RU2630671C2 - Композиции и способы, имеющие отношение к мутантному токсину из Clostridium Difficile - Google Patents
Композиции и способы, имеющие отношение к мутантному токсину из Clostridium Difficile Download PDFInfo
- Publication number
- RU2630671C2 RU2630671C2 RU2015112079A RU2015112079A RU2630671C2 RU 2630671 C2 RU2630671 C2 RU 2630671C2 RU 2015112079 A RU2015112079 A RU 2015112079A RU 2015112079 A RU2015112079 A RU 2015112079A RU 2630671 C2 RU2630671 C2 RU 2630671C2
- Authority
- RU
- Russia
- Prior art keywords
- difficile
- seq
- amino acid
- toxin
- acid sequence
- Prior art date
Links
- 241000193163 Clostridioides difficile Species 0.000 title claims abstract description 697
- 108700012359 toxins Proteins 0.000 title claims abstract description 388
- 231100000765 toxin Toxicity 0.000 title claims abstract description 387
- 239000003053 toxin Substances 0.000 title claims abstract description 386
- 239000000203 mixture Substances 0.000 title claims abstract description 212
- 238000000034 method Methods 0.000 title claims abstract description 116
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 211
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 208
- 229920001184 polypeptide Polymers 0.000 claims abstract description 206
- 230000002163 immunogen Effects 0.000 claims abstract description 118
- 230000003472 neutralizing effect Effects 0.000 claims abstract description 77
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 23
- 101710182223 Toxin B Proteins 0.000 claims description 141
- 101710084578 Short neurotoxin 1 Proteins 0.000 claims description 107
- 101710182532 Toxin a Proteins 0.000 claims description 107
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical group CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims description 105
- 235000001014 amino acid Nutrition 0.000 claims description 95
- 150000001413 amino acids Chemical class 0.000 claims description 85
- 102000040430 polynucleotide Human genes 0.000 claims description 55
- 108091033319 polynucleotide Proteins 0.000 claims description 55
- 239000002157 polynucleotide Substances 0.000 claims description 55
- 229940041514 candida albicans extract Drugs 0.000 claims description 49
- 108090000623 proteins and genes Proteins 0.000 claims description 49
- 239000012138 yeast extract Substances 0.000 claims description 49
- 239000008103 glucose Substances 0.000 claims description 32
- 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 31
- 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 claims description 30
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical group ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 claims description 30
- 238000004132 cross linking Methods 0.000 claims description 30
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 27
- CKLJMWTZIZZHCS-REOHCLBHSA-N aspartic acid group Chemical group N[C@@H](CC(=O)O)C(=O)O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 25
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 23
- 238000004519 manufacturing process Methods 0.000 claims description 22
- 241000894006 Bacteria Species 0.000 claims description 21
- OTVAEFIXJLOWRX-NXEZZACHSA-N thiamphenicol Chemical compound CS(=O)(=O)C1=CC=C([C@@H](O)[C@@H](CO)NC(=O)C(Cl)Cl)C=C1 OTVAEFIXJLOWRX-NXEZZACHSA-N 0.000 claims description 21
- 229960003053 thiamphenicol Drugs 0.000 claims description 21
- 150000007523 nucleic acids Chemical group 0.000 claims description 17
- 239000002202 Polyethylene glycol Substances 0.000 claims description 13
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 claims description 13
- 229920001223 polyethylene glycol Polymers 0.000 claims description 13
- 239000004471 Glycine Substances 0.000 claims description 12
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical group NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 claims description 11
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 claims description 8
- 241000193470 Clostridium sporogenes Species 0.000 claims description 7
- 241000193403 Clostridium Species 0.000 claims description 2
- 230000028070 sporulation Effects 0.000 claims 1
- 125000003275 alpha amino acid group Chemical group 0.000 abstract description 334
- 230000000694 effects Effects 0.000 abstract description 31
- 238000012258 culturing Methods 0.000 abstract description 25
- 239000000126 substance Substances 0.000 abstract description 11
- 238000002360 preparation method Methods 0.000 abstract description 5
- 210000004027 cell Anatomy 0.000 description 231
- 239000001963 growth medium Substances 0.000 description 150
- 239000012634 fragment Substances 0.000 description 135
- 238000009739 binding Methods 0.000 description 115
- 230000027455 binding Effects 0.000 description 114
- 230000035772 mutation Effects 0.000 description 105
- 229940024606 amino acid Drugs 0.000 description 80
- 241000124008 Mammalia Species 0.000 description 66
- 230000003013 cytotoxicity Effects 0.000 description 66
- 231100000135 cytotoxicity Toxicity 0.000 description 66
- 208000015181 infectious disease Diseases 0.000 description 54
- 125000000539 amino acid group Chemical group 0.000 description 53
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 52
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical class O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 51
- 102000000340 Glucosyltransferases Human genes 0.000 description 47
- 108010055629 Glucosyltransferases Proteins 0.000 description 47
- 239000002609 medium Substances 0.000 description 47
- 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 46
- 238000010382 chemical cross-linking Methods 0.000 description 43
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 39
- 229910052799 carbon Inorganic materials 0.000 description 39
- 239000003431 cross linking reagent Substances 0.000 description 35
- 102000005927 Cysteine Proteases Human genes 0.000 description 31
- 108010005843 Cysteine Proteases Proteins 0.000 description 31
- 238000006467 substitution reaction Methods 0.000 description 30
- 108010064851 Plant Proteins Proteins 0.000 description 29
- 235000021118 plant-derived protein Nutrition 0.000 description 29
- 235000010469 Glycine max Nutrition 0.000 description 28
- 239000000427 antigen Substances 0.000 description 28
- 108091007433 antigens Proteins 0.000 description 28
- 102000036639 antigens Human genes 0.000 description 28
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical class ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 28
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 27
- 230000004048 modification Effects 0.000 description 27
- 238000012986 modification Methods 0.000 description 27
- 241000588724 Escherichia coli Species 0.000 description 26
- 201000010099 disease Diseases 0.000 description 26
- 239000003531 protein hydrolysate Substances 0.000 description 26
- 238000011282 treatment Methods 0.000 description 26
- 229930182817 methionine Natural products 0.000 description 24
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 22
- 239000002671 adjuvant Substances 0.000 description 22
- 239000003795 chemical substances by application Substances 0.000 description 22
- 230000028993 immune response Effects 0.000 description 22
- 230000001147 anti-toxic effect Effects 0.000 description 21
- 238000000338 in vitro Methods 0.000 description 21
- 208000024891 symptom Diseases 0.000 description 21
- 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 19
- 235000018102 proteins Nutrition 0.000 description 19
- 102000004169 proteins and genes Human genes 0.000 description 19
- 238000006243 chemical reaction Methods 0.000 description 18
- 238000004458 analytical method Methods 0.000 description 16
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 16
- 231100000263 cytotoxicity test Toxicity 0.000 description 16
- ZKHQWZAMYRWXGA-KQYNXXCUSA-J ATP(4-) Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-J 0.000 description 15
- ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 15
- 238000003556 assay Methods 0.000 description 15
- 238000002784 cytotoxicity assay Methods 0.000 description 15
- 238000000855 fermentation Methods 0.000 description 15
- 230000004151 fermentation Effects 0.000 description 15
- 239000013612 plasmid Substances 0.000 description 15
- 230000000120 cytopathologic effect Effects 0.000 description 14
- 150000003141 primary amines Chemical class 0.000 description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 13
- 241000423301 Clostridioides difficile 630 Species 0.000 description 13
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 13
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 13
- 229960002885 histidine Drugs 0.000 description 13
- 241001522791 Clostridioides difficile R20291 Species 0.000 description 12
- 229940046168 CpG oligodeoxynucleotide Drugs 0.000 description 12
- 239000000872 buffer Substances 0.000 description 12
- 230000002779 inactivation Effects 0.000 description 12
- 230000007246 mechanism Effects 0.000 description 12
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 12
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 12
- 229920000053 polysorbate 80 Polymers 0.000 description 12
- 208000011580 syndromic disease Diseases 0.000 description 12
- 206010012735 Diarrhoea Diseases 0.000 description 11
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 11
- -1 glycine methyl alanine Chemical compound 0.000 description 11
- 230000012010 growth Effects 0.000 description 11
- 229940068968 polysorbate 80 Drugs 0.000 description 11
- 238000011218 seed culture Methods 0.000 description 11
