TW201335178A - 包含重組毒素之抗難養芽胞梭菌疫苗 - Google Patents
包含重組毒素之抗難養芽胞梭菌疫苗 Download PDFInfo
- Publication number
- TW201335178A TW201335178A TW102103026A TW102103026A TW201335178A TW 201335178 A TW201335178 A TW 201335178A TW 102103026 A TW102103026 A TW 102103026A TW 102103026 A TW102103026 A TW 102103026A TW 201335178 A TW201335178 A TW 201335178A
- Authority
- TW
- Taiwan
- Prior art keywords
- protein
- seq
- tcda
- tcdb
- cdta
- Prior art date
Links
- 108700012359 toxins Proteins 0.000 title claims abstract description 154
- 231100000765 toxin Toxicity 0.000 title claims abstract description 136
- 239000003053 toxin Substances 0.000 title claims abstract description 129
- 241000193163 Clostridioides difficile Species 0.000 title claims abstract description 22
- 229960005486 vaccine Drugs 0.000 title abstract description 69
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 262
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 248
- 230000035772 mutation Effects 0.000 claims abstract description 148
- 239000000203 mixture Substances 0.000 claims abstract description 90
- 230000014509 gene expression Effects 0.000 claims abstract description 57
- 230000002163 immunogen Effects 0.000 claims abstract description 52
- 241000701447 unidentified baculovirus Species 0.000 claims abstract description 48
- 238000000034 method Methods 0.000 claims abstract description 40
- 241000238631 Hexapoda Species 0.000 claims abstract description 32
- 101710084578 Short neurotoxin 1 Proteins 0.000 claims abstract description 23
- 101710182532 Toxin a Proteins 0.000 claims abstract description 23
- 239000002671 adjuvant Substances 0.000 claims description 64
- 239000002773 nucleotide Substances 0.000 claims description 51
- 125000003729 nucleotide group Chemical group 0.000 claims description 51
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 49
- 241000193155 Clostridium botulinum Species 0.000 claims description 47
- 241000193403 Clostridium Species 0.000 claims description 45
- 108010076504 Protein Sorting Signals Proteins 0.000 claims description 40
- 239000013598 vector Substances 0.000 claims description 33
- 102100021324 5-azacytidine-induced protein 2 Human genes 0.000 claims description 30
- 108090001007 Interleukin-8 Proteins 0.000 claims description 30
- 238000004519 manufacturing process Methods 0.000 claims description 17
- 150000007523 nucleic acids Chemical class 0.000 claims description 17
- 102220488184 Olfactory receptor 2A12_Y67A_mutation Human genes 0.000 claims description 16
- 102000039446 nucleic acids Human genes 0.000 claims description 16
- 108020004707 nucleic acids Proteins 0.000 claims description 16
- 238000011282 treatment Methods 0.000 claims description 15
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 14
- 229910052782 aluminium Inorganic materials 0.000 claims description 14
- 201000010099 disease Diseases 0.000 claims description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 14
- 239000003937 drug carrier Substances 0.000 claims description 14
- 208000003508 Botulism Diseases 0.000 claims description 13
- 102220475348 Junctional protein associated with coronary artery disease_R255A_mutation Human genes 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 12
- 230000004913 activation Effects 0.000 claims description 10
- 230000002265 prevention Effects 0.000 claims description 9
- 108010042653 IgA receptor Proteins 0.000 claims description 4
- 102100034014 Prolyl 3-hydroxylase 3 Human genes 0.000 claims description 4
- 108030001720 Bontoxilysin Proteins 0.000 claims description 3
- 229940053031 botulinum toxin Drugs 0.000 claims description 3
- 102220485325 ATP-dependent DNA/RNA helicase DHX36_Y69A_mutation Human genes 0.000 claims 2
- 230000001131 transforming effect Effects 0.000 claims 2
- 230000000694 effects Effects 0.000 abstract description 34
- 208000015181 infectious disease Diseases 0.000 abstract description 26
- 231100000419 toxicity Toxicity 0.000 abstract description 25
- 230000001988 toxicity Effects 0.000 abstract description 25
- 101710182223 Toxin B Proteins 0.000 abstract description 21
- 230000028993 immune response Effects 0.000 abstract description 11
- 238000003259 recombinant expression Methods 0.000 abstract description 6
- 230000001939 inductive effect Effects 0.000 abstract description 5
- 235000018102 proteins Nutrition 0.000 description 185
- 210000004027 cell Anatomy 0.000 description 76
- 125000000539 amino acid group Chemical group 0.000 description 66
- 241000588724 Escherichia coli Species 0.000 description 57
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 48
- 108020004414 DNA Proteins 0.000 description 34
- 235000001014 amino acid Nutrition 0.000 description 31
- 229940024606 amino acid Drugs 0.000 description 27
- 102000004190 Enzymes Human genes 0.000 description 26
- 108090000790 Enzymes Proteins 0.000 description 26
- 229940088598 enzyme Drugs 0.000 description 26
- 241000194107 Bacillus megaterium Species 0.000 description 24
- 238000004458 analytical method Methods 0.000 description 24
- 241000699800 Cricetinae Species 0.000 description 22
- 108090000765 processed proteins & peptides Proteins 0.000 description 21
- 150000001413 amino acids Chemical class 0.000 description 20
- 229920001184 polypeptide Polymers 0.000 description 20
- 102000004196 processed proteins & peptides Human genes 0.000 description 20
- 241001465754 Metazoa Species 0.000 description 18
- 108091028043 Nucleic acid sequence Proteins 0.000 description 17
- 230000003197 catalytic effect Effects 0.000 description 17
- 239000000427 antigen Substances 0.000 description 16
- 108091007433 antigens Proteins 0.000 description 16
- 102000036639 antigens Human genes 0.000 description 16
- 108020004705 Codon Proteins 0.000 description 13
- 108010021466 Mutant Proteins Proteins 0.000 description 13
- 102000008300 Mutant Proteins Human genes 0.000 description 13
- 238000012217 deletion Methods 0.000 description 13
