KR101773368B1 - 단백질 A(SpA) 변이체와 관련된 조성물 및 방법 - Google Patents
단백질 A(SpA) 변이체와 관련된 조성물 및 방법 Download PDFInfo
- Publication number
- KR101773368B1 KR101773368B1 KR1020117026053A KR20117026053A KR101773368B1 KR 101773368 B1 KR101773368 B1 KR 101773368B1 KR 1020117026053 A KR1020117026053 A KR 1020117026053A KR 20117026053 A KR20117026053 A KR 20117026053A KR 101773368 B1 KR101773368 B1 KR 101773368B1
- Authority
- KR
- South Korea
- Prior art keywords
- delete delete
- protein
- spa
- staphylococcus
- domain
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 184
- 238000000034 method Methods 0.000 title claims abstract description 76
- 108090000623 proteins and genes Proteins 0.000 title abstract description 421
- 102000004169 proteins and genes Human genes 0.000 title abstract description 398
- 241000191940 Staphylococcus Species 0.000 claims abstract description 253
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 328
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 285
- 229920001184 polypeptide Polymers 0.000 claims description 211
- 208000015181 infectious disease Diseases 0.000 claims description 134
- 230000027455 binding Effects 0.000 claims description 114
- 239000000427 antigen Substances 0.000 claims description 106
- 108091007433 antigens Proteins 0.000 claims description 106
- 102000036639 antigens Human genes 0.000 claims description 106
- 238000009739 binding Methods 0.000 claims description 104
- 239000012634 fragment Substances 0.000 claims description 93
- 230000028993 immune response Effects 0.000 claims description 89
- 150000007523 nucleic acids Chemical class 0.000 claims description 85
- 229960005486 vaccine Drugs 0.000 claims description 85
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 71
- 235000001014 amino acid Nutrition 0.000 claims description 71
- 230000002163 immunogen Effects 0.000 claims description 62
- 238000006467 substitution reaction Methods 0.000 claims description 58
- 102000039446 nucleic acids Human genes 0.000 claims description 55
- 108020004707 nucleic acids Proteins 0.000 claims description 55
- 150000001413 amino acids Chemical group 0.000 claims description 52
- 238000011282 treatment Methods 0.000 claims description 28
- 238000004519 manufacturing process Methods 0.000 claims description 16
- 230000001939 inductive effect Effects 0.000 claims description 15
- 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 claims description 14
- 108700035708 EsaB Proteins 0.000 claims description 12
- 230000002265 prevention Effects 0.000 claims description 12
- 230000000890 antigenic effect Effects 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 9
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 9
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 6
- 239000004472 Lysine Substances 0.000 claims description 6
- 230000004936 stimulating effect Effects 0.000 claims description 6
- 235000004279 alanine Nutrition 0.000 claims description 4
- 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 4
- 125000003295 alanine group Chemical class N[C@@H](C)C(=O)* 0.000 claims description 3
- 230000000638 stimulation Effects 0.000 claims description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 2
- 231100000252 nontoxic Toxicity 0.000 claims description 2
- 230000003000 nontoxic effect Effects 0.000 claims description 2
- 101000582398 Staphylococcus aureus Replication initiation protein Proteins 0.000 claims 7
- 230000001551 toxigenic effect Effects 0.000 abstract description 20
- 231100000033 toxigenic Toxicity 0.000 abstract description 18
- 208000035143 Bacterial infection Diseases 0.000 abstract description 6
- 208000022362 bacterial infectious disease Diseases 0.000 abstract description 6
- 235000018102 proteins Nutrition 0.000 description 390
- 206010000269 abscess Diseases 0.000 description 66
- 210000004027 cell Anatomy 0.000 description 66
- 241001465754 Metazoa Species 0.000 description 51
- 229940027941 immunoglobulin g Drugs 0.000 description 51
- 108060003951 Immunoglobulin Proteins 0.000 description 50
- 102000018358 immunoglobulin Human genes 0.000 description 50
- 241000699670 Mus sp. Species 0.000 description 48
- 206010057190 Respiratory tract infections Diseases 0.000 description 46
- 229940024606 amino acid Drugs 0.000 description 45
- 239000002671 adjuvant Substances 0.000 description 42
- 230000003053 immunization Effects 0.000 description 41
- 230000001580 bacterial effect Effects 0.000 description 38
- 150000004676 glycans Chemical class 0.000 description 38
- 238000002649 immunization Methods 0.000 description 37
- 210000003719 b-lymphocyte Anatomy 0.000 description 36
- 229920001282 polysaccharide Polymers 0.000 description 36
