JP2012525134A - インフルエンザ赤血球凝集素の組成物とその使用 - Google Patents
インフルエンザ赤血球凝集素の組成物とその使用 Download PDFInfo
- Publication number
- JP2012525134A JP2012525134A JP2012507784A JP2012507784A JP2012525134A JP 2012525134 A JP2012525134 A JP 2012525134A JP 2012507784 A JP2012507784 A JP 2012507784A JP 2012507784 A JP2012507784 A JP 2012507784A JP 2012525134 A JP2012525134 A JP 2012525134A
- Authority
- JP
- Japan
- Prior art keywords
- ectodomain
- protein
- amino acid
- influenza
- seq
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 127
- 206010022000 influenza Diseases 0.000 title claims abstract description 57
- 101710154606 Hemagglutinin Proteins 0.000 title description 207
- 101710093908 Outer capsid protein VP4 Proteins 0.000 title description 207
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 title description 207
- 101710176177 Protein A56 Proteins 0.000 title description 207
- 239000000185 hemagglutinin Substances 0.000 title description 149
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 158
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 141
- 241000712461 unidentified influenza virus Species 0.000 claims abstract description 132
- 239000012634 fragment Substances 0.000 claims abstract description 124
- 102000036639 antigens Human genes 0.000 claims abstract description 98
- 108091007433 antigens Proteins 0.000 claims abstract description 98
- 239000000427 antigen Substances 0.000 claims abstract description 97
- 229960005486 vaccine Drugs 0.000 claims abstract description 95
- 239000002245 particle Substances 0.000 claims abstract description 70
- 241001515965 unidentified phage Species 0.000 claims abstract description 42
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 30
- 241001465754 Metazoa Species 0.000 claims abstract description 23
- 238000000034 method Methods 0.000 claims abstract description 23
- 230000003067 hemagglutinative effect Effects 0.000 claims abstract description 16
- 230000002265 prevention Effects 0.000 claims abstract description 9
- 239000003814 drug Substances 0.000 claims abstract description 5
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 170
- 235000001014 amino acid Nutrition 0.000 claims description 142
- 235000018102 proteins Nutrition 0.000 claims description 137
- 150000001413 amino acids Chemical class 0.000 claims description 97
- 230000035931 haemagglutination Effects 0.000 claims description 55
- 241000712431 Influenza A virus Species 0.000 claims description 43
- 101710132601 Capsid protein Proteins 0.000 claims description 41
- 101710094648 Coat protein Proteins 0.000 claims description 41
- 102100021181 Golgi phosphoprotein 3 Human genes 0.000 claims description 41
- 101710125418 Major capsid protein Proteins 0.000 claims description 41
- 101710141454 Nucleoprotein Proteins 0.000 claims description 41
- 101710083689 Probable capsid protein Proteins 0.000 claims description 41
- 210000003743 erythrocyte Anatomy 0.000 claims description 28
- 125000003277 amino group Chemical group 0.000 claims description 26
- 239000002671 adjuvant Substances 0.000 claims description 25
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 21
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims description 19
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 19
- 230000003053 immunization Effects 0.000 claims description 17
- 238000002649 immunization Methods 0.000 claims description 17
- 241000252870 H3N2 subtype Species 0.000 claims description 15
- 230000003612 virological effect Effects 0.000 claims description 15
- 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 claims description 14
- 125000000539 amino acid group Chemical group 0.000 claims description 12
- 241000713196 Influenza B virus Species 0.000 claims description 11
- 241001534160 Escherichia virus Qbeta Species 0.000 claims description 9
- 108020003175 receptors Proteins 0.000 claims description 7
- 102000005962 receptors Human genes 0.000 claims description 7
- 241001672158 Acinetobacter phage AP205 Species 0.000 claims description 6
- 241000831652 Salinivibrio sharmensis Species 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 3
- 108090000371 Esterases Proteins 0.000 claims description 2