- 230000037430 deletion Effects 0.000 description 13
- 230000002255 enzymatic effect Effects 0.000 description 13
- 238000006467 substitution reaction Methods 0.000 description 13
- 230000027455 binding Effects 0.000 description 12
- 239000012634 fragment Substances 0.000 description 12
- 102220582522 Actin, cytoplasmic 1_Y69A_mutation Human genes 0.000 description 11
- 208000037384 Clostridium Infections Diseases 0.000 description 11
- 238000000746 purification Methods 0.000 description 11
- 238000007792 addition Methods 0.000 description 10
- 230000004075 alteration Effects 0.000 description 10
- 230000008901 benefit Effects 0.000 description 10
- 239000013604 expression vector Substances 0.000 description 10
- 230000036039 immunity Effects 0.000 description 10
- 238000002649 immunization Methods 0.000 description 10
- 230000003053 immunization Effects 0.000 description 10
- 230000002779 inactivation Effects 0.000 description 10
- 230000001965 increasing effect Effects 0.000 description 10
- 239000003795 chemical substances by application Substances 0.000 description 9
- 230000004048 modification Effects 0.000 description 9
- 238000012986 modification Methods 0.000 description 9
- 102000007469 Actins Human genes 0.000 description 8
- 108010085238 Actins Proteins 0.000 description 8
- 239000003550 marker Substances 0.000 description 8
- 230000003472 neutralizing effect Effects 0.000 description 8
- 230000001681 protective effect Effects 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 238000003556 assay Methods 0.000 description 7
- 235000018417 cysteine Nutrition 0.000 description 7
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 7
- 230000005847 immunogenicity Effects 0.000 description 7
- 230000006698 induction Effects 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 238000012552 review Methods 0.000 description 7
- 102100040678 Programmed cell death protein 1 Human genes 0.000 description 6
- 102220603752 SLAM family member 5_Y62A_mutation Human genes 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 229940047712 aluminum hydroxyphosphate Drugs 0.000 description 6
- 239000000539 dimer Substances 0.000 description 6
- 239000008194 pharmaceutical composition Substances 0.000 description 6
- 102000040430 polynucleotide Human genes 0.000 description 6
- 108091033319 polynucleotide Proteins 0.000 description 6
- 239000002157 polynucleotide Substances 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 238000002255 vaccination Methods 0.000 description 6
- 108010049290 ADP Ribose Transferases Proteins 0.000 description 5
- 102000009062 ADP Ribose Transferases Human genes 0.000 description 5
- 101100356682 Caenorhabditis elegans rho-1 gene Proteins 0.000 description 5
- 241000282693 Cercopithecidae Species 0.000 description 5
- 238000002965 ELISA Methods 0.000 description 5
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 5
- 101150111584 RHOA gene Proteins 0.000 description 5
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 5
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 5
- 125000003118 aryl group Chemical group 0.000 description 5
- 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 5
- 239000013078 crystal Substances 0.000 description 5
- 210000000805 cytoplasm Anatomy 0.000 description 5
- 238000011156 evaluation Methods 0.000 description 5
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 239000000178 monomer Substances 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 239000013605 shuttle vector Substances 0.000 description 5
- 239000000758 substrate Substances 0.000 description 5
- 239000006228 supernatant Substances 0.000 description 5
- 230000004083 survival effect Effects 0.000 description 5
- 230000005945 translocation Effects 0.000 description 5
- 210000003501 vero cell Anatomy 0.000 description 5
- 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 4
- 206010009657 Clostridium difficile colitis Diseases 0.000 description 4
- 241000193468 Clostridium perfringens Species 0.000 description 4
- 108091026890 Coding region Proteins 0.000 description 4
- 102000005927 Cysteine Proteases Human genes 0.000 description 4
- 108010005843 Cysteine Proteases Proteins 0.000 description 4
- 108091034117 Oligonucleotide Proteins 0.000 description 4
- 101710089372 Programmed cell death protein 1 Proteins 0.000 description 4
- 208000003100 Pseudomembranous Enterocolitis Diseases 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 230000002411 adverse Effects 0.000 description 4
- 239000003242 anti bacterial agent Substances 0.000 description 4
- 230000006907 apoptotic process Effects 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 4
- 238000004113 cell culture Methods 0.000 description 4
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- 229960002227 clindamycin Drugs 0.000 description 4
- 231100000135 cytotoxicity Toxicity 0.000 description 4
- 230000003013 cytotoxicity Effects 0.000 description 4
- 238000006731 degradation reaction Methods 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 238000004255 ion exchange chromatography Methods 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000001262 western blot Methods 0.000 description 4
- 241000193830 Bacillus <bacterium> Species 0.000 description 3
- 241000252852 Campylobacter faecalis Species 0.000 description 3
- 208000034628 Celiac artery compression syndrome Diseases 0.000 description 3
- 206010012735 Diarrhoea Diseases 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 235000004279 alanine Nutrition 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 230000003115 biocidal effect Effects 0.000 description 3
- 210000004899 c-terminal region Anatomy 0.000 description 3
- 101150108363 cdtB gene Proteins 0.000 description 3
- 238000012512 characterization method Methods 0.000 description 3