- 239000005017 polysaccharide Substances 0.000 description 36
- 230000014509 gene expression Effects 0.000 description 35
- 239000013598 vector Substances 0.000 description 34
- 241000894006 Bacteria Species 0.000 description 33
- 102000018697 Membrane Proteins Human genes 0.000 description 33
- 108010052285 Membrane Proteins Proteins 0.000 description 33
- 238000012360 testing method Methods 0.000 description 32
- 230000003993 interaction Effects 0.000 description 31
- 108010047303 von Willebrand Factor Proteins 0.000 description 31
- 150000002632 lipids Chemical class 0.000 description 29
- 102100036537 von Willebrand factor Human genes 0.000 description 29
- 229960001134 von willebrand factor Drugs 0.000 description 29
- 230000015572 biosynthetic process Effects 0.000 description 27
- 230000000694 effects Effects 0.000 description 26
- 230000003902 lesion Effects 0.000 description 26
- 210000001519 tissue Anatomy 0.000 description 26
- 201000010099 disease Diseases 0.000 description 25
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 25
- 210000005084 renal tissue Anatomy 0.000 description 25
- 102000014914 Carrier Proteins Human genes 0.000 description 24
- 239000000463 material Substances 0.000 description 24
- 241000191967 Staphylococcus aureus Species 0.000 description 23
- 108091028043 Nucleic acid sequence Proteins 0.000 description 22
- 230000006870 function Effects 0.000 description 22
- 241000699666 Mus <mouse, genus> Species 0.000 description 21
- 230000001681 protective effect Effects 0.000 description 21
- 239000000243 solution Substances 0.000 description 21
- 230000036039 immunity Effects 0.000 description 20
- 239000002953 phosphate buffered saline Substances 0.000 description 20
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 19
- 108010078791 Carrier Proteins Proteins 0.000 description 19
- 241000283973 Oryctolagus cuniculus Species 0.000 description 19
- 231100000776 exotoxin Toxicity 0.000 description 19
- 239000002095 exotoxin Substances 0.000 description 19
- 238000009472 formulation Methods 0.000 description 19
- 238000000338 in vitro Methods 0.000 description 19
- 230000035772 mutation Effects 0.000 description 18
- OTLLEIBWKHEHGU-UHFFFAOYSA-N 2-[5-[[5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy]-3,4-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,5-dihydroxy-4-phosphonooxyhexanedioic acid Chemical compound C1=NC=2C(N)=NC=NC=2N1C(C(C1O)O)OC1COC1C(CO)OC(OC(C(O)C(OP(O)(O)=O)C(O)C(O)=O)C(O)=O)C(O)C1O OTLLEIBWKHEHGU-UHFFFAOYSA-N 0.000 description 17
- 150000001875 compounds Chemical class 0.000 description 17
- 108091033319 polynucleotide Proteins 0.000 description 17
- 102000040430 polynucleotide Human genes 0.000 description 17
- 239000002157 polynucleotide Substances 0.000 description 17
- 238000002965 ELISA Methods 0.000 description 16
- 230000001965 increasing effect Effects 0.000 description 15
- 210000003734 kidney Anatomy 0.000 description 15
- 230000004044 response Effects 0.000 description 15
- 230000028327 secretion Effects 0.000 description 15
- 230000002588 toxic effect Effects 0.000 description 15
- 241000295644 Staphylococcaceae Species 0.000 description 14
- 210000001744 T-lymphocyte Anatomy 0.000 description 14
- 238000003556 assay Methods 0.000 description 14
- -1 autolysinamidase Proteins 0.000 description 14
- 210000002421 cell wall Anatomy 0.000 description 14
- 239000000047 product Substances 0.000 description 14
- 239000000758 substrate Substances 0.000 description 14
- 108091008875 B cell receptors Proteins 0.000 description 13
- 108010049003 Fibrinogen Proteins 0.000 description 13
- 102000008946 Fibrinogen Human genes 0.000 description 13
- 101710187743 Tumor necrosis factor receptor superfamily member 1A Proteins 0.000 description 13
- 102100033732 Tumor necrosis factor receptor superfamily member 1A Human genes 0.000 description 13
- 108091008324 binding proteins Proteins 0.000 description 13
- 229940012952 fibrinogen Drugs 0.000 description 13
- 229940039716 prothrombin Drugs 0.000 description 13
- 231100000331 toxic Toxicity 0.000 description 13
- 108010065152 Coagulase Proteins 0.000 description 12
- 210000004369 blood Anatomy 0.000 description 12
- 239000008280 blood Substances 0.000 description 12
- 102000037865 fusion proteins Human genes 0.000 description 12
- 108020001507 fusion proteins Proteins 0.000 description 12
- 238000002347 injection Methods 0.000 description 12
- 239000007924 injection Substances 0.000 description 12
- 206010035664 Pneumonia Diseases 0.000 description 11
- 108010094028 Prothrombin Proteins 0.000 description 11
- 102100027378 Prothrombin Human genes 0.000 description 11