- AIUDWMLXCFRVDR-UHFFFAOYSA-N dimethyl 2-(3-ethyl-3-methylpentyl)propanedioate Chemical compound CCC(C)(CC)CCC(C(=O)OC)C(=O)OC AIUDWMLXCFRVDR-UHFFFAOYSA-N 0.000 description 10
- 230000001965 increasing effect Effects 0.000 description 10
- 230000010412 perfusion Effects 0.000 description 10
- 239000008194 pharmaceutical composition Substances 0.000 description 10
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 9
- 241000699800 Cricetinae Species 0.000 description 9
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 9
- 229910019142 PO4 Inorganic materials 0.000 description 9
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 9
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 9
- 210000001072 colon Anatomy 0.000 description 9
- 230000007918 pathogenicity Effects 0.000 description 9
- 239000010452 phosphate Substances 0.000 description 9
- 229920001451 polypropylene glycol Polymers 0.000 description 9
- 229940074410 trehalose Drugs 0.000 description 9
- 102000013446 GTP Phosphohydrolases Human genes 0.000 description 8
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 8
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 8
- 108700026244 Open Reading Frames Proteins 0.000 description 8
- 125000003277 amino group Chemical group 0.000 description 8
- 238000005119 centrifugation Methods 0.000 description 8
- 238000010367 cloning Methods 0.000 description 8
- 239000000284 extract Substances 0.000 description 8
- 230000001404 mediated effect Effects 0.000 description 8
- 229910052757 nitrogen Inorganic materials 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 230000002195 synergetic effect Effects 0.000 description 8
- 230000001225 therapeutic effect Effects 0.000 description 8
- 239000013598 vector Substances 0.000 description 8
- 208000004998 Abdominal Pain Diseases 0.000 description 7
- 108020004414 DNA Proteins 0.000 description 7
- 108091006109 GTPases Proteins 0.000 description 7
- 239000004472 Lysine Substances 0.000 description 7
- 108010076504 Protein Sorting Signals Proteins 0.000 description 7
- 239000007983 Tris buffer Substances 0.000 description 7
- 235000003704 aspartic acid Nutrition 0.000 description 7
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 7
- 230000003197 catalytic effect Effects 0.000 description 7
- 229960005091 chloramphenicol Drugs 0.000 description 7
- 230000021615 conjugation Effects 0.000 description 7
- 238000001990 intravenous administration Methods 0.000 description 7
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 7
- 230000001717 pathogenic effect Effects 0.000 description 7
- 238000012546 transfer Methods 0.000 description 7
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 7
- 241001522796 Clostridioides difficile CD196 Species 0.000 description 6
- 238000002965 ELISA Methods 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 108091034117 Oligonucleotide Proteins 0.000 description 6
- 206010037660 Pyrexia Diseases 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 230000005875 antibody response Effects 0.000 description 6
- 229960000074 biopharmaceutical Drugs 0.000 description 6
- 238000004113 cell culture Methods 0.000 description 6
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 6
- 238000010790 dilution Methods 0.000 description 6
- 239000012895 dilution Substances 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 6
- 235000013922 glutamic acid Nutrition 0.000 description 6
- 239000004220 glutamic acid Substances 0.000 description 6
- 210000004408 hybridoma Anatomy 0.000 description 6
- 230000000877 morphologic effect Effects 0.000 description 6
- 238000002703 mutagenesis Methods 0.000 description 6
- 231100000350 mutagenesis Toxicity 0.000 description 6
- 238000006386 neutralization reaction Methods 0.000 description 6
- 239000008363 phosphate buffer Substances 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 230000004044 response Effects 0.000 description 6
- 238000002741 site-directed mutagenesis Methods 0.000 description 6
- 239000004094 surface-active agent Substances 0.000 description 6
- 101100356682 Caenorhabditis elegans rho-1 gene Proteins 0.000 description 5
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 5
- 206010061218 Inflammation Diseases 0.000 description 5
- 229930195725 Mannitol Natural products 0.000 description 5
- 239000001888 Peptone Substances 0.000 description 5
- 108010080698 Peptones Proteins 0.000 description 5
- 101150111584 RHOA gene Proteins 0.000 description 5
- 102100022122 Ras-related C3 botulinum toxin substrate 1 Human genes 0.000 description 5
- 239000003242 anti bacterial agent Substances 0.000 description 5
- 238000003776 cleavage reaction Methods 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 229960002433 cysteine Drugs 0.000 description 5
- 231100000433 cytotoxic Toxicity 0.000 description 5
- 230000001472 cytotoxic effect Effects 0.000 description 5
- 238000012217 deletion Methods 0.000 description 5
- 230000037430 deletion Effects 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 230000004054 inflammatory process Effects 0.000 description 5
- 206010024378 leukocytosis Diseases 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 238000004020 luminiscence type Methods 0.000 description 5
- 239000000594 mannitol Substances 0.000 description 5
- 235000010355 mannitol Nutrition 0.000 description 5
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 5
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 description 5
- 229960000282 metronidazole Drugs 0.000 description 5
- 239000002773 nucleotide Substances 0.000 description 5
- 125000003729 nucleotide group Chemical group 0.000 description 5
- 244000052769 pathogen Species 0.000 description 5
- 235000019319 peptone Nutrition 0.000 description 5
- 239000002953 phosphate buffered saline Substances 0.000 description 5
- 230000000069 prophylactic effect Effects 0.000 description 5
- 102000016914 ras Proteins Human genes 0.000 description 5
- 108010014186 ras Proteins Proteins 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 230000001988 toxicity Effects 0.000 description 5
- 231100000419 toxicity Toxicity 0.000 description 5
- 238000001262 western blot Methods 0.000 description 5
- DRHZYJAUECRAJM-DWSYSWFDSA-N (2s,3s,4s,5r,6r)-6-[[(3s,4s,4ar,6ar,6bs,8r,8ar,12as,14ar,14br)-8a-[(2s,3r,4s,5r,6r)-3-[(2s,3r,4s,5r,6s)-5-[(2s,3r,4s,5r)-4-[(2s,3r,4r)-3,4-dihydroxy-4-(hydroxymethyl)oxolan-2-yl]oxy-3,5-dihydroxyoxan-2-yl]oxy-3,4-dihydroxy-6-methyloxan-2-yl]oxy-5-[(3s,5s, Chemical compound O([C@H]1[C@H](O)[C@H](O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O1)O)O[C@H]1CC[C@]2(C)[C@H]3CC=C4[C@@H]5CC(C)(C)CC[C@@]5([C@@H](C[C@@]4(C)[C@]3(C)CC[C@H]2[C@@]1(C=O)C)O)C(=O)O[C@@H]1O[C@H](C)[C@@H]([C@@H]([C@H]1O[C@H]1[C@@H]([C@H](O)[C@@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@](O)(CO)CO3)O)[C@H](O)CO2)O)[C@H](C)O1)O)O)OC(=O)C[C@@H](O)C[C@H](OC(=O)C[C@@H](O)C[C@@H]([C@@H](C)CC)O[C@H]1[C@@H]([C@@H](O)[C@H](CO)O1)O)[C@@H](C)CC)C(O)=O)[C@@H]1OC[C@@H](O)[C@H](O)[C@H]1O DRHZYJAUECRAJM-DWSYSWFDSA-N 0.000 description 4
- 239000004475 Arginine Substances 0.000 description 4
- 206010009657 Clostridium difficile colitis Diseases 0.000 description 4
- 108020004705 Codon Proteins 0.000 description 4
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 4
- 241000196324 Embryophyta Species 0.000 description 4
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 229930091371 Fructose Natural products 0.000 description 4
- 239000005715 Fructose Substances 0.000 description 4
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 4
- 206010018092 Generalised oedema Diseases 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 208000003623 Hypoalbuminemia Diseases 0.000 description 4
- 108060003951 Immunoglobulin Proteins 0.000 description 4
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 206010030113 Oedema Diseases 0.000 description 4
- 241000283973 Oryctolagus cuniculus Species 0.000 description 4
- 208000003100 Pseudomembranous Enterocolitis Diseases 0.000 description 4
- 101150058540 RAC1 gene Proteins 0.000 description 4
- 206010040047 Sepsis Diseases 0.000 description 4
- 210000001744 T-lymphocyte Anatomy 0.000 description 4
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 4
- 108010059993 Vancomycin Proteins 0.000 description 4
- 208000024783 anasarca Diseases 0.000 description 4
- 229940088710 antibiotic agent Drugs 0.000 description 4
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 4
- 230000001580 bacterial effect Effects 0.000 description 4
- 230000003115 biocidal effect Effects 0.000 description 4
- 238000001574 biopsy Methods 0.000 description 4
- 150000001718 carbodiimides Chemical class 0.000 description 4
- 230000002759 chromosomal effect Effects 0.000 description 4
- 230000009260 cross reactivity Effects 0.000 description 4
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 4
- 235000018417 cysteine Nutrition 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 230000008030 elimination Effects 0.000 description 4
- 238000003379 elimination reaction Methods 0.000 description 4
- 235000011187 glycerol Nutrition 0.000 description 4
- 150000002332 glycine derivatives Chemical class 0.000 description 4
- 102000018358 immunoglobulin Human genes 0.000 description 4
- 230000003308 immunostimulating effect Effects 0.000 description 4
- 230000001939 inductive effect Effects 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000003780 insertion Methods 0.000 description 4
- 230000037431 insertion Effects 0.000 description 4
- 239000002502 liposome Substances 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 102000039446 nucleic acids Human genes 0.000 description 4