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 2
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims description 2
- OFHCOWSQAMBJIW-AVJTYSNKSA-N alfacalcidol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C OFHCOWSQAMBJIW-AVJTYSNKSA-N 0.000 claims description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 2
- 230000028993 immune response Effects 0.000 abstract description 14
- 230000005875 antibody response Effects 0.000 abstract description 11
- 230000009385 viral infection Effects 0.000 abstract description 5
- 230000005180 public health Effects 0.000 abstract description 3
- CTMZLDSMFCVUNX-VMIOUTBZSA-N cytidylyl-(3'->5')-guanosine Chemical group O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@H](OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=C(C(N=C(N)N3)=O)N=C2)O)[C@@H](CO)O1 CTMZLDSMFCVUNX-VMIOUTBZSA-N 0.000 description 73
- 241000699670 Mus sp. Species 0.000 description 61
- 208000037797 influenza A Diseases 0.000 description 53
- 241000700605 Viruses Species 0.000 description 50
- 230000014509 gene expression Effects 0.000 description 47
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 42
- 108091034117 Oligonucleotide Proteins 0.000 description 42
- 125000003729 nucleotide group Chemical group 0.000 description 36
- 239000002773 nucleotide Substances 0.000 description 32
- 230000003308 immunostimulating effect Effects 0.000 description 30
- 239000013612 plasmid Substances 0.000 description 30
- 150000007523 nucleic acids Chemical class 0.000 description 29
- 210000004027 cell Anatomy 0.000 description 28
- 102000039446 nucleic acids Human genes 0.000 description 28
- 108020004707 nucleic acids Proteins 0.000 description 28
- 108020004414 DNA Proteins 0.000 description 23
- 101900159346 Influenza A virus Hemagglutinin Proteins 0.000 description 22
- 210000002966 serum Anatomy 0.000 description 22
- 208000015181 infectious disease Diseases 0.000 description 21
- 239000000243 solution Substances 0.000 description 21
- 231100000518 lethal Toxicity 0.000 description 18
- 230000001665 lethal effect Effects 0.000 description 18
- 238000010367 cloning Methods 0.000 description 17
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 16
- 239000000126 substance Substances 0.000 description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 15
- 238000003556 assay Methods 0.000 description 15
- 238000000746 purification Methods 0.000 description 15
- 241000588724 Escherichia coli Species 0.000 description 14
- 241000699666 Mus <mouse, genus> Species 0.000 description 14
- 241001500351 Influenzavirus A Species 0.000 description 13
- 210000000234 capsid Anatomy 0.000 description 13
- 230000001965 increasing effect Effects 0.000 description 13
- 102000004196 processed proteins & peptides Human genes 0.000 description 13
- 230000002776 aggregation Effects 0.000 description 12
- 238000002474 experimental method Methods 0.000 description 12
- 239000000178 monomer Substances 0.000 description 12
- 230000001681 protective effect Effects 0.000 description 12
- 238000012360 testing method Methods 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 11
- 229960003971 influenza vaccine Drugs 0.000 description 11
- 238000004519 manufacturing process Methods 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 102000053602 DNA Human genes 0.000 description 10
- 108091081548 Palindromic sequence Proteins 0.000 description 10
- 230000000890 antigenic effect Effects 0.000 description 10
- 230000005847 immunogenicity Effects 0.000 description 10
- 230000002458 infectious effect Effects 0.000 description 10
- 150000004713 phosphodiesters Chemical class 0.000 description 10
- 230000003362 replicative effect Effects 0.000 description 10
- 241000287828 Gallus gallus Species 0.000 description 9
- 229940037003 alum Drugs 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 235000013330 chicken meat Nutrition 0.000 description 9
- 102000037865 fusion proteins Human genes 0.000 description 9
- 108020001507 fusion proteins Proteins 0.000 description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
- 230000003993 interaction Effects 0.000 description 9
- 231100000636 lethal dose Toxicity 0.000 description 9