- 208000037854 Staphylococcus abscess Diseases 0.000 description 11
- 210000000224 granular leucocyte Anatomy 0.000 description 11
- 229940072221 immunoglobulins Drugs 0.000 description 11
- 230000037361 pathway Effects 0.000 description 11
- 230000000069 prophylactic effect Effects 0.000 description 11
- 230000001105 regulatory effect Effects 0.000 description 11
- 239000000523 sample Substances 0.000 description 11
- 239000000725 suspension Substances 0.000 description 11
- 102000005416 ATP-Binding Cassette Transporters Human genes 0.000 description 10
- 108010006533 ATP-Binding Cassette Transporters Proteins 0.000 description 10
- 241001529936 Murinae Species 0.000 description 10
- 108010076504 Protein Sorting Signals Proteins 0.000 description 10
- 230000004913 activation Effects 0.000 description 10
- 239000003242 anti bacterial agent Substances 0.000 description 10
- 210000004899 c-terminal region Anatomy 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- 238000011161 development Methods 0.000 description 10
- 230000018109 developmental process Effects 0.000 description 10
- 239000003446 ligand Substances 0.000 description 10
- 210000000056 organ Anatomy 0.000 description 10
- 230000001717 pathogenic effect Effects 0.000 description 10
- 150000003839 salts Chemical group 0.000 description 10
- 239000000126 substance Substances 0.000 description 10
- 230000001225 therapeutic effect Effects 0.000 description 10
- 108010077805 Bacterial Proteins Proteins 0.000 description 9
- 108091026890 Coding region Proteins 0.000 description 9
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- 239000004480 active ingredient Substances 0.000 description 9
- 125000000539 amino acid group Chemical group 0.000 description 9
- 230000007123 defense Effects 0.000 description 9
- 235000004554 glutamine Nutrition 0.000 description 9
- 230000028996 humoral immune response Effects 0.000 description 9
- 244000052769 pathogen Species 0.000 description 9
- 239000013612 plasmid Substances 0.000 description 9
- 238000002255 vaccination Methods 0.000 description 9
- 229920001817 Agar Polymers 0.000 description 8
- 102100026189 Beta-galactosidase Human genes 0.000 description 8
- 102000004127 Cytokines Human genes 0.000 description 8
- 108090000695 Cytokines Proteins 0.000 description 8
- 101710128530 Fibrinogen-binding protein Proteins 0.000 description 8
- 108010000851 Laminin Receptors Proteins 0.000 description 8
- 102000002297 Laminin Receptors Human genes 0.000 description 8
- 102000004882 Lipase Human genes 0.000 description 8
- 108090001060 Lipase Proteins 0.000 description 8
- 239000004367 Lipase Substances 0.000 description 8
- 241000404883 Pisa Species 0.000 description 8
- 102100027287 Serpin H1 Human genes 0.000 description 8
- 108050008290 Serpin H1 Proteins 0.000 description 8
- 238000001042 affinity chromatography Methods 0.000 description 8
- 230000007423 decrease Effects 0.000 description 8
- 108010064033 elastin-binding proteins Proteins 0.000 description 8
- 239000013604 expression vector Substances 0.000 description 8
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 8
- 238000001990 intravenous administration Methods 0.000 description 8
- 235000019421 lipase Nutrition 0.000 description 8
- 239000007788 liquid Substances 0.000 description 8
- 238000011068 loading method Methods 0.000 description 8
- 239000011777 magnesium Substances 0.000 description 8
- 239000002773 nucleotide Substances 0.000 description 8
- 125000003729 nucleotide group Chemical group 0.000 description 8
- 239000008194 pharmaceutical composition Substances 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 210000000952 spleen Anatomy 0.000 description 8
- 230000004083 survival effect Effects 0.000 description 8
- 238000002560 therapeutic procedure Methods 0.000 description 8
- 101710187798 60S ribosomal protein L23 Proteins 0.000 description 7
- 101000822695 Clostridium perfringens (strain 13 / Type A) Small, acid-soluble spore protein C1 Proteins 0.000 description 7
- 102000002268 Hexosaminidases Human genes 0.000 description 7
- 108010000540 Hexosaminidases Proteins 0.000 description 7
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 7
- 101000686985 Mouse mammary tumor virus (strain C3H) Protein PR73 Proteins 0.000 description 7
- 101000576807 Protobothrops flavoviridis Small serum protein 2 Proteins 0.000 description 7
- 108091030066 RNAIII Proteins 0.000 description 7
- 241000700159 Rattus Species 0.000 description 7
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 7
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 7
- 101000815632 Streptococcus suis (strain 05ZYH33) Rqc2 homolog RqcH Proteins 0.000 description 7