- 238000007385 chemical modification Methods 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 231100001102 clostridial toxin Toxicity 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 238000006471 dimerization reaction Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 108020001507 fusion proteins Proteins 0.000 description 3
- 102000037865 fusion proteins Human genes 0.000 description 3
- 238000011553 hamster model Methods 0.000 description 3
- 238000003306 harvesting Methods 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 229930182817 methionine Natural products 0.000 description 3
- 238000000569 multi-angle light scattering Methods 0.000 description 3
- 231100000350 mutagenesis Toxicity 0.000 description 3
- 238000006384 oligomerization reaction Methods 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 230000010287 polarization Effects 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000011321 prophylaxis Methods 0.000 description 3
- 230000006798 recombination Effects 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- 230000009261 transgenic effect Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 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 2
- 230000005730 ADP ribosylation Effects 0.000 description 2
- 241000190888 Capnocytophaga gingivalis Species 0.000 description 2
- 101800001318 Capsid protein VP4 Proteins 0.000 description 2
- 229930186147 Cephalosporin Natural products 0.000 description 2
- 108010021408 Clostridium perfringens iota toxin Proteins 0.000 description 2
- 208000035473 Communicable disease Diseases 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 238000012286 ELISA Assay Methods 0.000 description 2
- 101710146739 Enterotoxin Proteins 0.000 description 2
- 102000051366 Glycosyltransferases Human genes 0.000 description 2
- 108700023372 Glycosyltransferases Proteins 0.000 description 2
- 102000002812 Heat-Shock Proteins Human genes 0.000 description 2
- 108010004889 Heat-Shock Proteins Proteins 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- 241000282553 Macaca Species 0.000 description 2
- 241000699673 Mesocricetus auratus Species 0.000 description 2
- KPKZJLCSROULON-QKGLWVMZSA-N Phalloidin Chemical compound N1C(=O)[C@@H]([C@@H](O)C)NC(=O)[C@H](C)NC(=O)[C@H](C[C@@](C)(O)CO)NC(=O)[C@H](C2)NC(=O)[C@H](C)NC(=O)[C@@H]3C[C@H](O)CN3C(=O)[C@@H]1CSC1=C2C2=CC=CC=C2N1 KPKZJLCSROULON-QKGLWVMZSA-N 0.000 description 2
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
- 206010037128 Pseudomembranous colitis Diseases 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 102100027609 Rho-related GTP-binding protein RhoD Human genes 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 102000004357 Transferases Human genes 0.000 description 2
- 108090000992 Transferases Proteins 0.000 description 2
- 102100022153 Tumor necrosis factor receptor superfamily member 4 Human genes 0.000 description 2
- 108010059993 Vancomycin Proteins 0.000 description 2
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 2
- 239000012615 aggregate Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N aspartic acid group Chemical group N[C@@H](CC(=O)O)C(=O)O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 210000002421 cell wall Anatomy 0.000 description 2
- 229940124587 cephalosporin Drugs 0.000 description 2
- 150000001780 cephalosporins Chemical class 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 229960005091 chloramphenicol Drugs 0.000 description 2
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound 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 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 230000000112 colonic effect Effects 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 150000001945 cysteines Chemical class 0.000 description 2
- 210000004292 cytoskeleton Anatomy 0.000 description 2
- 230000002498 deadly effect Effects 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 239000007857 degradation product Substances 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 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 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 239000000147 enterotoxin Substances 0.000 description 2
- 231100000655 enterotoxin Toxicity 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 229940124307 fluoroquinolone Drugs 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 230000013595 glycosylation Effects 0.000 description 2
- 238000006206 glycosylation reaction Methods 0.000 description 2
- 238000009396 hybridization Methods 0.000 description 2
- 230000003308 immunostimulating effect Effects 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 230000002147 killing effect Effects 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 231100000518 lethal Toxicity 0.000 description 2
- 230000001665 lethal effect Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 description 2
- 229960000282 metronidazole Drugs 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 238000006386 neutralization reaction Methods 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 150000003904 phospholipids Chemical class 0.000 description 2
- 210000002706 plastid Anatomy 0.000 description 2
- 230000006337 proteolytic cleavage Effects 0.000 description 2
- 238000005215 recombination Methods 0.000 description 2
- 108091008146 restriction endonucleases Proteins 0.000 description 2
- 102000007268 rho GTP-Binding Proteins Human genes 0.000 description 2
- 108010033674 rho GTP-Binding Proteins Proteins 0.000 description 2
- 229930182490 saponin Natural products 0.000 description 2
- 150000007949 saponins Chemical class 0.000 description 2
- 235000017709 saponins Nutrition 0.000 description 2
- 238000002741 site-directed mutagenesis Methods 0.000 description 2
- 239000012609 strong anion exchange resin Substances 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 238000011285 therapeutic regimen Methods 0.000 description 2
- 230000002463 transducing effect Effects 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 230000014616 translation Effects 0.000 description 2