- 230000003252 repetitive effect Effects 0.000 description 9
- 230000004083 survival effect Effects 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 8
- MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 8
- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 8
- 239000007995 HEPES buffer Substances 0.000 description 8
- 241000238631 Hexapoda Species 0.000 description 8
- 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 Chemical class 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 8
- 239000002299 complementary DNA Substances 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
- 230000004927 fusion Effects 0.000 description 8
- 229940029575 guanosine Drugs 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 229920001184 polypeptide Polymers 0.000 description 8
- WCMOHMXWOOBVMZ-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 6-[3-(2,5-dioxopyrrol-1-yl)propanoylamino]hexanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCCCCNC(=O)CCN1C(=O)C=CC1=O WCMOHMXWOOBVMZ-UHFFFAOYSA-N 0.000 description 7
- 238000002965 ELISA Methods 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 238000005054 agglomeration Methods 0.000 description 7
- 230000000735 allogeneic effect Effects 0.000 description 7
- 239000000499 gel Substances 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 239000004971 Cross linker Substances 0.000 description 6
- -1 tripeptides Proteins 0.000 description 6
- 241000282412 Homo Species 0.000 description 5
- 229920002684 Sepharose Polymers 0.000 description 5
- 238000004220 aggregation Methods 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical class NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 5
- 125000000524 functional group Chemical group 0.000 description 5
- 208000037798 influenza B Diseases 0.000 description 5
- 229920002401 polyacrylamide Polymers 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 108091008146 restriction endonucleases Proteins 0.000 description 5
- 229920002477 rna polymer Polymers 0.000 description 5
- 238000001542 size-exclusion chromatography Methods 0.000 description 5
- 238000004448 titration Methods 0.000 description 5
- 239000013598 vector Substances 0.000 description 5
- 241000701533 Escherichia virus T4 Species 0.000 description 4
- 102000009123 Fibrin Human genes 0.000 description 4
- 108010073385 Fibrin Proteins 0.000 description 4
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 4
- 108091008874 T cell receptors Proteins 0.000 description 4
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
- 108010067390 Viral Proteins Proteins 0.000 description 4
- 210000004899 c-terminal region Anatomy 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 238000010790 dilution Methods 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- 239000013604 expression vector Substances 0.000 description 4
- 229950003499 fibrin Drugs 0.000 description 4
- 230000001939 inductive effect Effects 0.000 description 4
- 230000000813 microbial effect Effects 0.000 description 4
- 238000010172 mouse model Methods 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- 238000004806 packaging method and process Methods 0.000 description 4
- 230000036961 partial effect Effects 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 241000701447 unidentified baculovirus Species 0.000 description 4
- 108010040721 Flagellin Proteins 0.000 description 3
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 3
- 102000006992 Interferon-alpha Human genes 0.000 description 3
- 108010047761 Interferon-alpha Proteins 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 102000002067 Protein Subunits Human genes 0.000 description 3
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 3
- 101710194518 T4 protein Proteins 0.000 description 3
- PZBFGYYEXUXCOF-UHFFFAOYSA-N TCEP Chemical compound OC(=O)CCP(CCC(O)=O)CCC(O)=O PZBFGYYEXUXCOF-UHFFFAOYSA-N 0.000 description 3
- 230000036760 body temperature Effects 0.000 description 3
- 238000010382 chemical cross-linking Methods 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 3
- 235000018417 cysteine Nutrition 0.000 description 3