- 241000700605 Viruses Species 0.000 description 7
- 239000008272 agar Substances 0.000 description 7
- 238000010171 animal model Methods 0.000 description 7
- 230000008901 benefit Effects 0.000 description 7
- 239000000872 buffer Substances 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 238000003776 cleavage reaction Methods 0.000 description 7
- 238000011260 co-administration Methods 0.000 description 7
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 7
- 239000000839 emulsion Substances 0.000 description 7
- 102000025748 fibrinogen binding proteins Human genes 0.000 description 7
- 102000036072 fibronectin binding proteins Human genes 0.000 description 7
- 238000003018 immunoassay Methods 0.000 description 7
- 238000001727 in vivo Methods 0.000 description 7
- 239000003550 marker Substances 0.000 description 7
- 210000004379 membrane Anatomy 0.000 description 7
- 239000012528 membrane Substances 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 230000007017 scission Effects 0.000 description 7
- 210000002966 serum Anatomy 0.000 description 7
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 231100000617 superantigen Toxicity 0.000 description 7
- 230000001988 toxicity Effects 0.000 description 7
- 231100000419 toxicity Toxicity 0.000 description 7
- 238000013518 transcription Methods 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 101100478373 Bacillus subtilis (strain 168) srtD gene Proteins 0.000 description 6
- 101000822677 Clostridium perfringens (strain 13 / Type A) Small, acid-soluble spore protein 1 Proteins 0.000 description 6
- 108020004705 Codon Proteins 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- 241000588724 Escherichia coli Species 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 108010073385 Fibrin Proteins 0.000 description 6
- 102000009123 Fibrin Human genes 0.000 description 6
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 6
- 241000192125 Firmicutes Species 0.000 description 6
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 description 6
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 6
- CPLXHLVBOLITMK-UHFFFAOYSA-N Magnesium oxide Chemical compound [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 101000576806 Protobothrops flavoviridis Small serum protein 1 Proteins 0.000 description 6
- 125000003277 amino group Chemical group 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- 230000007547 defect Effects 0.000 description 6
- 238000012217 deletion Methods 0.000 description 6
- 230000037430 deletion Effects 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- 229940088598 enzyme Drugs 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 229950003499 fibrin Drugs 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 230000005847 immunogenicity Effects 0.000 description 6
- 244000005700 microbiome Species 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 101150087718 srtA gene Proteins 0.000 description 6
- 230000035897 transcription Effects 0.000 description 6
- QFVHZQCOUORWEI-UHFFFAOYSA-N 4-[(4-anilino-5-sulfonaphthalen-1-yl)diazenyl]-5-hydroxynaphthalene-2,7-disulfonic acid Chemical compound C=12C(O)=CC(S(O)(=O)=O)=CC2=CC(S(O)(=O)=O)=CC=1N=NC(C1=CC=CC(=C11)S(O)(=O)=O)=CC=C1NC1=CC=CC=C1 QFVHZQCOUORWEI-UHFFFAOYSA-N 0.000 description 5
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 5
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 5
- 241000282412 Homo Species 0.000 description 5
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 5
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 5
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 description 5
- MSFSPUZXLOGKHJ-UHFFFAOYSA-N Muraminsaeure Natural products OC(=O)C(C)OC1C(N)C(O)OC(CO)C1O MSFSPUZXLOGKHJ-UHFFFAOYSA-N 0.000 description 5
- 108010013639 Peptidoglycan Proteins 0.000 description 5
- 206010040047 Sepsis Diseases 0.000 description 5
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 5
- 229940088710 antibiotic agent Drugs 0.000 description 5
- CKLJMWTZIZZHCS-REOHCLBHSA-N aspartic acid group Chemical group N[C@@H](CC(=O)O)C(=O)O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 5
- 230000002238 attenuated effect Effects 0.000 description 5
- 230000003115 biocidal effect Effects 0.000 description 5
- 229940098773 bovine serum albumin Drugs 0.000 description 5
- 230000001419 dependent effect Effects 0.000 description 5
- 239000003623 enhancer Substances 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 229940098197 human immunoglobulin g Drugs 0.000 description 5
- 230000006698 induction Effects 0.000 description 5
- 230000000977 initiatory effect Effects 0.000 description 5
- 230000015788 innate immune response Effects 0.000 description 5