- 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 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 229960003165 vancomycin Drugs 0.000 description 2
- 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 2
- 230000003612 virological effect Effects 0.000 description 2
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
- AXAVXPMQTGXXJZ-UHFFFAOYSA-N 2-aminoacetic acid;2-amino-2-(hydroxymethyl)propane-1,3-diol Chemical compound NCC(O)=O.OCC(N)(CO)CO AXAVXPMQTGXXJZ-UHFFFAOYSA-N 0.000 description 1
- 208000012968 Acquired central diabetes insipidus Diseases 0.000 description 1
- 229910017119 AlPO Inorganic materials 0.000 description 1
- KHOITXIGCFIULA-UHFFFAOYSA-N Alophen Chemical compound C1=CC(OC(=O)C)=CC=C1C(C=1N=CC=CC=1)C1=CC=C(OC(C)=O)C=C1 KHOITXIGCFIULA-UHFFFAOYSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 241000194108 Bacillus licheniformis Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 231100000699 Bacterial toxin Toxicity 0.000 description 1
- 239000002028 Biomass Substances 0.000 description 1
- 101150013553 CD40 gene Proteins 0.000 description 1
- 102100025221 CD70 antigen Human genes 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 108010022172 Chitinases Proteins 0.000 description 1
- 102000009016 Cholera Toxin Human genes 0.000 description 1
- 108010049048 Cholera Toxin Proteins 0.000 description 1
- 108090000317 Chymotrypsin Proteins 0.000 description 1
- 241001522796 Clostridioides difficile CD196 Species 0.000 description 1
- 108700022831 Clostridium difficile toxB Proteins 0.000 description 1
- 241000186581 Clostridium novyi Species 0.000 description 1
- 241000193449 Clostridium tetani Species 0.000 description 1
- 108700010070 Codon Usage Proteins 0.000 description 1
- 208000037041 Community-Acquired Infections Diseases 0.000 description 1
- 238000011537 Coomassie blue staining Methods 0.000 description 1
- 241001147547 Croceicoccus mobilis Species 0.000 description 1
- 206010011409 Cross infection Diseases 0.000 description 1
- 239000004971 Cross linker Substances 0.000 description 1
- 108010016626 Dipeptides Proteins 0.000 description 1
- 208000035240 Disease Resistance Diseases 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- -1 Flt- 3L) Proteins 0.000 description 1
- 102000013446 GTP Phosphohydrolases Human genes 0.000 description 1
- 108091006109 GTPases Proteins 0.000 description 1
- 201000000628 Gas Gangrene Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 102000000340 Glucosyltransferases Human genes 0.000 description 1
- 108010055629 Glucosyltransferases Proteins 0.000 description 1
- 101000934356 Homo sapiens CD70 antigen Proteins 0.000 description 1
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 1
- 101000669447 Homo sapiens Toll-like receptor 4 Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010022095 Injection Site reaction Diseases 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- 102000013462 Interleukin-12 Human genes 0.000 description 1
- 108010065805 Interleukin-12 Proteins 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- 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 1
- 239000006142 Luria-Bertani Agar Substances 0.000 description 1
- 238000005004 MAS NMR spectroscopy Methods 0.000 description 1
- 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241000736262 Microbiota Species 0.000 description 1
- 102000002151 Microfilament Proteins Human genes 0.000 description 1
- 108010040897 Microfilament Proteins Proteins 0.000 description 1
- 102000029749 Microtubule Human genes 0.000 description 1
- 108091022875 Microtubule Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
- 125000000729 N-terminal amino-acid group Chemical group 0.000 description 1
- MXRIRQGCELJRSN-UHFFFAOYSA-N O.O.O.[Al] Chemical compound O.O.O.[Al] MXRIRQGCELJRSN-UHFFFAOYSA-N 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241000193465 Paeniclostridium sordellii Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 108010081690 Pertussis Toxin Proteins 0.000 description 1
- 108010009711 Phalloidine Proteins 0.000 description 1
- 241000233622 Phytophthora infestans Species 0.000 description 1
- 102000018120 Recombinases Human genes 0.000 description 1
- 108010091086 Recombinases Proteins 0.000 description 1
- 208000035415 Reinfection Diseases 0.000 description 1
- 241000220010 Rhode Species 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 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 1
- 229930006000 Sucrose Natural products 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 108700005078 Synthetic Genes Proteins 0.000 description 1
- 108010008038 Synthetic Vaccines Proteins 0.000 description 1
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 1
- 238000011053 TCID50 method Methods 0.000 description 1
- 206010043376 Tetanus Diseases 0.000 description 1
- 102000008235 Toll-Like Receptor 9 Human genes 0.000 description 1
- 108010060818 Toll-Like Receptor 9 Proteins 0.000 description 1
- 102000002689 Toll-like receptor Human genes 0.000 description 1
- 108020000411 Toll-like receptor Proteins 0.000 description 1
- 102100039360 Toll-like receptor 4 Human genes 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 101710165473 Tumor necrosis factor receptor superfamily member 4 Proteins 0.000 description 1
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 1
- 108010057266 Type A Botulinum Toxins Proteins 0.000 description 1
- HSCJRCZFDFQWRP-JZMIEXBBSA-N UDP-alpha-D-glucose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OP(O)(=O)OP(O)(=O)OC[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C(NC(=O)C=C2)=O)O1 HSCJRCZFDFQWRP-JZMIEXBBSA-N 0.000 description 1
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical group O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 1
- HSCJRCZFDFQWRP-UHFFFAOYSA-N Uridindiphosphoglukose Natural products OC1C(O)C(O)C(CO)OC1OP(O)(=O)OP(O)(=O)OCC1C(O)C(O)C(N2C(NC(=O)C=C2)=O)O1 HSCJRCZFDFQWRP-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 238000005377 adsorption chromatography Methods 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 229940037003 alum Drugs 0.000 description 1