- 210000004443 dendritic cell Anatomy 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 210000003000 inclusion body Anatomy 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- OHDXDNUPVVYWOV-UHFFFAOYSA-N n-methyl-1-(2-naphthalen-1-ylsulfanylphenyl)methanamine Chemical compound CNCC1=CC=CC=C1SC1=CC=CC2=CC=CC=C12 OHDXDNUPVVYWOV-UHFFFAOYSA-N 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- 230000004936 stimulating effect Effects 0.000 description 3
- 239000013638 trimer Substances 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- 241001293113 Anas clypeata Species 0.000 description 2
- 241000272525 Anas platyrhynchos Species 0.000 description 2
- 241000534454 Arenaria interpres Species 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- 108090000565 Capsid Proteins Proteins 0.000 description 2
- 108010024636 Glutathione Proteins 0.000 description 2
- 108010053070 Glutathione Disulfide Proteins 0.000 description 2
- 101900234398 Influenza B virus Hemagglutinin Proteins 0.000 description 2
- 101710180643 Leishmanolysin Proteins 0.000 description 2
- 108010052285 Membrane Proteins Proteins 0.000 description 2
- 102000018697 Membrane Proteins Human genes 0.000 description 2
- 241001529936 Murinae Species 0.000 description 2
- 241001467552 Mycobacterium bovis BCG Species 0.000 description 2
- 108010034546 Serratia marcescens nuclease Proteins 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 2
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 238000003491 array Methods 0.000 description 2
- 229960000190 bacillus calmette–guérin vaccine Drugs 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 230000007123 defense Effects 0.000 description 2
- 238000000326 densiometry Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 238000006073 displacement reaction Methods 0.000 description 2
- 235000013601 eggs Nutrition 0.000 description 2
- 238000005538 encapsulation Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- YPZRWBKMTBYPTK-BJDJZHNGSA-N glutathione disulfide Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@H](C(=O)NCC(O)=O)CSSC[C@@H](C(=O)NCC(O)=O)NC(=O)CC[C@H](N)C(O)=O YPZRWBKMTBYPTK-BJDJZHNGSA-N 0.000 description 2
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 238000013507 mapping Methods 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 238000006386 neutralization reaction Methods 0.000 description 2
- YPZRWBKMTBYPTK-UHFFFAOYSA-N oxidized gamma-L-glutamyl-L-cysteinylglycine Natural products OC(=O)C(N)CCC(=O)NC(C(=O)NCC(O)=O)CSSCC(C(=O)NCC(O)=O)NC(=O)CCC(N)C(O)=O YPZRWBKMTBYPTK-UHFFFAOYSA-N 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000009465 prokaryotic expression Effects 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 238000003259 recombinant expression Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 238000013207 serial dilution Methods 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 238000000547 structure data Methods 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000007501 viral attachment Effects 0.000 description 2
- 230000004580 weight loss Effects 0.000 description 2
- ASWBNKHCZGQVJV-UHFFFAOYSA-N (3-hexadecanoyloxy-2-hydroxypropyl) 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(O)COP([O-])(=O)OCC[N+](C)(C)C ASWBNKHCZGQVJV-UHFFFAOYSA-N 0.000 description 1
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
- DIYPCWKHSODVAP-UHFFFAOYSA-N 1-[3-(2,5-dioxopyrrol-1-yl)benzoyl]oxy-2,5-dioxopyrrolidine-3-sulfonic acid Chemical compound O=C1C(S(=O)(=O)O)CC(=O)N1OC(=O)C1=CC=CC(N2C(C=CC2=O)=O)=C1 DIYPCWKHSODVAP-UHFFFAOYSA-N 0.000 description 1
- CULQNACJHGHAER-UHFFFAOYSA-N 1-[4-[(2-iodoacetyl)amino]benzoyl]oxy-2,5-dioxopyrrolidine-3-sulfonic acid Chemical compound O=C1C(S(=O)(=O)O)CC(=O)N1OC(=O)C1=CC=C(NC(=O)CI)C=C1 CULQNACJHGHAER-UHFFFAOYSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- UFBJCMHMOXMLKC-UHFFFAOYSA-N 2,4-dinitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O UFBJCMHMOXMLKC-UHFFFAOYSA-N 0.000 description 1
- 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 1
- GNTFNWAZTKLCRE-UHFFFAOYSA-N 4-amino-4-bromo-1,3-dihydropyrimidin-2-one Chemical compound NC1(Br)NC(=O)NC=C1 GNTFNWAZTKLCRE-UHFFFAOYSA-N 0.000 description 1