- 238000011081 inoculation Methods 0.000 description 5
- 230000000670 limiting effect Effects 0.000 description 5
- 230000001404 mediated effect Effects 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 229960003085 meticillin Drugs 0.000 description 5
- 229920001542 oligosaccharide Polymers 0.000 description 5
- 150000002482 oligosaccharides Chemical class 0.000 description 5
- 239000012188 paraffin wax Substances 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 230000035755 proliferation Effects 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 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 5
- 239000013603 viral vector Substances 0.000 description 5
- 239000000304 virulence factor Substances 0.000 description 5
- 230000007923 virulence factor Effects 0.000 description 5
- 102000009027 Albumins Human genes 0.000 description 4
- 108010088751 Albumins Proteins 0.000 description 4
- 241000701022 Cytomegalovirus Species 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 4
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- 206010028851 Necrosis Diseases 0.000 description 4
- 206010029803 Nosocomial infection Diseases 0.000 description 4
- 206010057249 Phagocytosis Diseases 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 241000607142 Salmonella Species 0.000 description 4
- 240000005499 Sasa Species 0.000 description 4
- 108010059993 Vancomycin Proteins 0.000 description 4
- 108010031318 Vitronectin Proteins 0.000 description 4
- 102100035140 Vitronectin Human genes 0.000 description 4
- 230000033289 adaptive immune response Effects 0.000 description 4
- 230000006907 apoptotic process Effects 0.000 description 4
- 229940009098 aspartate Drugs 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 230000015271 coagulation Effects 0.000 description 4
- 238000005345 coagulation Methods 0.000 description 4
- 238000000576 coating method Methods 0.000 description 4
- 230000005757 colony formation Effects 0.000 description 4
- 238000001784 detoxification Methods 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 4
- 230000005745 host immune response Effects 0.000 description 4
- 230000001900 immune effect Effects 0.000 description 4
- 230000008595 infiltration Effects 0.000 description 4
- 238000001764 infiltration Methods 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 238000003780 insertion Methods 0.000 description 4
- 230000037431 insertion Effects 0.000 description 4
- 238000007918 intramuscular administration Methods 0.000 description 4
- 229960000310 isoleucine Drugs 0.000 description 4
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 4
- 108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 210000000265 leukocyte Anatomy 0.000 description 4
- 210000004072 lung Anatomy 0.000 description 4
- 239000011159 matrix material Substances 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 230000017074 necrotic cell death Effects 0.000 description 4
- 230000001338 necrotic effect Effects 0.000 description 4
- 230000007935 neutral effect Effects 0.000 description 4
- 230000036963 noncompetitive effect Effects 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 238000007911 parenteral administration Methods 0.000 description 4
- 230000002093 peripheral effect Effects 0.000 description 4
- 230000008782 phagocytosis Effects 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 238000007920 subcutaneous administration Methods 0.000 description 4
- 229940031626 subunit vaccine Drugs 0.000 description 4
- 239000003053 toxin Substances 0.000 description 4
- 231100000765 toxin Toxicity 0.000 description 4
- 108700012359 toxins Proteins 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
- 239000003981 vehicle Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- 101710092462 Alpha-hemolysin Proteins 0.000 description 3
- 101710197219 Alpha-toxin Proteins 0.000 description 3
- 239000004475 Arginine Substances 0.000 description 3
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 3
- 208000031729 Bacteremia Diseases 0.000 description 3
- 108010071134 CRM197 (non-toxic variant of diphtheria toxin) Proteins 0.000 description 3
- 208000035473 Communicable disease Diseases 0.000 description 3
- 206010010356 Congenital anomaly Diseases 0.000 description 3
- 102100037840 Dehydrogenase/reductase SDR family member 2, mitochondrial Human genes 0.000 description 3
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 3
- 108010070675 Glutathione transferase Proteins 0.000 description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 3
- 102100029100 Hematopoietic prostaglandin D synthase Human genes 0.000 description 3
- 102220637909 Histone chaperone ASF1B_D36A_mutation Human genes 0.000 description 3