- 108020004707 nucleic acids Proteins 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 4
- 239000001120 potassium sulphate Substances 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 238000012545 processing Methods 0.000 description 4
- 230000035484 reaction time Effects 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 150000007949 saponins Chemical class 0.000 description 4
- 230000007017 scission Effects 0.000 description 4
- 238000012216 screening Methods 0.000 description 4
- 230000035945 sensitivity Effects 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L sodium sulphate Substances [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- MYPYJXKWCTUITO-LYRMYLQWSA-N vancomycin Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)NC)[C@H]1C[C@](C)(N)[C@H](O)[C@H](C)O1 MYPYJXKWCTUITO-LYRMYLQWSA-N 0.000 description 4
- 229960003165 vancomycin Drugs 0.000 description 4
- MYPYJXKWCTUITO-UHFFFAOYSA-N vancomycin Natural products O1C(C(=C2)Cl)=CC=C2C(O)C(C(NC(C2=CC(O)=CC(O)=C2C=2C(O)=CC=C3C=2)C(O)=O)=O)NC(=O)C3NC(=O)C2NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(CC(C)C)NC)C(O)C(C=C3Cl)=CC=C3OC3=CC2=CC1=C3OC1OC(CO)C(O)C(O)C1OC1CC(C)(N)C(O)C(C)O1 MYPYJXKWCTUITO-UHFFFAOYSA-N 0.000 description 4
- AYIRNRDRBQJXIF-NXEZZACHSA-N (-)-Florfenicol Chemical compound CS(=O)(=O)C1=CC=C([C@@H](O)[C@@H](CF)NC(=O)C(Cl)Cl)C=C1 AYIRNRDRBQJXIF-NXEZZACHSA-N 0.000 description 3
- 229920001817 Agar Polymers 0.000 description 3
- LIRCDOVJWUGTMW-ZWNOBZJWSA-N Chloramphenicol succinate Chemical compound OC(=O)CCC(=O)OC[C@@H](NC(=O)C(Cl)Cl)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 LIRCDOVJWUGTMW-ZWNOBZJWSA-N 0.000 description 3
- 208000037384 Clostridium Infections Diseases 0.000 description 3
- 108010082495 Dietary Plant Proteins Proteins 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 208000018522 Gastrointestinal disease Diseases 0.000 description 3
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 3
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 206010037128 Pseudomembranous colitis Diseases 0.000 description 3
- 238000012300 Sequence Analysis Methods 0.000 description 3
- XCCTYIAWTASOJW-XVFCMESISA-N Uridine-5'-Diphosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(=O)NC(=O)C=C1 XCCTYIAWTASOJW-XVFCMESISA-N 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 235000004279 alanine Nutrition 0.000 description 3
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 3
- 230000000468 autoproteolytic effect Effects 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 230000000747 cardiac effect Effects 0.000 description 3
- 230000003833 cell viability Effects 0.000 description 3
- 238000012054 celltiter-glo Methods 0.000 description 3
- 229960004357 chloramphenicol succinate Drugs 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 229920001577 copolymer Polymers 0.000 description 3
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 230000002950 deficient Effects 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 239000008121 dextrose Substances 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 229940088679 drug related substance Drugs 0.000 description 3
- 230000002255 enzymatic effect Effects 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 239000013604 expression vector Substances 0.000 description 3
- 210000002950 fibroblast Anatomy 0.000 description 3
- 229960003760 florfenicol Drugs 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 229960001031 glucose Drugs 0.000 description 3
- 210000005260 human cell Anatomy 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 230000001771 impaired effect Effects 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 238000011081 inoculation Methods 0.000 description 3
- 239000002054 inoculum Substances 0.000 description 3
- 238000007918 intramuscular administration Methods 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- 229940046166 oligodeoxynucleotide Drugs 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 108091008146 restriction endonucleases Proteins 0.000 description 3
- 229930182490 saponin Natural products 0.000 description 3
- 235000017709 saponins Nutrition 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- 101150032575 tcdA gene Proteins 0.000 description 3
- 101150089436 tcdB gene Proteins 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 238000004448 titration Methods 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- 230000005945 translocation Effects 0.000 description 3
- 229960005486 vaccine Drugs 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- 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 2
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 2
- 231100000582 ATP assay Toxicity 0.000 description 2
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
- 229920000936 Agarose Polymers 0.000 description 2
- 108700028369 Alleles Proteins 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- XFTWUNOVBCHBJR-UHFFFAOYSA-N Aspergillomarasmine A Chemical compound OC(=O)C(N)CNC(C(O)=O)CNC(C(O)=O)CC(O)=O XFTWUNOVBCHBJR-UHFFFAOYSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 102000011068 Cdc42 Human genes 0.000 description 2
- 108050001278 Cdc42 Proteins 0.000 description 2
- GNWUOVJNSFPWDD-XMZRARIVSA-M Cefoxitin sodium Chemical compound [Na+].N([C@]1(OC)C(N2C(=C(COC(N)=O)CS[C@@H]21)C([O-])=O)=O)C(=O)CC1=CC=CS1 GNWUOVJNSFPWDD-XMZRARIVSA-M 0.000 description 2
- 108010035563 Chloramphenicol O-acetyltransferase Proteins 0.000 description 2
- 239000004971 Cross linker Substances 0.000 description 2
- DYDCUQKUCUHJBH-UWTATZPHSA-N D-Cycloserine Chemical compound N[C@@H]1CONC1=O DYDCUQKUCUHJBH-UWTATZPHSA-N 0.000 description 2
- DYDCUQKUCUHJBH-UHFFFAOYSA-N D-Cycloserine Natural products NC1CONC1=O DYDCUQKUCUHJBH-UHFFFAOYSA-N 0.000 description 2
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 2
- 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 2
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 2
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 2
- 229940122957 Histamine H2 receptor antagonist Drugs 0.000 description 2
- 101000963974 Hydrophis stokesii Alpha-elapitoxin-Ast2b Proteins 0.000 description 2
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 2
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 2
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 2
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 2
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 2
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 2
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 2
- 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 2
- 108060001084 Luciferase Proteins 0.000 description 2
- 239000005089 Luciferase Substances 0.000 description 2
- 239000006137 Luria-Bertani broth Substances 0.000 description 2
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 2
- 241001529936 Murinae Species 0.000 description 2
- 101000964025 Naja naja Long neurotoxin 3 Proteins 0.000 description 2
- 229920000954 Polyglycolide Polymers 0.000 description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 108091081024 Start codon Proteins 0.000 description 2
- 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 2
- 229930006000 Sucrose Natural products 0.000 description 2
- PDICCECAPKBDBB-UHFFFAOYSA-N Thelephoric acid Chemical compound O1C2=CC(O)=C(O)C=C2C(C2=O)=C1C(=O)C1=C2OC2=C1C=C(O)C(O)=C2 PDICCECAPKBDBB-UHFFFAOYSA-N 0.000 description 2
- 239000008186 active pharmaceutical agent Substances 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 239000004599 antimicrobial Substances 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 229960002682 cefoxitin Drugs 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 239000013043 chemical agent Substances 0.000 description 2
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 2
- 206010009887 colitis Diseases 0.000 description 2
- 238000002648 combination therapy Methods 0.000 description 2
- 230000006957 competitive inhibition Effects 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 230000008602 contraction Effects 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 231100000599 cytotoxic agent Toxicity 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229960003276 erythromycin Drugs 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 235000013312 flour Nutrition 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 238000012239 gene modification Methods 0.000 description 2
- 230000005017 genetic modification Effects 0.000 description 2
- 235000013617 genetically modified food Nutrition 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 239000012510 hollow fiber Substances 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 230000003053 immunization Effects 0.000 description 2
- 238000002649 immunization Methods 0.000 description 2
- 229940072221 immunoglobulins Drugs 0.000 description 2
- 239000003022 immunostimulating agent Substances 0.000 description 2
- 238000000099 in vitro assay Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000015788 innate immune response Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 238000009630 liquid culture Methods 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 229960000485 methotrexate Drugs 0.000 description 2
- 229940126619 mouse monoclonal antibody Drugs 0.000 description 2
- 230000012666 negative regulation of transcription by glucose Effects 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 230000020477 pH reduction Effects 0.000 description 2
- 238000002823 phage display Methods 0.000 description 2
- OJUGVDODNPJEEC-UHFFFAOYSA-N phenylglyoxal Chemical compound O=CC(=O)C1=CC=CC=C1 OJUGVDODNPJEEC-UHFFFAOYSA-N 0.000 description 2