- OZFPSOBLQZPIAV-UHFFFAOYSA-N 5-nitro-1h-indole Chemical compound [O-][N+](=O)C1=CC=C2NC=CC2=C1 OZFPSOBLQZPIAV-UHFFFAOYSA-N 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 101710186708 Agglutinin Proteins 0.000 description 1
- 235000006576 Althaea officinalis Nutrition 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 101100335652 Autographa californica nuclear polyhedrosis virus GP64 gene Proteins 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 102100023321 Ceruloplasmin Human genes 0.000 description 1
- 241000252203 Clupea harengus Species 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 241000557626 Corvus corax Species 0.000 description 1
- 241000186216 Corynebacterium Species 0.000 description 1
- 108091029430 CpG site Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 108010008532 Deoxyribonuclease I Proteins 0.000 description 1
- 102000007260 Deoxyribonuclease I Human genes 0.000 description 1
- 108010053770 Deoxyribonucleases Proteins 0.000 description 1
- 102000016911 Deoxyribonucleases Human genes 0.000 description 1
- SHIBSTMRCDJXLN-UHFFFAOYSA-N Digoxigenin Natural products C1CC(C2C(C3(C)CCC(O)CC3CC2)CC2O)(O)C2(C)C1C1=CC(=O)OC1 SHIBSTMRCDJXLN-UHFFFAOYSA-N 0.000 description 1
- 108010016626 Dipeptides Proteins 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 241000709738 Enterobacteria phage fr Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000672609 Escherichia coli BL21 Species 0.000 description 1
- 101150010917 GP67 gene Proteins 0.000 description 1
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 206010069767 H1N1 influenza Diseases 0.000 description 1
- 101000669460 Homo sapiens Toll-like receptor 5 Proteins 0.000 description 1
- 101710146024 Horcolin Proteins 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 241000134304 Influenza A virus H3N2 Species 0.000 description 1
- 241001500350 Influenzavirus B Species 0.000 description 1
- 229930010555 Inosine Natural products 0.000 description 1
- UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- 241001494920 Larus argentatus Species 0.000 description 1
- 101710189395 Lectin Proteins 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 108090001030 Lipoproteins Proteins 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 241000701076 Macacine alphaherpesvirus 1 Species 0.000 description 1
- 101710179758 Mannose-specific lectin Proteins 0.000 description 1
- 101710150763 Mannose-specific lectin 1 Proteins 0.000 description 1
- 101710150745 Mannose-specific lectin 2 Proteins 0.000 description 1
- 108010090054 Membrane Glycoproteins Proteins 0.000 description 1
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 1
- 102000016943 Muramidase Human genes 0.000 description 1
- 108010014251 Muramidase Proteins 0.000 description 1
- MSFSPUZXLOGKHJ-UHFFFAOYSA-N Muraminsaeure Natural products OC(=O)C(C)OC1C(N)C(O)OC(CO)C1O MSFSPUZXLOGKHJ-UHFFFAOYSA-N 0.000 description 1
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- GOWLTLODGKPXMN-MEKRSRHXSA-N OM-174 Chemical compound O1[C@H](OP(O)(O)=O)[C@H](NC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](O)[C@H](O)[C@H]1CO[C@H]1[C@H](NC(=O)C[C@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCC)[C@@H](O)[C@H](OP(O)(O)=O)[C@@H](CO)O1 GOWLTLODGKPXMN-MEKRSRHXSA-N 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- 108091093037 Peptide nucleic acid Proteins 0.000 description 1
- 108010013639 Peptidoglycan Proteins 0.000 description 1
- 241000286209 Phasianidae Species 0.000 description 1
- 235000014676 Phragmites communis Nutrition 0.000 description 1
- 241000235648 Pichia Species 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 206010049190 Red blood cell agglutination Diseases 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 230000024932 T cell mediated immunity Effects 0.000 description 1
- 230000029662 T-helper 1 type immune response Effects 0.000 description 1
- 241000191971 Tadorna tadornoides Species 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 1
- 102100039357 Toll-like receptor 5 Human genes 0.000 description 1
- 108091034135 Vault RNA Proteins 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 230000010530 Virus Neutralization Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 230000004523 agglutinating effect Effects 0.000 description 1