- 102220637910 Histone chaperone ASF1B_D37A_mutation Human genes 0.000 description 3
- 101000651439 Homo sapiens Prothrombin Proteins 0.000 description 3
- 206010061217 Infestation Diseases 0.000 description 3
- 102000013462 Interleukin-12 Human genes 0.000 description 3
- 108010065805 Interleukin-12 Proteins 0.000 description 3
- 108010002350 Interleukin-2 Proteins 0.000 description 3
- 102000000588 Interleukin-2 Human genes 0.000 description 3
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 3
- 101710087657 Manganese ABC transporter substrate-binding lipoprotein Proteins 0.000 description 3
- 208000037942 Methicillin-resistant Staphylococcus aureus infection Diseases 0.000 description 3
- 102000057297 Pepsin A Human genes 0.000 description 3
- 108090000284 Pepsin A Proteins 0.000 description 3
- 101710124951 Phospholipase C Proteins 0.000 description 3
- 101710188053 Protein D Proteins 0.000 description 3
- 108010029485 Protein Isoforms Proteins 0.000 description 3
- 102000001708 Protein Isoforms Human genes 0.000 description 3
- 101710132893 Resolvase Proteins 0.000 description 3
- 229920002684 Sepharose Polymers 0.000 description 3
- 102000054727 Serum Amyloid A Human genes 0.000 description 3
- 108700028909 Serum Amyloid A Proteins 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 108091008874 T cell receptors Proteins 0.000 description 3
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 3
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 description 3
- 102220500923 Telomerase reverse transcriptase_K35D_mutation Human genes 0.000 description 3
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 3
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 3
- 102220575134 Uncharacterized protein MISP3_I31A_mutation Human genes 0.000 description 3
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000003213 activating effect Effects 0.000 description 3
- 239000002776 alpha toxin Substances 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000001640 apoptogenic effect Effects 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 3
- 235000009582 asparagine Nutrition 0.000 description 3
- 229960001230 asparagine Drugs 0.000 description 3
- CKLJMWTZIZZHCS-REOHCLBHSA-L aspartate group Chemical class N[C@@H](CC(=O)[O-])C(=O)[O-] CKLJMWTZIZZHCS-REOHCLBHSA-L 0.000 description 3
- 238000011888 autopsy Methods 0.000 description 3
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 3
- 230000000903 blocking effect Effects 0.000 description 3
- 230000023555 blood coagulation Effects 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 230000004663 cell proliferation Effects 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 230000002950 deficient Effects 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 206010014665 endocarditis Diseases 0.000 description 3
- 230000002708 enhancing effect Effects 0.000 description 3
- 101150016690 esxA gene Proteins 0.000 description 3
- 101150079015 esxB gene Proteins 0.000 description 3
- 210000003527 eukaryotic cell Anatomy 0.000 description 3
- 230000004927 fusion Effects 0.000 description 3
- 229960002442 glucosamine Drugs 0.000 description 3
- 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 229940039715 human prothrombin Drugs 0.000 description 3
- 230000008348 humoral response Effects 0.000 description 3
- 210000002865 immune cell Anatomy 0.000 description 3
- 210000000987 immune system Anatomy 0.000 description 3
- 229940127121 immunoconjugate Drugs 0.000 description 3
- 230000002458 infectious effect Effects 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 230000002452 interceptive effect Effects 0.000 description 3
- 238000007912 intraperitoneal administration Methods 0.000 description 3
- 229910052742 iron Inorganic materials 0.000 description 3
- 230000004807 localization Effects 0.000 description 3
- 239000006166 lysate Substances 0.000 description 3
- 210000002540 macrophage Anatomy 0.000 description 3
- 210000003622 mature neutrocyte Anatomy 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 229940035032 monophosphoryl lipid a Drugs 0.000 description 3
- 238000002703 mutagenesis Methods 0.000 description 3
- 231100000350 mutagenesis Toxicity 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 229940111202 pepsin Drugs 0.000 description 3
- 230000002688 persistence Effects 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 230000003449 preventive effect Effects 0.000 description 3
- 210000001236 prokaryotic cell Anatomy 0.000 description 3
- 238000011321 prophylaxis Methods 0.000 description 3
- 238000011002 quantification Methods 0.000 description 3
- 230000003252 repetitive effect Effects 0.000 description 3