- 229920001983 poloxamer Polymers 0.000 description 2
- 229920000747 poly(lactic acid) Polymers 0.000 description 2
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 2
- 229920000136 polysorbate Polymers 0.000 description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 description 2
- 239000003223 protective agent Substances 0.000 description 2
- 230000017854 proteolysis Effects 0.000 description 2
- 229940126409 proton pump inhibitor Drugs 0.000 description 2
- 239000000612 proton pump inhibitor Substances 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 238000004062 sedimentation Methods 0.000 description 2
- 238000013207 serial dilution Methods 0.000 description 2
- 102000030938 small GTPase Human genes 0.000 description 2
- 108060007624 small GTPase Proteins 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 101150042065 spo0A gene Proteins 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 239000005720 sucrose 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
- 230000004083 survival effect Effects 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 125000003396 thiol group Chemical group [H]S* 0.000 description 2
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- 238000002255 vaccination Methods 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- 230000003313 weakening effect Effects 0.000 description 2
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical class OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- XUBOMFCQGDBHNK-JTQLQIEISA-N (S)-gatifloxacin Chemical compound FC1=CC(C(C(C(O)=O)=CN2C3CC3)=O)=C2C(OC)=C1N1CCN[C@@H](C)C1 XUBOMFCQGDBHNK-JTQLQIEISA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- FKMHSNTVILORFA-UHFFFAOYSA-N 2-[2-(2-dodecoxyethoxy)ethoxy]ethanol Chemical compound CCCCCCCCCCCCOCCOCCOCCO FKMHSNTVILORFA-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- HVCOBJNICQPDBP-UHFFFAOYSA-N 3-[3-[3,5-dihydroxy-6-methyl-4-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyoxan-2-yl]oxydecanoyloxy]decanoic acid;hydrate Chemical class O.OC1C(OC(CC(=O)OC(CCCCCCC)CC(O)=O)CCCCCCC)OC(C)C(O)C1OC1C(O)C(O)C(O)C(C)O1 HVCOBJNICQPDBP-UHFFFAOYSA-N 0.000 description 1
- XZIIFPSPUDAGJM-UHFFFAOYSA-N 6-chloro-2-n,2-n-diethylpyrimidine-2,4-diamine Chemical compound CCN(CC)C1=NC(N)=CC(Cl)=N1 XZIIFPSPUDAGJM-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 1
- 241000272478 Aquila Species 0.000 description 1
- 208000002109 Argyria Diseases 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- QOFRNSMLZCPQKL-KTIIIUPTSA-N CCN(CC)CC.CCCCCCCCCCCCCC(=O)O[C@H](CCCCCCCCCCC)CC(=O)NCCO[C@@H]1O[C@H](CO)[C@@H](OP(O)(O)=O)[C@H](OC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCCCC)[C@H]1NC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCCCC Chemical compound CCN(CC)CC.CCCCCCCCCCCCCC(=O)O[C@H](CCCCCCCCCCC)CC(=O)NCCO[C@@H]1O[C@H](CO)[C@@H](OP(O)(O)=O)[C@H](OC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCCCC)[C@H]1NC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCCCC QOFRNSMLZCPQKL-KTIIIUPTSA-N 0.000 description 1
- 241000589876 Campylobacter Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 101000617114 Centruroides noxius Beta-toxin Cn9 Proteins 0.000 description 1
- 229930186147 Cephalosporin Natural products 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 241000282552 Chlorocebus aethiops Species 0.000 description 1
- 102000009016 Cholera Toxin Human genes 0.000 description 1
- 108010049048 Cholera Toxin Proteins 0.000 description 1
- 241001112696 Clostridia Species 0.000 description 1
- 101100369013 Clostridioides difficile tcdE gene Proteins 0.000 description 1
- 101100005275 Clostridium perfringens catP gene Proteins 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 206010052360 Colorectal adenocarcinoma Diseases 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 1
- 230000004544 DNA amplification Effects 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- 206010052804 Drug tolerance Diseases 0.000 description 1
- 241000194033 Enterococcus Species 0.000 description 1
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 1
- 241000620209 Escherichia coli DH5[alpha] Species 0.000 description 1
- 241001131785 Escherichia coli HB101 Species 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 241000605909 Fusobacterium Species 0.000 description 1
- 108010026288 GTP Phosphohydrolases Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 241000626621 Geobacillus Species 0.000 description 1
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Polymers OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 1
- 108091029499 Group II intron Proteins 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 241000589989 Helicobacter Species 0.000 description 1
- 101000684275 Homo sapiens ADP-ribosylation factor 3 Proteins 0.000 description 1
- 101001130437 Homo sapiens Ras-related protein Rap-2b Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 1
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 1
- 108010079585 Immunoglobulin Subunits Proteins 0.000 description 1
- 102000012745 Immunoglobulin Subunits Human genes 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- SHZGCJCMOBCMKK-JFNONXLTSA-N L-rhamnopyranose Chemical compound C[C@@H]1OC(O)[C@H](O)[C@H](O)[C@H]1O SHZGCJCMOBCMKK-JFNONXLTSA-N 0.000 description 1
- PNNNRSAQSRJVSB-UHFFFAOYSA-N L-rhamnose Natural products CC(O)C(O)C(O)C(O)C=O PNNNRSAQSRJVSB-UHFFFAOYSA-N 0.000 description 1
- 241000186660 Lactobacillus Species 0.000 description 1
- 241000194036 Lactococcus Species 0.000 description 1
- GSDSWSVVBLHKDQ-JTQLQIEISA-N Levofloxacin Chemical compound C([C@@H](N1C2=C(C(C(C(O)=O)=C1)=O)C=C1F)C)OC2=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-JTQLQIEISA-N 0.000 description 1
- 239000006142 Luria-Bertani Agar Substances 0.000 description 1
- 241000282567 Macaca fascicularis Species 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 241000736262 Microbiota Species 0.000 description 1
- 102000016943 Muramidase Human genes 0.000 description 1
- 108010014251 Muramidase Proteins 0.000 description 1
- 208000007101 Muscle Cramp Diseases 0.000 description 1
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
- 125000000729 N-terminal amino-acid group Chemical group 0.000 description 1
- 241000588653 Neisseria Species 0.000 description 1
- 241001072230 Oceanobacillus Species 0.000 description 1
- 102100026459 POU domain, class 3, transcription factor 2 Human genes 0.000 description 1
- 101710133394 POU domain, class 3, transcription factor 2 Proteins 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- 108010020346 Polyglutamic Acid Proteins 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 241000589540 Pseudomonas fluorescens Species 0.000 description 1
- 102100031421 Ras-related protein Rap-2b Human genes 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 239000002262 Schiff base Substances 0.000 description 1
- 150000004753 Schiff bases Chemical class 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- 230000024932 T cell mediated immunity Effects 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- WPMWEFXCIYCJSA-UHFFFAOYSA-N Tetraethylene glycol monododecyl ether Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCO WPMWEFXCIYCJSA-UHFFFAOYSA-N 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- 241000209140 Triticum Species 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 241000202898 Ureaplasma Species 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- RGUZLDGEKZUCSS-POYBYMJQSA-N [(2r)-2-[(1r)-1-(2,4-dioxopyrimidin-1-yl)-2-oxoethoxy]-3-oxopropyl] phosphono hydrogen phosphate Chemical compound OP(O)(=O)OP(O)(=O)OC[C@H](C=O)O[C@H](C=O)N1C=CC(=O)NC1=O RGUZLDGEKZUCSS-POYBYMJQSA-N 0.000 description 1
- ZBNRGEMZNWHCGA-PDKVEDEMSA-N [(2r)-2-[(2r,3r,4s)-3,4-bis[[(z)-octadec-9-enoyl]oxy]oxolan-2-yl]-2-hydroxyethyl] (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@H]1OC(=O)CCCCCCC\C=C/CCCCCCCC ZBNRGEMZNWHCGA-PDKVEDEMSA-N 0.000 description 1
- UZQJVUCHXGYFLQ-AYDHOLPZSA-N [(2s,3r,4s,5r,6r)-4-[(2s,3r,4s,5r,6r)-4-[(2r,3r,4s,5r,6r)-4-[(2s,3r,4s,5r,6r)-3,5-dihydroxy-6-(hydroxymethyl)-4-[(2s,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,5-dihydroxy-6-(hy Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O)O[C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O)O[C@H]1CC[C@]2(C)[C@H]3CC=C4[C@@]([C@@]3(CC[C@H]2[C@@]1(C=O)C)C)(C)CC(O)[C@]1(CCC(CC14)(C)C)C(=O)O[C@H]1[C@@H]([C@@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O[C@H]4[C@@H]([C@@H](O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O)[C@H](O)[C@@H](CO)O4)O)[C@H](O)[C@@H](CO)O3)O)[C@H](O)[C@@H](CO)O2)O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UZQJVUCHXGYFLQ-AYDHOLPZSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000001252 acrylic acid derivatives Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- TTWYZDPBDWHJOR-IDIVVRGQSA-L adenosine triphosphate disodium Chemical compound [Na+].[Na+].C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O TTWYZDPBDWHJOR-IDIVVRGQSA-L 0.000 description 1
- GZCGUPFRVQAUEE-SLPGGIOYSA-N aldehydo-D-glucose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O GZCGUPFRVQAUEE-SLPGGIOYSA-N 0.000 description 1
- 229940037003 alum Drugs 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 description 1
- DIZPMCHEQGEION-UHFFFAOYSA-H aluminium sulfate (anhydrous) Chemical compound [Al+3].[Al+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O DIZPMCHEQGEION-UHFFFAOYSA-H 0.000 description 1
- 229940024545 aluminum hydroxide Drugs 0.000 description 1
- 229940024546 aluminum hydroxide gel Drugs 0.000 description 1
- SMYKVLBUSSNXMV-UHFFFAOYSA-K aluminum;trihydroxide;hydrate Chemical compound O.[OH-].[OH-].[OH-].[Al+3] SMYKVLBUSSNXMV-UHFFFAOYSA-K 0.000 description 1