- 230000004931 aggregating effect Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical group [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- 230000027645 antigenic variation Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 206010064097 avian influenza Diseases 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000002485 combustion reaction Methods 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 230000004041 dendritic cell maturation Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- QONQRTHLHBTMGP-UHFFFAOYSA-N digitoxigenin Natural products CC12CCC(C3(CCC(O)CC3CC3)C)C3C11OC1CC2C1=CC(=O)OC1 QONQRTHLHBTMGP-UHFFFAOYSA-N 0.000 description 1
- SHIBSTMRCDJXLN-KCZCNTNESA-N digoxigenin Chemical compound C1([C@@H]2[C@@]3([C@@](CC2)(O)[C@H]2[C@@H]([C@@]4(C)CC[C@H](O)C[C@H]4CC2)C[C@H]3O)C)=CC(=O)OC1 SHIBSTMRCDJXLN-KCZCNTNESA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 229960002143 fluorescein Drugs 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 102000034238 globular proteins Human genes 0.000 description 1
- 108091005896 globular proteins Proteins 0.000 description 1
- 150000002337 glycosamines Chemical class 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- 150000002357 guanidines Chemical class 0.000 description 1
- 238000010211 hemagglutination inhibition (HI) assay Methods 0.000 description 1
- 235000019514 herring Nutrition 0.000 description 1
- 239000012510 hollow fiber Substances 0.000 description 1
- 230000028996 humoral immune response Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000005965 immune activity Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 230000002584 immunomodulator Effects 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 208000037799 influenza C Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229960003786 inosine Drugs 0.000 description 1
- 230000011488 interferon-alpha production Effects 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 229920006008 lipopolysaccharide Polymers 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 229960000274 lysozyme Drugs 0.000 description 1
- 239000004325 lysozyme Substances 0.000 description 1
- 235000010335 lysozyme Nutrition 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000034217 membrane fusion Effects 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- BSOQXXWZTUDTEL-ZUYCGGNHSA-N muramyl dipeptide Chemical class OC(=O)CC[C@H](C(N)=O)NC(=O)[C@H](C)NC(=O)[C@@H](C)O[C@H]1[C@H](O)[C@@H](CO)O[C@@H](O)[C@@H]1NC(C)=O BSOQXXWZTUDTEL-ZUYCGGNHSA-N 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 150000003014 phosphoric acid esters Chemical class 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 125000005642 phosphothioate group Chemical group 0.000 description 1
- 230000010399 physical interaction Effects 0.000 description 1
- 238000000053 physical method Methods 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920000447 polyanionic polymer Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229940115272 polyinosinic:polycytidylic acid Drugs 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 235000013594 poultry meat Nutrition 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 230000030788 protein refolding Effects 0.000 description 1
- 239000012460 protein solution Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 229960003471 retinol Drugs 0.000 description 1
- 235000020944 retinol Nutrition 0.000 description 1
- 239000011607 retinol Substances 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 238000002922 simulated annealing Methods 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 231100000245 skin permeability Toxicity 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- MKNJJMHQBYVHRS-UHFFFAOYSA-M sodium;1-[11-(2,5-dioxopyrrol-1-yl)undecanoyloxy]-2,5-dioxopyrrolidine-3-sulfonate Chemical compound [Na+].O=C1C(S(=O)(=O)[O-])CC(=O)N1OC(=O)CCCCCCCCCCN1C(=O)C=CC1=O MKNJJMHQBYVHRS-UHFFFAOYSA-M 0.000 description 1
- ULARYIUTHAWJMU-UHFFFAOYSA-M sodium;1-[4-(2,5-dioxopyrrol-1-yl)butanoyloxy]-2,5-dioxopyrrolidine-3-sulfonate Chemical compound [Na+].O=C1C(S(=O)(=O)[O-])CC(=O)N1OC(=O)CCCN1C(=O)C=CC1=O ULARYIUTHAWJMU-UHFFFAOYSA-M 0.000 description 1