- 230000000717 retained effect Effects 0.000 description 3
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 208000004048 staphylococcal pneumonia Diseases 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 230000002459 sustained effect Effects 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 230000032258 transport Effects 0.000 description 3
- 239000001974 tryptic soy broth Substances 0.000 description 3
- 108010050327 trypticase-soy broth Proteins 0.000 description 3
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 3
- 239000004474 valine Substances 0.000 description 3
- 230000003612 virological effect Effects 0.000 description 3
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 2
- DIGQNXIGRZPYDK-WKSCXVIASA-N (2R)-6-amino-2-[[2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-[[(2R,3S)-2-[[2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S,3S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2R)-2-[[2-[[2-[[2-[(2-amino-1-hydroxyethylidene)amino]-3-carboxy-1-hydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1,5-dihydroxy-5-iminopentylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]hexanoic acid Chemical compound C[C@@H]([C@@H](C(=N[C@@H](CS)C(=N[C@@H](C)C(=N[C@@H](CO)C(=NCC(=N[C@@H](CCC(=N)O)C(=NC(CS)C(=N[C@H]([C@H](C)O)C(=N[C@H](CS)C(=N[C@H](CO)C(=NCC(=N[C@H](CS)C(=NCC(=N[C@H](CCCCN)C(=O)O)O)O)O)O)O)O)O)O)O)O)O)O)O)N=C([C@H](CS)N=C([C@H](CO)N=C([C@H](CO)N=C([C@H](C)N=C(CN=C([C@H](CO)N=C([C@H](CS)N=C(CN=C(C(CS)N=C(C(CC(=O)O)N=C(CN)O)O)O)O)O)O)O)O)O)O)O)O DIGQNXIGRZPYDK-WKSCXVIASA-N 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 2
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 2
- RADQQIMFQHYCBI-UHFFFAOYSA-N 6-[[4-[2-[2-[2-acetamido-4-[3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-5,6-dihydroxy-1-oxohexan-3-yl]oxypropanoylamino]propanoylamino]-4-carboxybutanoyl]amino]-2-amino-7-(1-carboxyethylamino)-7-oxoheptanoic acid Chemical compound OC(=O)C(N)CCCC(C(=O)NC(C)C(O)=O)NC(=O)CCC(C(O)=O)NC(=O)C(C)NC(=O)C(C)OC(C(NC(C)=O)C=O)C(C(O)CO)OC1OC(CO)C(O)C(O)C1NC(C)=O RADQQIMFQHYCBI-UHFFFAOYSA-N 0.000 description 2
- 102220510663 APC membrane recruitment protein 1_Y18F_mutation Human genes 0.000 description 2
- 101100128225 Bacillus subtilis (strain 168) licT gene Proteins 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 108010039939 Cell Wall Skeleton Proteins 0.000 description 2
- 102100029057 Coagulation factor XIII A chain Human genes 0.000 description 2
- 102220554118 Cyclic GMP-AMP synthase_L21H_mutation Human genes 0.000 description 2
- 102220570828 Deoxynucleotidyltransferase terminal-interacting protein 1_Y14A_mutation Human genes 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- 238000012286 ELISA Assay Methods 0.000 description 2
- 108700041152 Endoplasmic Reticulum Chaperone BiP Proteins 0.000 description 2
- 102100021451 Endoplasmic reticulum chaperone BiP Human genes 0.000 description 2
- 241000194033 Enterococcus Species 0.000 description 2
- 241000283086 Equidae Species 0.000 description 2
- 241001198387 Escherichia coli BL21(DE3) Species 0.000 description 2
- 108050001049 Extracellular proteins Proteins 0.000 description 2
- 241000233866 Fungi Species 0.000 description 2
- 102000006395 Globulins Human genes 0.000 description 2
- 108010044091 Globulins Proteins 0.000 description 2
- 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 2
- 239000004471 Glycine Substances 0.000 description 2
- 102000003886 Glycoproteins Human genes 0.000 description 2
- 108090000288 Glycoproteins Proteins 0.000 description 2
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 2
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 2
- 101150112743 HSPA5 gene Proteins 0.000 description 2
- 241000606768 Haemophilus influenzae Species 0.000 description 2
- 208000032843 Hemorrhage Diseases 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- 101000918352 Homo sapiens Coagulation factor XIII A chain Proteins 0.000 description 2
- 102000004157 Hydrolases Human genes 0.000 description 2
- 108090000604 Hydrolases Proteins 0.000 description 2
- 206010061598 Immunodeficiency Diseases 0.000 description 2
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 2
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 2
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 2
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 2
- 108010074328 Interferon-gamma Proteins 0.000 description 2
- 102000008070 Interferon-gamma Human genes 0.000 description 2
- 102000004388 Interleukin-4 Human genes 0.000 description 2
- 108090000978 Interleukin-4 Proteins 0.000 description 2
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 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