- 150000001414 amino alcohols Chemical class 0.000 description 1
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 1
- 239000001099 ammonium carbonate Substances 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 238000011203 antimicrobial therapy Methods 0.000 description 1
- PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 210000003651 basophil Anatomy 0.000 description 1
- 208000013404 behavioral symptom Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 239000006161 blood agar Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- RGVBVVVFSXWUIM-UHFFFAOYSA-M bromo(dimethyl)sulfanium;bromide Chemical compound [Br-].C[S+](C)Br RGVBVVVFSXWUIM-UHFFFAOYSA-M 0.000 description 1
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 101150113771 cdu2 gene Proteins 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 239000013553 cell monolayer Substances 0.000 description 1
- 230000036978 cell physiology Effects 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 230000007541 cellular toxicity Effects 0.000 description 1
- 229940124587 cephalosporin Drugs 0.000 description 1
- 150000001780 cephalosporins Chemical class 0.000 description 1
- MYPYJXKWCTUITO-KIIOPKALSA-N chembl3301825 Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)NC)[C@H]1C[C@](C)(N)C(O)[C@H](C)O1 MYPYJXKWCTUITO-KIIOPKALSA-N 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229960003405 ciprofloxacin Drugs 0.000 description 1
- 229960002227 clindamycin Drugs 0.000 description 1
- KDLRVYVGXIQJDK-AWPVFWJPSA-N clindamycin Chemical compound CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@H](C)Cl)[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](SC)O1 KDLRVYVGXIQJDK-AWPVFWJPSA-N 0.000 description 1
- 208000035850 clinical syndrome Diseases 0.000 description 1
- 238000007621 cluster analysis Methods 0.000 description 1
- 238000012875 competitive assay Methods 0.000 description 1
- 230000009137 competitive binding Effects 0.000 description 1
- 239000012468 concentrated sample Substances 0.000 description 1
- 230000001268 conjugating effect Effects 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 229960003077 cycloserine Drugs 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 210000004292 cytoskeleton Anatomy 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 239000002619 cytotoxin Substances 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 208000010643 digestive system disease Diseases 0.000 description 1
- 239000012470 diluted sample Substances 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 210000001840 diploid cell Anatomy 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 125000003438 dodecyl group Chemical group [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])* 0.000 description 1
- 230000008482 dysregulation Effects 0.000 description 1
- 238000005868 electrolysis reaction Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 231100000174 enterotoxicity Toxicity 0.000 description 1
- 210000003979 eosinophil Anatomy 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 230000002550 fecal effect Effects 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 229940124307 fluoroquinolone Drugs 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 108010074605 gamma-Globulins Proteins 0.000 description 1
- 238000011902 gastrointestinal surgery Methods 0.000 description 1
- 208000018685 gastrointestinal system disease Diseases 0.000 description 1
- 229960003923 gatifloxacin Drugs 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 229960002743 glutamine Drugs 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 150000002337 glycosamines Chemical class 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 150000002338 glycosides Chemical class 0.000 description 1
- ZRALSGWEFCBTJO-UHFFFAOYSA-N guanidine group Chemical group NC(=N)N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 229940025294 hemin Drugs 0.000 description 1
- BTIJJDXEELBZFS-QDUVMHSLSA-K hemin Chemical compound CC1=C(CCC(O)=O)C(C=C2C(CCC(O)=O)=C(C)\C(N2[Fe](Cl)N23)=C\4)=N\C1=C/C2=C(C)C(C=C)=C3\C=C/1C(C)=C(C=C)C/4=N\1 BTIJJDXEELBZFS-QDUVMHSLSA-K 0.000 description 1
- 102000056549 human Fv Human genes 0.000 description 1
- 108700005872 human Fv Proteins 0.000 description 1
- 230000028996 humoral immune response Effects 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 229940124452 immunizing agent Drugs 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003978 infusion fluid Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- 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 1
- 229960000318 kanamycin Drugs 0.000 description 1
- 229930027917 kanamycin Natural products 0.000 description 1
- 229930182823 kanamycin A Natural products 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 229940039696 lactobacillus Drugs 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000004816 latex Substances 0.000 description 1
- 229920000126 latex Polymers 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 229960003376 levofloxacin Drugs 0.000 description 1
- 229960003907 linezolid Drugs 0.000 description 1
- TYZROVQLWOKYKF-ZDUSSCGKSA-N linezolid Chemical compound O=C1O[C@@H](CNC(=O)C)CN1C(C=C1F)=CC=C1N1CCOCC1 TYZROVQLWOKYKF-ZDUSSCGKSA-N 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 239000012139 lysis buffer Substances 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
- 229920002521 macromolecule Polymers 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 238000013048 microbiological method Methods 0.000 description 1
- 210000000274 microglia Anatomy 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 229940035032 monophosphoryl lipid a Drugs 0.000 description 1
- 229960003702 moxifloxacin Drugs 0.000 description 1
- FABPRXSRWADJSP-MEDUHNTESA-N moxifloxacin Chemical compound COC1=C(N2C[C@H]3NCCC[C@H]3C2)C(F)=CC(C(C(C(O)=O)=C2)=O)=C1N2C1CC1 FABPRXSRWADJSP-MEDUHNTESA-N 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 239000003471 mutagenic agent Substances 0.000 description 1
- 231100000707 mutagenic chemical Toxicity 0.000 description 1
- 230000003505 mutagenic effect Effects 0.000 description 1
- 210000004898 n-terminal fragment Anatomy 0.000 description 1
- 125000000913 palmityl group Chemical group [H]C([*])([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])C([H])([H])[H] 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 238000003322 phosphorimaging Methods 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 229920002643 polyglutamic acid Polymers 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 229920000056 polyoxyethylene ether Polymers 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229940068977 polysorbate 20 Drugs 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000006041 probiotic Substances 0.000 description 1
- 230000000529 probiotic effect Effects 0.000 description 1
- 235000018291 probiotics Nutrition 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000011536 re-plating Methods 0.000 description 1
- 230000010837 receptor-mediated endocytosis Effects 0.000 description 1
- 102000007268 rho GTP-Binding Proteins Human genes 0.000 description 1
- 108010033674 rho GTP-Binding Proteins Proteins 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 201000009881 secretory diarrhea Diseases 0.000 description 1
- 239000006152 selective media Substances 0.000 description 1
- 239000008299 semisolid dosage form Substances 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 230000037432 silent mutation Effects 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 229940074404 sodium succinate Drugs 0.000 description 1
- ZDQYSKICYIVCPN-UHFFFAOYSA-L sodium succinate (anhydrous) Chemical compound [Na+].[Na+].[O-]C(=O)CCC([O-])=O ZDQYSKICYIVCPN-UHFFFAOYSA-L 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 229940035044 sorbitan monolaurate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 229960000268 spectinomycin Drugs 0.000 description 1
- UNFWWIHTNXNPBV-WXKVUWSESA-N spectinomycin Chemical compound O([C@@H]1[C@@H](NC)[C@@H](O)[C@H]([C@@H]([C@H]1O1)O)NC)[C@]2(O)[C@H]1O[C@H](C)CC2=O UNFWWIHTNXNPBV-WXKVUWSESA-N 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 125000004079 stearyl group Chemical group [H]C([*])([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])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 101150061166 tetR gene Proteins 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 238000011285 therapeutic regimen Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000002723 toxicity assay Methods 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000014621 translational initiation Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- PIEPQKCYPFFYMG-UHFFFAOYSA-N tris acetate Chemical compound CC(O)=O.OCC(N)(CO)CO PIEPQKCYPFFYMG-UHFFFAOYSA-N 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
- 150000008130 triterpenoid saponins Chemical class 0.000 description 1
- 239000012137 tryptone Substances 0.000 description 1
- 125000000430 tryptophan group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 241001148471 unidentified anaerobic bacterium Species 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 210000003501 vero cell Anatomy 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 230000001018 virulence Effects 0.000 description 1
- 239000000304 virulence factor Substances 0.000 description 1
- 230000007923 virulence factor Effects 0.000 description 1
- 101150038987 xylR gene Proteins 0.000 description 1
Images
Classifications
-
- 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
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/10—Transferases (2.)