- 238000012870 ammonium sulfate precipitation Methods 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000001147 anti-toxic effect Effects 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 230000009925 apoptotic mechanism Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-L aspartate group Chemical group N[C@@H](CC(=O)[O-])C(=O)[O-] CKLJMWTZIZZHCS-REOHCLBHSA-L 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 239000000688 bacterial toxin Substances 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 230000004071 biological effect Effects 0.000 description 1
- BBWBEZAMXFGUGK-UHFFFAOYSA-N bis(dodecylsulfanyl)-methylarsane Chemical compound CCCCCCCCCCCCS[As](C)SCCCCCCCCCCCC BBWBEZAMXFGUGK-UHFFFAOYSA-N 0.000 description 1
- OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 1
- 229920001400 block copolymer Polymers 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 235000011132 calcium sulphate Nutrition 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 230000021523 carboxylation Effects 0.000 description 1
- 238000006473 carboxylation reaction Methods 0.000 description 1
- 108020001778 catalytic domains Proteins 0.000 description 1
- 238000012656 cationic ring opening polymerization Methods 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229960002376 chymotrypsin Drugs 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229940063193 cleocin Drugs 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 238000011461 current therapy Methods 0.000 description 1
- 230000000120 cytopathologic effect Effects 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 239000002619 cytotoxin Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 208000028659 discharge Diseases 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000011143 downstream manufacturing Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000002121 endocytic effect Effects 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 210000001163 endosome Anatomy 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- XUFQPHANEAPEMJ-UHFFFAOYSA-N famotidine Chemical compound NC(N)=NC1=NC(CSCCC(N)=NS(N)(=O)=O)=CS1 XUFQPHANEAPEMJ-UHFFFAOYSA-N 0.000 description 1
- 230000002550 fecal effect Effects 0.000 description 1
- 210000003754 fetus Anatomy 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 235000015220 hamburgers Nutrition 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 230000000155 isotopic effect Effects 0.000 description 1
- 229940090046 jet injector Drugs 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- GZQKNULLWNGMCW-PWQABINMSA-N lipid A (E. coli) Chemical compound O1[C@H](CO)[C@@H](OP(O)(O)=O)[C@H](OC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCCCC)[C@@H](NC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCC)[C@@H]1OC[C@@H]1[C@@H](O)[C@H](OC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](NC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](OP(O)(O)=O)O1 GZQKNULLWNGMCW-PWQABINMSA-N 0.000 description 1
- 229920006008 lipopolysaccharide Polymers 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 210000004688 microtubule Anatomy 0.000 description 1
- 229940035032 monophosphoryl lipid a Drugs 0.000 description 1
- 230000001459 mortal effect Effects 0.000 description 1
- 238000002887 multiple sequence alignment Methods 0.000 description 1
- 230000000869 mutational effect Effects 0.000 description 1
- OHDXDNUPVVYWOV-UHFFFAOYSA-N n-methyl-1-(2-naphthalen-1-ylsulfanylphenyl)methanamine Chemical compound CNCC1=CC=CC=C1SC1=CC=CC2=CC=CC=C12 OHDXDNUPVVYWOV-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 244000039328 opportunistic pathogen Species 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 239000005416 organic matter Substances 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229920002627 poly(phosphazenes) Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229940068965 polysorbates Drugs 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 229940021993 prophylactic vaccine Drugs 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 239000003227 purinergic agonist Substances 0.000 description 1
- 239000002510 pyrogen Substances 0.000 description 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
- 125000004151 quinonyl group Chemical group 0.000 description 1
- 239000011535 reaction buffer Substances 0.000 description 1
- 229940124551 recombinant vaccine Drugs 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 239000012723 sample buffer Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L sodium sulphate Substances [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000002187 spin decoupling employing ultra-broadband-inversion sequences generated via simulated annealing Methods 0.000 description 1
- 230000028070 sporulation Effects 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008227 sterile water for injection Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229940021747 therapeutic vaccine Drugs 0.000 description 1
- 238000006177 thiolation reaction Methods 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 238000000954 titration curve Methods 0.000 description 1
- 201000002516 toxic megacolon Diseases 0.000 description 1
- 231100000041 toxicology testing Toxicity 0.000 description 1
- 230000007888 toxin activity Effects 0.000 description 1
- 229940031572 toxoid vaccine Drugs 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- 231100000402 unacceptable toxicity Toxicity 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 239000012646 vaccine adjuvant Substances 0.000 description 1
- 229940124931 vaccine adjuvant Drugs 0.000 description 1
- 229940124856 vaccine component Drugs 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
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
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/10—Transferases (2.)
