 |
| EP1831259A2 (en) | 2007-09-12 |
| SG160424A1 (en) | 2010-04-29 |
| WO2006069262A2 (en) | 2006-06-29 |
| CA2593746A1 (en) | 2006-06-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2005319141B8 (en) | Compositions of influenza viral proteins and methods of use thereof | |
| AU2007224034B2 (en) | Compositions that include hemagglutinin, methods of making and methods of use thereof | |
| US20090162400A1 (en) | Compositions of influenza viral proteins and methods of use thereof | |
| JP6294828B2 (ja) | インフルエンザウイルスワクチンおよびその使用 | |
| AU2009236585B2 (en) | Deletion mutants of flagellin and methods of use | |
| EP2069503B1 (en) | Papaya mosaic virus-based vaccines for influenza | |
| AU2014273173B2 (en) | Influenza virus vaccines and uses thereof | |
| CN106661091B (zh) | 流行性感冒病毒疫苗及其用途 | |
| US20120052082A1 (en) | Cross-protective influenza vaccine | |
| US12397050B2 (en) | Universal mammalian influenza vaccine | |
| Kim et al. | Immunogenicity and efficacy of replication-competent recombinant influenza virus carrying multimeric M2 extracellular domains in a chimeric hemagglutinin conjugate | |
| JP7167088B2 (ja) | インフルエンザウイルスワクチンおよびその使用 | |
| CN101087808A (zh) | 流行性感冒病毒蛋白质的组合物及其使用方法 | |
| HK1173381A (en) | Compositions that include hemagglutinin, methods of making and methods of use thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PSEA | Patent sealed | ||
| RENW | Renewal (renewal fees accepted) | ||
| LAPS | Patent lapsed |