- C12N9/1048—Glycosyltransferases (2.4)
- C12N9/1051—Hexosyltransferases (2.4.1)
-
- 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
- A61K39/02—Bacterial antigens
- A61K39/08—Clostridium, e.g. Clostridium tetani
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/33—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Clostridium (G)
-
- 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
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
- C12N1/205—Bacterial isolates
-
- 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
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/38—Chemical stimulation of growth or activity by addition of chemical compounds which are not essential growth factors; Stimulation of growth by removal of a chemical compound
-
- 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
- C12N2330/00—Production
- C12N2330/50—Biochemical production, i.e. in a transformed host cell
-
- 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
- C12N2510/00—Genetically modified cells
- C12N2510/02—Cells for production
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
- C12R2001/00—Microorganisms ; Processes using microorganisms
- C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
- C12R2001/145—Clostridium
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Biomedical Technology (AREA)
- General Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Virology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Gastroenterology & Hepatology (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Mycology (AREA)
- Immunology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261716605P | 2012-10-21 | 2012-10-21 | |
| US61/716,605 | 2012-10-21 | ||
| PCT/IB2013/059183 WO2014060898A2 (en) | 2012-10-21 | 2013-10-07 | Compositions and methods relating to a mutant clostridium difficile toxin |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2015112079A RU2015112079A (ru) | 2016-12-10 |
| RU2630671C2 true RU2630671C2 (ru) | 2017-09-11 |
Family
ID=49546596
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2015112079A RU2630671C2 (ru) | 2012-10-21 | 2013-10-07 | Композиции и способы, имеющие отношение к мутантному токсину из Clostridium Difficile |
Country Status (19)
| Country | Link |
|---|---|
| US (5) | US10787652B2 (enExample) |
| EP (2) | EP3912990A1 (enExample) |
| JP (4) | JP6527661B2 (enExample) |
| KR (5) | KR101940939B1 (enExample) |
| CN (2) | CN104797706B (enExample) |
| AU (5) | AU2013333532C1 (enExample) |
| BR (2) | BR122016023101B1 (enExample) |
| CA (2) | CA2887891C (enExample) |
| DK (1) | DK2909307T3 (enExample) |
| ES (1) | ES2878551T3 (enExample) |
| HR (1) | HRP20211170T1 (enExample) |
| HU (1) | HUE055594T2 (enExample) |
| IL (3) | IL237792B (enExample) |
| MX (2) | MX369289B (enExample) |
| PL (1) | PL2909307T3 (enExample) |
| PT (1) | PT2909307T (enExample) |
| RU (1) | RU2630671C2 (enExample) |
| SI (1) | SI2909307T1 (enExample) |
| WO (1) | WO2014060898A2 (enExample) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2012245904B2 (en) | 2011-04-22 | 2016-04-21 | Wyeth Llc | Compositions relating to a mutant Clostridium difficile toxin and methods thereof |
| BR122016023101B1 (pt) | 2012-10-21 | 2022-03-22 | Pfizer Inc | Polipeptídeo, composição imunogênica que o compreende, bem como célula recombinante derivada de clostridium difficile |
| WO2014144292A2 (en) | 2013-03-15 | 2014-09-18 | Sanofi Pasteur Biologics , Llc | Antibodies against clostridium difficile toxins and methods of using the same |
| WO2016131157A1 (en) * | 2015-02-19 | 2016-08-25 | Immune Biosolutions Inc | Clostridium difficile toxins a and/or b antigen and epitope antibody, and pharmaceutical uses thereof |
| KR101723167B1 (ko) * | 2015-04-28 | 2017-04-05 | 주식회사 대웅 | 보툴리눔 독소의 제조를 위한 배지 조성물 |
| KR101729251B1 (ko) * | 2015-04-28 | 2017-04-21 | 주식회사 대웅 | 보툴리눔 독소의 제조를 위한 배지 조성물 |
| WO2017040885A1 (en) * | 2015-09-03 | 2017-03-09 | The Board Of Regents Of The University Of Oklahoma | Peptide inhibitors of clostridium difficile tcdb toxin |
| EP3558363A1 (en) | 2016-12-21 | 2019-10-30 | Amgen Inc. | Anti-tnf alpha antibody formulations |
| CN106801077A (zh) * | 2017-02-13 | 2017-06-06 | 江南大学 | 一种高效杀灭滴虫等医学原虫的细菌培养上清液的制备方法和及其利用 |
| IL320444A (en) * | 2017-09-28 | 2025-06-01 | Pfizer | Compositions and methods for stimulating an immune response against Clostridium difficile |
| WO2020201985A1 (en) | 2019-04-01 | 2020-10-08 | Pfizer Inc. | Compositions and methods for eliciting an immune response against clostridium difficile |
| MX2021014097A (es) * | 2019-05-21 | 2022-03-11 | Univ California | Composiciones de vacunas para clostridium difficile. |
| EP4146200A4 (en) * | 2020-05-06 | 2024-05-15 | Albert Einstein College of Medicine | AGENTS FOR PREVENTING TISSUE DAMAGE RELATED TO CLOSTRIDIUM DIFFICILE INFECTIONS BY INHIBITING THE BACTERIAL TOXINS TCDA AND TCDB DAMAGED THE INTESTIN |
| WO2021255690A2 (en) | 2020-06-19 | 2021-12-23 | Pfizer Inc. | Immunogenic compositions against clostridioides (clostridium) difficile and methods thereof |
| CA3254452A1 (en) | 2022-03-14 | 2023-09-21 | Pfizer Inc. | ADJUVANT PRODUCTION PROCESSES |
| CN120475988A (zh) | 2022-12-13 | 2025-08-12 | 辉瑞公司 | 免疫原性组合物及引发针对艰难梭菌的免疫应答的方法 |
| WO2025057058A1 (en) | 2023-09-13 | 2025-03-20 | Pfizer Inc. | Methods for producing an adjuvant |
| WO2025257712A1 (en) | 2024-06-12 | 2025-12-18 | Pfizer Inc. | Immunogenic compositions and methods for eliciting an immune response against clostridioides (clostridium) difficile |
Family Cites Families (109)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS58216123A (ja) | 1982-06-10 | 1983-12-15 | Kazue Ueno | 抗血清 |
| US4530833A (en) * | 1982-09-13 | 1985-07-23 | Wilkins Tracy D | Toxins and antibodies of C. difficile |
| US4689299A (en) | 1982-09-30 | 1987-08-25 | University Of Rochester | Human monoclonal antibodies against bacterial toxins |
| EP0154064A1 (en) * | 1984-03-02 | 1985-09-11 | Tracy Dale Wilkins | Toxins and antibodies of C. difficile |
| US4713240A (en) | 1985-04-04 | 1987-12-15 | Research Corporation | Vaccines based on insoluble supports |
| US5358868A (en) | 1987-11-24 | 1994-10-25 | Connaught Laboratories Limited | Genetic detoxification of pertussis toxin |
| US4912094B1 (en) | 1988-06-29 | 1994-02-15 | Ribi Immunochem Research Inc. | Modified lipopolysaccharides and process of preparation |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| US5919665A (en) | 1989-10-31 | 1999-07-06 | Ophidian Pharmaceuticals, Inc. | Vaccine for clostridium botulinum neurotoxin |
| US5601823A (en) | 1989-10-31 | 1997-02-11 | Ophidian Pharmaceuticals, Inc. | Avian antitoxins to clostridium difficle toxin A |
| US5599539A (en) | 1989-10-31 | 1997-02-04 | Ophidian Pharmaceuticals, Inc. | Therapy for clostridial botulinum toxin |
| US5578308A (en) | 1990-02-12 | 1996-11-26 | Capiau; Carine | Glutaraldehyde and formalin detoxified bordetella toxin vaccine |
| US5231003A (en) | 1990-05-11 | 1993-07-27 | Cambridge Bioscience Corporation | Monoclonal antibodies specific for toxin b of clostridium difficile |
| JPH06509866A (ja) | 1991-04-22 | 1994-11-02 | マサチューセッツ ヘルス リサーチ インスティチュート,インコーポレーテッド | 呼吸系ウイルスに対する有効な抗体力価用の血漿試料をスクリーニングする方法 |
| US6221363B1 (en) | 1991-07-11 | 2001-04-24 | Baxter Aktiengesellschaft | Vaccine for the prevention of lyme disease |
| JP4129544B2 (ja) | 1993-03-29 | 2008-08-06 | ファイザー・インク | サポニンアジュバント使用の多成分系クロストリジウム・ワクチン |
| NZ291659A (en) | 1994-09-06 | 2001-04-27 | Galagen Inc | Use in the manufacture of a medicament of an antibody having specific activity against Clostridium difficile, and pharmaceutical compositions comprising Anti-Clostridium difficile bovine immunoglobulin concentrate; for treating diseases associated with Clostridium difficile |
| BR9509903A (pt) | 1994-10-24 | 1997-11-25 | Ophidian Pharm Inc | Proteína de fusão proteína de fus o solúvel composição de matéria célula hospedeira processo para gerar uma antiotoxina neutralizante dirigida contra toxina tipo a de clostridium botulinum anticorpo processo para purificar uma proteina de fusão recombinante derivada de uma toxina tipo a de clostridium botulinum processo para gerar uma antitoxina neutralizante dirigida contra toxina tipo b de clostridium difficile anticorpo processo de tratemento processo para gerar uma antitoxina neutralizante dirigida contra toxina tipo a de clostridium difficile composição processo para vacinar um individuo para produzir antitoxina neutralizante dirigida contra toxina de clostridium difficile processo a detecção de antigenos de clostridium difficile em uma amosta processo de purificação de toxinas de clostridium difficile de uma cultura e processo de generação de uma forma dosagem sólida de uma antitoxina de ave dirigida contra uma proteina de toxina clostridial |