- VUFNRPJNRFOTGK-UHFFFAOYSA-M sodium;1-[4-[(2,5-dioxopyrrol-1-yl)methyl]cyclohexanecarbonyl]oxy-2,5-dioxopyrrolidine-3-sulfonate Chemical compound [Na+].O=C1C(S(=O)(=O)[O-])CC(=O)N1OC(=O)C1CCC(CN2C(C=CC2=O)=O)CC1 VUFNRPJNRFOTGK-UHFFFAOYSA-M 0.000 description 1
- MIDXXTLMKGZDPV-UHFFFAOYSA-M sodium;1-[6-(2,5-dioxopyrrol-1-yl)hexanoyloxy]-2,5-dioxopyrrolidine-3-sulfonate Chemical compound [Na+].O=C1C(S(=O)(=O)[O-])CC(=O)N1OC(=O)CCCCCN1C(=O)C=CC1=O MIDXXTLMKGZDPV-UHFFFAOYSA-M 0.000 description 1
- 239000011537 solubilization buffer Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 229940031626 subunit vaccine Drugs 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 201000010740 swine influenza Diseases 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
- 230000009258 tissue cross reactivity Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 238000005829 trimerization reaction Methods 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 230000007502 viral entry Effects 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 239000000277 virosome Substances 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6901—Conjugates being cells, cell fragments, viruses, ghosts, red blood cells or viral vectors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
- A61K47/646—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent the entire peptide or protein drug conjugate elicits an immune response, e.g. conjugate vaccines
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Virology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hematology (AREA)
- Cell Biology (AREA)
- Pulmonology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Toxicology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP09159262.6 | 2009-04-30 | ||
| EP09159262 | 2009-04-30 | ||
| PCT/EP2010/055944 WO2010125202A1 (en) | 2009-04-30 | 2010-04-30 | Influenza hemagglutinin compositions and uses thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2012525134A true JP2012525134A (ja) | 2012-10-22 |
| JP2012525134A5 JP2012525134A5 (enExample) | 2013-06-06 |
Family
ID=42790940
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012507784A Pending JP2012525134A (ja) | 2009-04-30 | 2010-04-30 | インフルエンザ赤血球凝集素の組成物とその使用 |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US20120263743A1 (enExample) |
| EP (1) | EP2424570A1 (enExample) |
| JP (1) | JP2012525134A (enExample) |
| CN (1) | CN102573915B (enExample) |
| AU (1) | AU2010243490A1 (enExample) |
| CA (1) | CA2759873A1 (enExample) |
| NZ (1) | NZ596058A (enExample) |
| SG (1) | SG175382A1 (enExample) |
| WO (1) | WO2010125202A1 (enExample) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106822887A (zh) * | 2017-01-26 | 2017-06-13 | 中国科学院微生物研究所 | 一种流感病毒四价亚单位疫苗及其应用 |
| MA55313A (fr) * | 2019-03-13 | 2022-01-19 | Generation Bio Co | Vecteurs d'adn non viraux et leurs utilisations pour exprimer des agents thérapeutiques du facteur viii |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005517632A (ja) * | 2001-09-14 | 2005-06-16 | サイトス バイオテクノロジー アーゲー | ウィルス様粒子中への免疫賦活物質のパッケージ化：調製法および使用法 |
| US20070042001A1 (en) * | 2005-08-16 | 2007-02-22 | Hawaii Biotech, Inc. | Influenza recombinant subunit vaccine |
| WO2007068747A1 (en) * | 2005-12-14 | 2007-06-21 | Cytos Biotechnology Ag | Immunostimulatory nucleic acid packaged particles for the treatment of hypersensitivity |
| US20070253982A1 (en) * | 2006-03-07 | 2007-11-01 | Langzhou Song | Compositions that include hemagglutinin, methods of making and methods of use thereof |
| JP2009502789A (ja) * | 2005-07-19 | 2009-01-29 | ダウ グローバル テクノロジーズ インコーポレイティド | 組み換えインフルエンザワクチン |
| JP2009513532A (ja) * | 2003-07-10 | 2009-04-02 | サイトス バイオテクノロジー アーゲー | パッケージ化ウイルス様粒子 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU781396B2 (en) * | 1999-07-20 | 2005-05-19 | Morphosys Ag | Novel methods for displaying (poly)peptides/proteins on bacteriophage particles via disulfide bonds |
| US7320793B2 (en) * | 2001-01-19 | 2008-01-22 | Cytos Biotechnology Ag | Molecular antigen array |
| CN100509057C (zh) * | 2001-11-07 | 2009-07-08 | 赛托斯生物技术公司 | 用于治疗骨病的抗原阵列 |
| RU2324704C2 (ru) * | 2002-07-17 | 2008-05-20 | Цитос Байотекнолоджи Аг | Молекулярные массивы антигенов |