- C12N9/1048—Glycosyltransferases (2.4)
- C12N9/1077—Pentosyltransferases (2.4.2)
-
- 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
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/52—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from bacteria or Archaea
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55505—Inorganic adjuvants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55577—Saponins; Quil A; QS21; ISCOMS
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- General Engineering & Computer Science (AREA)
- Immunology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Biophysics (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261591631P | 2012-01-27 | 2012-01-27 | |
| US201261596419P | 2012-02-08 | 2012-02-08 | |
| US201261703754P | 2012-09-20 | 2012-09-20 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TW201335178A true TW201335178A (zh) | 2013-09-01 |
Family
ID=48873956
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW102103026A TW201335178A (zh) | 2012-01-27 | 2013-01-25 | 包含重組毒素之抗難養芽胞梭菌疫苗 |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US9388394B2 (enExample) |
| EP (1) | EP2807186A4 (enExample) |
| JP (2) | JP2015506948A (enExample) |
| KR (1) | KR20140117433A (enExample) |
| CN (1) | CN104039816B (enExample) |
| AR (1) | AR089797A1 (enExample) |
| AU (1) | AU2013211973B2 (enExample) |
| BR (1) | BR112014018432A8 (enExample) |
| CA (1) | CA2856443A1 (enExample) |
| IN (1) | IN2014CN04187A (enExample) |
| MX (1) | MX351074B (enExample) |
| RU (1) | RU2014134365A (enExample) |
| TW (1) | TW201335178A (enExample) |
| WO (1) | WO2013112867A1 (enExample) |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SI3505531T1 (sl) | 2011-04-22 | 2024-02-29 | Wyeth Llc | Kompozicije, povezane z mutantnim toksinom clostridium difficile in njegovimii metodami |
| MX2014006630A (es) * | 2011-12-08 | 2014-07-09 | Novartis Ag | Vacuna a base toxina clostridium difficile. |
| BR122016023101B1 (pt) | 2012-10-21 | 2022-03-22 | Pfizer Inc | Polipeptídeo, composição imunogênica que o compreende, bem como célula recombinante derivada de clostridium difficile |
| GB201223342D0 (en) * | 2012-12-23 | 2013-02-06 | Glaxosmithkline Biolog Sa | Immunogenic composition |
| US10226523B2 (en) * | 2013-04-22 | 2019-03-12 | The Board Of Regents Of The University Of Oklahoma | Clostridium difficile vaccine and methods of use |
| WO2014197651A1 (en) * | 2013-06-05 | 2014-12-11 | Tufts University | Atoxic recombinant holotoxins of clostridium difficile as immunogens |
| MX2015017257A (es) | 2013-06-14 | 2016-11-11 | Sanofi Pasteur Inc | Composiciones y metodos de inmunizar contra clostridium difficile. |
| EP3160500B1 (en) | 2014-06-25 | 2019-08-21 | GlaxoSmithKline Biologicals S.A. | Clostridium difficile immunogenic composition |
| JP2017212882A (ja) * | 2014-10-10 | 2017-12-07 | 学校法人 名城大学 | アセチルエステラーゼ及びその利用 |
| US10676723B2 (en) | 2015-05-11 | 2020-06-09 | David Gordon Bermudes | Chimeric protein toxins for expression by therapeutic bacteria |
| JP2018521967A (ja) | 2015-05-15 | 2018-08-09 | サノフィ パストゥール インコーポレイテッド | クロストリジウム・ディフィシルに対する免疫方法 |
| TW201718627A (zh) * | 2015-06-11 | 2017-06-01 | 梅茲製藥有限兩合公司 | 重組梭菌神經毒素及其使用與形成方法、包括其之醫藥組合物及對應其之前驅物、編碼前驅物之核酸序列及其獲得方法與前驅物之形成方法、載體與包括核酸序列之重組宿主細胞 |
| RU2743746C2 (ru) | 2016-03-02 | 2021-02-25 | Мерц Фарма Гмбх Энд Ко. Кгаа | Композиция, содержащая ботулинический токсин |
| US11129906B1 (en) | 2016-12-07 | 2021-09-28 | David Gordon Bermudes | Chimeric protein toxins for expression by therapeutic bacteria |
| WO2018111662A1 (en) * | 2016-12-14 | 2018-06-21 | Merck Sharp & Dohme Corp. | Human genetic markers associated with response to treatments that target clostridium difficile toxin b |