| US6743430B1 (en) | 1995-03-29 | 2004-06-01 | Richard E. Parizek | Multicomponent vaccine containing clostridial and non-clostridial organisms in a low dose |
| US5610023A (en) | 1995-03-31 | 1997-03-11 | Lee Laboratories, Inc. | Method of purification of clostridium difficile toxin A and production of mono-specific antibodies |
| US5919463A (en) | 1995-07-07 | 1999-07-06 | Oravax, Inc. | Clostridium difficle toxins as mucosal adjuvants |
| DE69610106D1 (de) | 1995-07-07 | 2000-10-05 | Oravax Inc | Toxine und toxoide von clostridium difficile als schleimhautadjuvans |
| JPH11510793A (ja) | 1995-07-07 | 1999-09-21 | オラバックス インク. | 胃腸病に対する鼻腔内ワクチン接種 |
| CA2232001C (en) | 1995-09-15 | 2002-12-10 | Dale N. Gerding | Methods and compositions for prevention and treatment of clostridium difficile-associated diseases |
| ATE272409T1 (de) | 1996-09-30 | 2004-08-15 | Univ Arkansas | Verfahren zur erzeugung aktiver immunität durch vakzinkonjugate |
| US20100267012A1 (en) | 1997-11-04 | 2010-10-21 | Bergeron Michel G | Highly conserved genes and their use to generate probes and primers for detection of microorganisms |
| EP2172216A3 (en) | 1997-03-10 | 2010-11-24 | Ottawa Hospital Research Institute | Use of nucleic acids containing unmethylated CpG dinucleotide as an adjuvant |
| US6299881B1 (en) | 1997-03-24 | 2001-10-09 | Henry M. Jackson Foundation For The Advancement Of Military Medicine | Uronium salts for activating hydroxyls, carboxyls, and polysaccharides, and conjugate vaccines, immunogens, and other useful immunological reagents produced using uronium salts |
| US20050106157A1 (en) | 1997-05-27 | 2005-05-19 | Deckers Harm M. | Immunogenic formulations comprising oil bodies |
| EP1000155A1 (en) | 1997-06-20 | 2000-05-17 | QUEEN MARY & WESTFIELD COLLEGE | Immunogenic fragments of toxin a of clostridium difficile |
| DE19739685A1 (de) | 1997-09-10 | 1999-03-11 | Eichel Streiber Christoph Von | Monoklonale Antikörper zur Therapie und Prophylaxe von Erkrankungen durch Clostridium difficile |
| EP1568378B1 (en) | 1997-10-20 | 2016-03-16 | Sanofi Pasteur Biologics, LLC | Immunization against Clostridium difficile disease |
| US6214341B1 (en) | 1997-10-20 | 2001-04-10 | Oravax | Passive immunization against Clostridium difficile disease |
| US6969520B2 (en) | 1997-10-20 | 2005-11-29 | Acambis Inc. | Active immunization against clostridium difficile disease |
| US6733760B1 (en) | 1999-04-09 | 2004-05-11 | Techlab, Inc. | Recombinant toxin A/toxin B vaccine against Clostridium difficile |
| EP1169456B1 (en) | 1999-04-09 | 2012-07-11 | Intercell USA, Inc. | Recombinant production of Clostridium difficile Toxin A or Toxin B |
| JP2002541808A (ja) * | 1999-04-09 | 2002-12-10 | テクラブ, インコーポレイテッド | ポリサッカリド結合体ワクチンのための組換えトキシンaタンパク質キャリア |
| TR200103018T2 (tr) | 1999-04-19 | 2002-02-21 | Beecham Biologicals S.A. Smithkline | İmmünostimülatör oligonükleotid ve saponin içeren katkı bileşikleri. |
| GB0008682D0 (en) | 2000-04-07 | 2000-05-31 | Microbiological Res Authority | Transformation of clostridium difficile |
| PL365453A1 (en) | 2000-05-04 | 2005-01-10 | President And Fellows Of Harvard College | Compounds and methods for the treatment and prevention of bacterial infection |
| DE60217107T2 (de) | 2001-06-20 | 2007-08-23 | Ramot At Tel Aviv University Ltd. | Mehrantigenisches peptid enthaltend mehrere kopien eines epitopes von einem ablagerungsformenden polypeptid und dessen verwendung |
| US20040029129A1 (en) | 2001-10-25 | 2004-02-12 | Liangsu Wang | Identification of essential genes in microorganisms |
| WO2003104453A1 (ja) | 2002-06-05 | 2003-12-18 | 中外製薬株式会社 | 抗体作製方法 |
| WO2004041857A2 (en) | 2002-06-17 | 2004-05-21 | Ballard Jimmy D | Mutant of clostridium difficile toxin b and methods of use |
| US20040235139A1 (en) * | 2002-12-23 | 2004-11-25 | Demain Arnold L. | Clostridium difficile culture and toxin production methods |
| US20050020506A1 (en) | 2003-07-25 | 2005-01-27 | Drapeau Susan J. | Crosslinked compositions comprising collagen and demineralized bone matrix, methods of making and methods of use |
| PL1709170T3 (pl) | 2004-01-16 | 2018-06-29 | Pfenex Inc. | Ekspresja białek ssaczych w Pseudomonas fluorescens |
| NZ530709A (en) * | 2004-01-21 | 2006-07-28 | Agres Ltd | Improved IGA production method |
| JP4588763B2 (ja) | 2004-02-06 | 2010-12-01 | ユニバーシティー オブ マサチューセッツ | クロストリジウム・ディフィシル(Clostridiumdifficile)毒素に対する抗体およびその使用 |
| WO2006071877A2 (en) | 2004-12-27 | 2006-07-06 | Progenics Pharmaceuticals (Nevada), Inc. | Orally deliverable and anti-toxin antibodies and methods for making and using them |
| MXPA06009853A (es) * | 2005-03-03 | 2007-03-29 | Allergan Inc | Medios para bacteria de clostridium y procesos para obtener una toxina clostridial. |
| WO2006130925A1 (en) | 2005-06-10 | 2006-12-14 | Monash University | Genetic manipulation of clostridium difficile |
| GB0512751D0 (en) * | 2005-06-22 | 2005-07-27 | Glaxo Group Ltd | New adjuvant |
| WO2007090126A2 (en) | 2006-01-30 | 2007-08-09 | Invitrogen Corporation | Compositions and methods for detecting and quantifying toxic substances in disease states |
| GB0612301D0 (en) | 2006-06-21 | 2006-08-02 | Morvus Technology Ltd | DNA molecules and methods |
| US20080206819A1 (en) | 2006-08-21 | 2008-08-28 | Mary Tsao | Intensified Perfusion Production Method |
| EP2813144A1 (en) * | 2006-10-09 | 2014-12-17 | Charleston Laboratories, Inc. | Analgesic compositions comprising an antihistamine |
| US9023352B2 (en) | 2007-02-20 | 2015-05-05 | Tufts University | Methods, compositions and kits for treating a subject using a recombinant heteromultimeric neutralizing binding protein |
| EP2014760A1 (en) | 2007-06-13 | 2009-01-14 | CMC Biopharmaceuticals A/S | A method for producing a biopolymer (e.g. polypeptide) in a continuous fermentation process |
| US9096638B2 (en) | 2007-09-06 | 2015-08-04 | Geneohm Sciences Canada, Inc. | Detection of toxigenic strains of Clostridium difficile |
| CN101855336B (zh) | 2007-09-14 | 2019-07-30 | 赛诺菲巴斯德生物制剂有限责任公司 | 含艰难梭菌类毒素a和b的药物组合物 |
| WO2009132082A2 (en) | 2008-04-22 | 2009-10-29 | Medical College Of Georgia Research Institute, Inc. | Immunogenic compositions containing ceramide and methods of use thereof |
| US8206940B2 (en) | 2008-05-15 | 2012-06-26 | Tufts University | Methods for diagnosis of Clostridium difficile and methods and vectors for recombinant toxin expression |
| WO2009156852A1 (en) | 2008-06-25 | 2009-12-30 | Novartis Ag | Rapid responses to delayed booster immunisations |
| EP2146490A1 (en) | 2008-07-18 | 2010-01-20 | Alcatel, Lucent | User device for gesture based exchange of information, methods for gesture based exchange of information between a plurality of user devices, and related devices and systems |
| US20120020996A1 (en) * | 2008-08-06 | 2012-01-26 | Jonathan Lewis Telfer | Vaccines against clostridium difficile and methods of use |
| US9115347B2 (en) * | 2008-09-24 | 2015-08-25 | Sanofi Pasteur Biologies, LLC | Methods and compositions for increasing toxin production |
| US8444996B2 (en) * | 2008-10-01 | 2013-05-21 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Multicomponent vaccine for malaria providing long-lasting immune responses against plasmodia |
| WO2010037402A1 (en) | 2008-10-02 | 2010-04-08 | Dako Denmark A/S | Molecular vaccines for infectious disease |
| SG171934A1 (en) | 2008-12-03 | 2011-07-28 | Boehringer Ingelheim Vetmed | Process for production of vaccines |
| EP2376107B1 (en) | 2008-12-09 | 2014-05-21 | Coley Pharmaceutical Group, Inc. | Immunostimulatory oligonucleotides |
| GB0901001D0 (en) | 2009-01-22 | 2009-03-04 | Univ Nottingham | Methods |
| EP2405940B1 (en) | 2009-02-20 | 2021-08-04 | Secretary of State for Health and Social Care | Antibodies to clostridium difficile toxins |
| EP2470664A4 (en) | 2009-08-27 | 2013-01-16 | Synaptic Res Llc | NEW PROTEIN RELEASE SYSTEM FOR GENERATING INDUCED PLURIPOTENTAL STEM CELLS OR TISSUE-SPECIFIC CELLS |
| WO2011060431A2 (en) | 2009-11-16 | 2011-05-19 | University Of Maryland Baltimore | Multivalent live vector vaccine against clostridium difficile-associated disease |
| AU2010325992A1 (en) | 2009-12-02 | 2012-05-31 | Tufts University | Atoxic recombinant holotoxins of Clostridium difficile as immunogens |
| GB0921288D0 (en) | 2009-12-04 | 2010-01-20 | Health Prot Agency | Therapies for preventing or suppressing clostridium difficile infection |
| TW201136603A (en) | 2010-02-09 | 2011-11-01 | Merck Sharp & Amp Dohme Corp | 15-valent pneumococcal polysaccharide-protein conjugate vaccine composition |