| CN101023103A (zh) * | 2004-09-21 | 2007-08-22 | 赛托斯生物技术公司 | 包含ap205外壳蛋白和抗原性多肽的融合蛋白的病毒样颗粒 |
| JP2008513035A (ja) * | 2004-09-21 | 2008-05-01 | サイトス バイオテクノロジー アーゲー | Ａｐ２０５のコートタンパク質と抗原性ポリペプチドとの融合タンパク質を含んでなるウイルス粒子 |
| JP5714799B2 (ja) * | 2005-10-18 | 2015-05-07 | ノババックス インコーポレイテッド | 機能的インフルエンザウイルス様粒子（ｖｌｐ） |
| CU23576A1 (es) * | 2006-02-28 | 2010-09-30 | Ct Ingenieria Genetica Biotech | Antígenos vacunales quiméricos contra el virus de la influenza aviar |
| CN101394864A (zh) * | 2006-03-07 | 2009-03-25 | 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 |
-
2010
- 2010-04-30 AU AU2010243490A patent/AU2010243490A1/en not_active Abandoned
- 2010-04-30 WO PCT/EP2010/055944 patent/WO2010125202A1/en not_active Ceased
- 2010-04-30 CN CN201080019069.9A patent/CN102573915B/zh not_active Expired - Fee Related
- 2010-04-30 CA CA2759873A patent/CA2759873A1/en not_active Abandoned
- 2010-04-30 EP EP10719754A patent/EP2424570A1/en not_active Withdrawn
- 2010-04-30 NZ NZ596058A patent/NZ596058A/xx not_active IP Right Cessation
- 2010-04-30 US US13/318,099 patent/US20120263743A1/en not_active Abandoned
- 2010-04-30 JP JP2012507784A patent/JP2012525134A/ja active Pending
- 2010-04-30 SG SG2011079225A patent/SG175382A1/en unknown
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005517632A (ja) * | 2001-09-14 | 2005-06-16 | サイトス バイオテクノロジー アーゲー | ウィルス様粒子中への免疫賦活物質のパッケージ化：調製法および使用法 |
| JP2009513532A (ja) * | 2003-07-10 | 2009-04-02 | サイトス バイオテクノロジー アーゲー | パッケージ化ウイルス様粒子 |
| JP2009502789A (ja) * | 2005-07-19 | 2009-01-29 | ダウ グローバル テクノロジーズ インコーポレイティド | 組み換えインフルエンザワクチン |
| US20070042001A1 (en) * | 2005-08-16 | 2007-02-22 | Hawaii Biotech, Inc. | Influenza recombinant subunit vaccine |
| WO2007068747A1 (en) * | 2005-12-14 | 2007-06-21 | Cytos Biotechnology Ag | Immunostimulatory nucleic acid packaged particles for the treatment of hypersensitivity |
| US20070253982A1 (en) * | 2006-03-07 | 2007-11-01 | Langzhou Song | Compositions that include hemagglutinin, methods of making and methods of use thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2010125202A1 (en) | 2010-11-04 |
| US20120263743A1 (en) | 2012-10-18 |
| EP2424570A1 (en) | 2012-03-07 |
| NZ596058A (en) | 2013-08-30 |
| AU2010243490A1 (en) | 2011-11-24 |
| CN102573915B (zh) | 2015-02-18 |
| SG175382A1 (en) | 2011-12-29 |
| CA2759873A1 (en) | 2010-11-04 |
| CN102573915A (zh) | 2012-07-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20220305131A1 (en) | Modified virus-like particles of cmv | |
| Mohsen et al. | Virus-like particle vaccinology, from bench to bedside | |
| JP7250878B2 (ja) | 新規多価ナノ粒子に基づくワクチン | |
| RU2540871C2 (ru) | Самоорганизующиеся пептидные наночастицы, полезные в качестве вакцин | |
| AU2004220549B2 (en) | Influenza virus vaccine | |
| RU2468034C2 (ru) | Иммуногенные композиции и способы | |
| AU2006224529B2 (en) | Cat allergen fusion proteins and uses thereof | |
| JP2010535026A (ja) | 多量体マルチエピトープインフルエンザワクチン | |
| CN114213548B (zh) | 同时诱导抗多种病毒的免疫应答的方法 | |
| Park et al. | Chemical and biological conjugation strategies for the development of multivalent protein vaccine nanoparticles | |
| Sun et al. | Toward innovative veterinary nanoparticle vaccines | |
| CN101959526A (zh) | 白介素-1偶联物在糖尿病治疗中的用途 | |
| JP2012525134A (ja) | インフルエンザ赤血球凝集素の組成物とその使用 | |
| ZA200506241B (en) | Influenze virus vaccine | |
| WO2010122164A1 (en) | VIRUS-LIKE PARTICLES OF BACTERIOPHAGE φCB5 | |
| HK40077650A (en) | Modified virus-like particles of cmv | |
| WO2025073874A1 (en) | Vaccine composition comprising m2e nanoparticles and ha1 protein | |
| JP2025536956A (ja) | 目的遺伝子ｒｎａ製剤 | |
| HK1255670B (zh) | Cmv的修饰病毒样颗粒 | |
| BR122024008858B1 (pt) | Uso de uma composição farmacêutica compreendendo uma partícula semelhante a vírus (vlp) modificada do vírus do mosaico do pepino (cmv) e um antígeno no tratamento de uma doença, distúrbio ou condição em um animal ou ser humano |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130418 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20130418 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20140826 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20141125 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20141202 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20150526 |