| US10668140B2 (en) | 2017-02-24 | 2020-06-02 | University Of South Floirida | Non-toxigenic Clostridium difficile spores for use in oral vaccination |
| SG11201908376UA (en) * | 2017-03-15 | 2019-10-30 | Novavax Inc | Methods and compositions for inducing immune responses against clostridium difficile |
| US10555992B2 (en) | 2017-05-31 | 2020-02-11 | University Of South Florida | Immunogenic proteins against clostridium difficile |
| JP7349366B2 (ja) | 2017-06-09 | 2023-09-22 | ヒプラ シエンティフィック エセ．エレ．ウ． | クロストリジウム類毒素を含むワクチン |
| WO2018233813A1 (en) | 2017-06-20 | 2018-12-27 | Merz Pharma Gmbh & Co. Kgaa | Novel recombinant botulinum toxin with increased duration of effect |
| ES2930237T3 (es) | 2017-07-06 | 2022-12-09 | Merz Pharma Gmbh & Co Kgaa | Neurotoxinas botulínicas recombinantes nuevas con mayor duración de efectos |
| US10933126B2 (en) | 2018-05-03 | 2021-03-02 | The Board Of Regents Of The University Of Oklahoma | Clostridium difficile immunogenic compositions and methods of use |
| US20200123210A1 (en) * | 2018-10-17 | 2020-04-23 | Eternity Biomedical Laboratories, Inc. | Immunogenic preparations and methods against clostridium difficile infection |
| CN110041437B (zh) * | 2019-04-29 | 2020-12-25 | 中国兽医药品监察所 | 一种无毒性破伤风毒素和诺维梭菌α毒素重组融合蛋白 |
| CN110607314B (zh) * | 2019-10-31 | 2022-09-23 | 四川农业大学 | 一种TcdB RBD基因、重组RBD蛋白和应用 |
| CN112442472B (zh) * | 2020-11-30 | 2023-05-26 | 四川大学华西医院 | 抗艰难梭菌的重组乳酸乳球菌、活载体疫苗及其制备方法 |
| CN118613492A (zh) * | 2022-01-30 | 2024-09-06 | 西湖大学 | Tfpi结合多肽及其用途 |
| JP2023134918A (ja) * | 2022-03-15 | 2023-09-28 | 株式会社荏原製作所 | 研磨方法および研磨装置 |
| WO2025029561A2 (en) * | 2023-07-28 | 2025-02-06 | University Of South Florida | Vaccine containing rbd2 of cdtb component from binary toxin cdt of clostridioides difficile |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5919665A (en) * | 1989-10-31 | 1999-07-06 | Ophidian Pharmaceuticals, Inc. | Vaccine for clostridium botulinum neurotoxin |
| AU746859B2 (en) | 1997-06-20 | 2002-05-02 | Imperial College Of Science, Technology And Medicine | Immonogenic fragments of toxin a of clostridium difficile |
| 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 |
| EP1165796A2 (en) | 1999-04-09 | 2002-01-02 | Techlab, Inc. | Recombinant clostridium toxin a protein carrier for polysaccharide conjugate vaccines |
| AU2003299527A1 (en) | 2002-06-17 | 2004-06-07 | Jimmy D. Ballard | Mutant of clostridium difficile toxin b and methods of use |
| CA2549173A1 (en) | 2003-12-08 | 2005-07-07 | Hybridon, Inc. | Modulation of immunostimulatory properties by small oligonucleotide-based compounds |
| SI2857418T1 (en) | 2004-02-06 | 2018-01-31 | University Of Massachusetts | Antibodies against Clostridium difficile toxins and uses thereof |
| US7470674B2 (en) | 2005-11-07 | 2008-12-30 | Idera Pharmaceuticals, Inc. | Immunostimulatory properties of oligonucleotide-based compounds comprising modified immunostimulatory dinucleotides |
| HUE027091T2 (en) * | 2006-03-30 | 2016-08-29 | Zoetis Services Llc | Procedures and preparations for vaccination of poultry |
| ES2656850T3 (es) * | 2009-02-11 | 2018-02-28 | Cedars-Sinai Medical Center | Diagnóstico del síndrome intestinal inflamatorio con base en la toxina de distensión citoletal |
| JP5740714B2 (ja) * | 2009-02-20 | 2015-06-24 | ヘルス プロテクション エージェンシー | クロストリジウム・ディフィシル（Ｃｌｏｓｔｒｉｄｉｕｍｄｉｆｆｉｃｉｌｅ）毒素に対する抗体 |
| JP2013503198A (ja) | 2009-08-27 | 2013-01-31 | シナプティック リサーチ，リミテッド ライアビリティ カンパニー | 人工多能性幹（ｉＰＳ）細胞または組織特異的細胞を誘導するための新規タンパク質送達系 |
| WO2011060431A2 (en) | 2009-11-16 | 2011-05-19 | University Of Maryland Baltimore | Multivalent live vector vaccine against clostridium difficile-associated disease |
| WO2011068953A2 (en) * | 2009-12-02 | 2011-06-09 | 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 |
| CN103957931B (zh) | 2010-09-03 | 2017-10-24 | 瓦尔内瓦奥地利有限责任公司 | 艰难梭状芽胞杆菌毒素a和毒素b蛋白的分离多肽及其用途 |