| US8530171B2 (en) * | 2010-03-30 | 2013-09-10 | Pfenex Inc. | High level expression of recombinant toxin proteins |
| US8765399B2 (en) * | 2010-05-18 | 2014-07-01 | Montefiore Medical Center | Cultures and protocols for diagnosis of toxigenic Clostridium difficile |
| WO2012028418A1 (en) * | 2010-09-02 | 2012-03-08 | Novacem Limited | Integrated process for producing compositions containing magnesium |
| JP6121421B2 (ja) * | 2010-09-03 | 2017-04-26 | バルネバ オーストリア ジーエムビーエイチ | C.ディフィシルの毒素aおよび毒素bタンパク質の単離ポリペプチドならびにその使用 |
| GB201016742D0 (en) * | 2010-10-05 | 2010-11-17 | Health Prot Agency | Clostridium difficile antigens |
| WO2012078313A2 (en) | 2010-11-12 | 2012-06-14 | Reflexion Pharmaceuticals, Inc. | Gb1 peptidic libraries and compounds, and methods of screening the same |
| CN102533867A (zh) * | 2010-12-10 | 2012-07-04 | 西北民族大学 | 一种艰难梭菌a毒素的类毒素的制备方法 |
| AU2012245904B2 (en) | 2011-04-22 | 2016-04-21 | Wyeth Llc | Compositions relating to a mutant Clostridium difficile toxin and methods thereof |
| US9290565B2 (en) * | 2011-05-27 | 2016-03-22 | Glaxosmithkline Biologicals, S.A. | Immunogenic composition |
| WO2012166991A1 (en) | 2011-05-31 | 2012-12-06 | The Board Of Regents Of The University Of Texas Systeem | S-nitrosylation of glucosylating toxins and uses therefor |
| WO2013082298A2 (en) * | 2011-11-30 | 2013-06-06 | Board Of Trustees Of Michigan State University | Immunological composition for clostridium difficile |
| CN103974718A (zh) * | 2011-12-08 | 2014-08-06 | 诺华股份有限公司 | 基于艰难梭菌毒素的疫苗 |
| AR089797A1 (es) | 2012-01-27 | 2014-09-17 | Merck Sharp & Dohme | Vacunas contra clostridum difficile que comprenden toxinas recombinantes |
| MX2015002485A (es) * | 2012-09-19 | 2015-06-05 | Novartis Ag | Polipeptidos de clostridium difficile como vacuna. |
| BR122016023101B1 (pt) * | 2012-10-21 | 2022-03-22 | Pfizer Inc | Polipeptídeo, composição imunogênica que o compreende, bem como célula recombinante derivada de clostridium difficile |
| US10117933B2 (en) * | 2012-11-28 | 2018-11-06 | Emergent Biosolutions Canada Inc. | Antibodies against Clostridium difficile |
| LT2928489T (lt) * | 2012-12-05 | 2019-04-10 | Glaxosmithkline Biologicals S.A. | Imunogeninė kompozicija |
| GB201223342D0 (en) * | 2012-12-23 | 2013-02-06 | Glaxosmithkline Biolog Sa | Immunogenic composition |
| WO2014144292A2 (en) * | 2013-03-15 | 2014-09-18 | Sanofi Pasteur Biologics , Llc | Antibodies against clostridium difficile toxins and methods of using the same |
| JP2016516721A (ja) * | 2013-03-15 | 2016-06-09 | サノフィ パストゥール インコーポレイテッド | トキソイド、組成物および関連方法 |
| US20170165375A1 (en) | 2013-04-02 | 2017-06-15 | Stc. Unm | Antibiotic protocells and related pharmaceutical formulations and methods of treatment |
| SG11201510166YA (en) | 2013-06-14 | 2016-01-28 | Sanofi Pasteur Inc | Compositions and methods of immunizing against c. difficile |
| EP3060246A4 (en) * | 2013-10-23 | 2017-08-16 | The Rockefeller University | Compositions and methods for prophylaxis and therapy of clostridium difficile infection |
| US11160855B2 (en) | 2014-01-21 | 2021-11-02 | Pfizer Inc. | Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof |
| US10947494B2 (en) | 2015-11-17 | 2021-03-16 | Pfizer Inc. | Media and fermentation methods for producing polysaccharides in bacterial cell culture |
| US10813988B2 (en) * | 2016-02-16 | 2020-10-27 | President And Fellows Of Harvard College | Pathogen vaccines and methods of producing and using the same |
| IL269258B2 (en) | 2017-03-15 | 2023-09-01 | Novavax Inc | Methods and compositions for inducing immune responses against Clostridium difficile |
| CA3016351A1 (en) | 2017-09-05 | 2019-03-05 | Mcmaster University | Aptamers for clostridium difficile detection |
| IL320444A (en) | 2017-09-28 | 2025-06-01 | Pfizer | Compositions and methods for stimulating an immune response against Clostridium difficile |
| WO2020201985A1 (en) | 2019-04-01 | 2020-10-08 | Pfizer Inc. | Compositions and methods for eliciting an immune response against clostridium difficile |
| WO2021255690A2 (en) | 2020-06-19 | 2021-12-23 | Pfizer Inc. | Immunogenic compositions against clostridioides (clostridium) difficile and methods thereof |
-
2013
- 2013-10-01 BR BR122016023101-1A patent/BR122016023101B1/pt active IP Right Grant
- 2013-10-07 HU HUE13786535A patent/HUE055594T2/hu unknown
- 2013-10-07 KR KR1020177017169A patent/KR101940939B1/ko active Active
- 2013-10-07 CA CA2887891A patent/CA2887891C/en active Active
- 2013-10-07 SI SI201331900T patent/SI2909307T1/sl unknown
- 2013-10-07 ES ES13786535T patent/ES2878551T3/es active Active
- 2013-10-07 CN CN201380054635.3A patent/CN104797706B/zh active Active
- 2013-10-07 PT PT137865358T patent/PT2909307T/pt unknown
- 2013-10-07 HR HRP20211170TT patent/HRP20211170T1/hr unknown
- 2013-10-07 AU AU2013333532A patent/AU2013333532C1/en active Active
- 2013-10-07 CA CA3063892A patent/CA3063892C/en active Active
- 2013-10-07 WO PCT/IB2013/059183 patent/WO2014060898A2/en not_active Ceased
- 2013-10-07 EP EP21171606.3A patent/EP3912990A1/en active Pending
- 2013-10-07 KR KR1020197001177A patent/KR101990272B1/ko active Active
- 2013-10-07 KR KR1020157009888A patent/KR101751822B1/ko active Active
- 2013-10-07 MX MX2015004986A patent/MX369289B/es active IP Right Grant
- 2013-10-07 MX MX2019013075A patent/MX379863B/es unknown
- 2013-10-07 US US14/436,875 patent/US10787652B2/en active Active
- 2013-10-07 BR BR112015008844-9A patent/BR112015008844B1/pt active IP Right Grant
- 2013-10-07 CN CN201810000818.1A patent/CN108004286B/zh active Active
- 2013-10-07 EP EP13786535.8A patent/EP2909307B1/en active Active
- 2013-10-07 KR KR1020197016516A patent/KR102078517B1/ko active Active
- 2013-10-07 RU RU2015112079A patent/RU2630671C2/ru active
- 2013-10-07 KR KR1020207003847A patent/KR102169216B1/ko active Active
- 2013-10-07 DK DK13786535.8T patent/DK2909307T3/da active
- 2013-10-07 PL PL13786535.8T patent/PL2909307T3/pl unknown
- 2013-10-17 JP JP2013216224A patent/JP6527661B2/ja active Active
-
2015
- 2015-03-16 IL IL237792A patent/IL237792B/en active IP Right Grant
-
2017
- 2017-02-22 AU AU2017201193A patent/AU2017201193C1/en active Active
-
2018
- 2018-08-19 US US16/104,938 patent/US10982198B2/en active Active
-
2019
- 2019-05-06 AU AU2019203159A patent/AU2019203159B2/en active Active
- 2019-05-13 JP JP2019090728A patent/JP6871969B2/ja active Active
- 2019-12-01 IL IL271064A patent/IL271064B/en unknown
- 2019-12-05 US US16/704,744 patent/US11208633B2/en active Active
-
2020
- 2020-05-25 AU AU2020203423A patent/AU2020203423A1/en not_active Abandoned
- 2020-07-07 US US16/922,952 patent/US11952597B2/en active Active
-
2021
- 2021-04-16 JP JP2021069760A patent/JP7208293B2/ja active Active
- 2021-07-04 IL IL284582A patent/IL284582B2/en unknown
- 2021-11-29 AU AU2021277590A patent/AU2021277590A1/en not_active Abandoned
-
2023
- 2023-01-05 JP JP2023000594A patent/JP7556987B2/ja active Active
-
2024
- 2024-03-01 US US18/593,348 patent/US20250002875A1/en active Pending
Non-Patent Citations (1)
| Title |
|---|
| FANG A. et al. Production of Clostridium difficile toxin in a medium totally free of both animal and dairy proteins or digests, Proceedings of the National Academy of Sciences, 2009. MICHAELS J.D. et al. Polyvinyl alcohol and polyethylene glycol as protectants against fluid-mechanical injury of freely-suspended animal cells (CRL 8018), Journal of Biotechnology, 1991. HEAP J.T. et al. A modular system for Clostridium shuttle plasmids, Journal of Microbiological Methods, 2009. MOCRIEF J.S. et al. Genetic characterization of toxin A-negative, toxin B-positive Clostridium difficile isolates by PCR, Journal of Clinical Microbiology, 2000. HEAP J.T. et al. The ClosTron: Mutagenesis in Clostridium refined and streamlined, Journal of Microbiological Methods, 2010. ВАРФОЛОМЕЕВА Н.А. и др. Генно-инженерный подход к получению фрагментов токсина А и В для диагностики и иммунотерапии Clostridium difficile инфекции. Молекулярная генетика, микробиология и вирусология, 2003. * |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7556987B2 (ja) | 突然変異クロストリジウム・ディフィシル(Clostridium difficile)毒素に関する組成物および方法 | |
| CN107022532B (zh) | 涉及突变体难辨梭菌毒素的组合物及其方法 | |
| HK40035897A (en) | Compositions relating to a mutant clostridium difficile toxin and methods thereof | |
| HK1254448B (en) | Compositions and methods relating to a mutant clostridium difficile toxin | |
| HK1242375A1 (en) | Compositions relating to a mutant clostridium difficile toxin and methods thereof | |
| HK1212385B (zh) | 涉及突变型艰难梭菌毒素的组合物和方法 | |
| HK1195325B (en) | Compositions relating to a mutant clostridium difficile toxin and methods thereof |