| US8431361B2 (en) * | 2010-09-17 | 2013-04-30 | Board Of Regents Of The University Of Oklahoma | Bacterial cells, optimized nucleotide sequences and methods for improved expression of recombinant Clostridium difficile toxin B |
| SI3505531T1 (sl) | 2011-04-22 | 2024-02-29 | Wyeth Llc | Kompozicije, povezane z mutantnim toksinom clostridium difficile in njegovimii metodami |
-
2013
- 2013-01-24 AR ARP130100216A patent/AR089797A1/es unknown
- 2013-01-25 AU AU2013211973A patent/AU2013211973B2/en not_active Ceased
- 2013-01-25 KR KR1020147020672A patent/KR20140117433A/ko not_active Withdrawn
- 2013-01-25 MX MX2014009106A patent/MX351074B/es active IP Right Grant
- 2013-01-25 JP JP2014554865A patent/JP2015506948A/ja active Pending
- 2013-01-25 TW TW102103026A patent/TW201335178A/zh unknown
- 2013-01-25 US US14/374,792 patent/US9388394B2/en active Active
- 2013-01-25 CN CN201380005667.4A patent/CN104039816B/zh not_active Expired - Fee Related
- 2013-01-25 IN IN4187CHN2014 patent/IN2014CN04187A/en unknown
- 2013-01-25 EP EP13740509.8A patent/EP2807186A4/en active Pending
- 2013-01-25 RU RU2014134365A patent/RU2014134365A/ru not_active Application Discontinuation
- 2013-01-25 WO PCT/US2013/023189 patent/WO2013112867A1/en not_active Ceased
- 2013-01-25 CA CA2856443A patent/CA2856443A1/en not_active Abandoned
- 2013-01-25 BR BR112014018432A patent/BR112014018432A8/pt not_active IP Right Cessation
-
2017
- 2017-02-15 JP JP2017026031A patent/JP2017141226A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| US9388394B2 (en) | 2016-07-12 |
| JP2015506948A (ja) | 2015-03-05 |
| KR20140117433A (ko) | 2014-10-07 |
| CN104039816A (zh) | 2014-09-10 |
| MX351074B (es) | 2017-09-28 |
| AR089797A1 (es) | 2014-09-17 |
| JP2017141226A (ja) | 2017-08-17 |
| BR112014018432A2 (enExample) | 2017-06-20 |
| CA2856443A1 (en) | 2013-08-01 |
| EP2807186A4 (en) | 2016-01-27 |
| AU2013211973B2 (en) | 2017-10-12 |
| WO2013112867A1 (en) | 2013-08-01 |
| BR112014018432A8 (pt) | 2017-07-11 |
| MX2014009106A (es) | 2014-11-10 |
| US20150044250A1 (en) | 2015-02-12 |
| AU2013211973A1 (en) | 2014-06-12 |
| EP2807186A1 (en) | 2014-12-03 |
| RU2014134365A (ru) | 2016-03-20 |
| IN2014CN04187A (enExample) | 2015-07-17 |
| CN104039816B (zh) | 2018-02-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US9388394B2 (en) | Vaccines against clostridium difficile comprising recombinant toxins | |
| US11357844B2 (en) | Isolated polypeptide of the toxin A and toxin B proteins of C. difficile and uses thereof | |
| KR101667837B1 (ko) | 돌연변이체 클로스트리듐 디피실레 독소에 관련된 조성물 및 그의 방법 | |
| KR102078517B1 (ko) | 돌연변이체 클로스트리디움 디피실레 독소에 관한 조성물 및 방법 | |
| Tian et al. | A novel fusion protein containing the receptor binding domains of C. difficile toxin A and toxin B elicits protective immunity against lethal toxin and spore challenge in preclinical efficacy models | |
| US12331083B2 (en) | Immunogenic compositions to treat and prevent microbial infections | |
| KR20140101835A (ko) | 클로스트리듐 디피실레 톡신-기반 백신 | |
| US20210369831A1 (en) | Clostridium difficile multi-component vaccine | |
| CN110691609B (zh) | 用于诱导针对艰难梭菌的免疫应答的方法和组合物 | |
| CN104560780B (zh) | 产气荚膜梭菌ε毒素减毒突变体及其应用 | |
| CA2986025A1 (en) | Methods for immunization against clostridium difficile | |
| TWI605056B (zh) | 用於治療艱難梭狀芽孢桿菌（Clostridium difficile）相關疾病之組成物及方法 | |
| US20250304627A1 (en) | Immunogenic Compositions to Treat and Prevent Microbial Infections | |
| RU2781057C2 (ru) | Способы и композиции для индукции иммунного ответа против clostridium difficile | |
| RU2781057C9 (ru) | Способы и композиции для индукции иммунного ответа против clostridium difficile | |
| RU2773880C1 (ru) | Композиции, относящиеся к мутантному токсину CLOSTRIDIUM DIFFICILE, и способы их применения |