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-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
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- 102000043136 MAP kinase family Human genes 0.000 description 2
- 108091054455 MAP kinase family Proteins 0.000 description 2
- 108091054437 MHC class I family Proteins 0.000 description 2
- 102000043131 MHC class II family Human genes 0.000 description 2
- 108091054438 MHC class II family Proteins 0.000 description 2
- 108010059343 MM Form Creatine Kinase Proteins 0.000 description 2
- 102220641747 Metalloproteinase inhibitor 1_Q32A_mutation Human genes 0.000 description 2
- 102000003792 Metallothionein Human genes 0.000 description 2
- 108090000157 Metallothionein Proteins 0.000 description 2
- 241000713333 Mouse mammary tumor virus Species 0.000 description 2
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 2
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 2
- 125000003047 N-acetyl group Chemical group 0.000 description 2
- 102220532965 NEDD8-conjugating enzyme Ubc12_F5A_mutation Human genes 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 102000005608 Neuronal Cell Adhesion Molecules Human genes 0.000 description 2
- 108010059604 Neuronal Cell Adhesion Molecules Proteins 0.000 description 2
- 102220580238 Non-receptor tyrosine-protein kinase TYK2_Q13A_mutation Human genes 0.000 description 2
- 241001452677 Ogataea methanolica Species 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- 102220566933 Oligosaccharyltransferase complex subunit OSTC_L17A_mutation Human genes 0.000 description 2
- 102220566947 Oligosaccharyltransferase complex subunit OSTC_N28A_mutation Human genes 0.000 description 2
- 108700026244 Open Reading Frames Proteins 0.000 description 2
- 108700022034 Opsonin Proteins Proteins 0.000 description 2
- 101100103787 Oryza sativa subsp. japonica Y14A gene Proteins 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- 108090000279 Peptidyltransferases Proteins 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 2
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 239000004793 Polystyrene Substances 0.000 description 2
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 2
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- 101100111629 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) KAR2 gene Proteins 0.000 description 2
- 108010071390 Serum Albumin Proteins 0.000 description 2
- 102000007562 Serum Albumin Human genes 0.000 description 2
- 101000794214 Staphylococcus aureus Toxic shock syndrome toxin-1 Proteins 0.000 description 2
- 241000191963 Staphylococcus epidermidis Species 0.000 description 2
- 108091081024 Start codon Proteins 0.000 description 2
- 238000000692 Student's t-test Methods 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- 239000004098 Tetracycline Substances 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Substances 0.000 description 2
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
- 102220497186 WD repeat domain phosphoinositide-interacting protein 4_N15A_mutation Human genes 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
- 210000000683 abdominal cavity Anatomy 0.000 description 2
- 235000011054 acetic acid Nutrition 0.000 description 2
- 230000021736 acetylation Effects 0.000 description 2
- 238000006640 acetylation reaction Methods 0.000 description 2
- 230000000240 adjuvant effect Effects 0.000 description 2
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 2
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 210000000612 antigen-presenting cell Anatomy 0.000 description 2
- 239000012736 aqueous medium Substances 0.000 description 2
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 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 2
- 230000005540 biological transmission Effects 0.000 description 2
- 208000037815 bloodstream infection Diseases 0.000 description 2
- 210000001124 body fluid Anatomy 0.000 description 2
- 239000010839 body fluid Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 239000003518 caustics Substances 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000032823 cell division Effects 0.000 description 2
- 210000004520 cell wall skeleton Anatomy 0.000 description 2
- 230000036755 cellular response Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 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
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 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 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
- 230000001332 colony forming effect Effects 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 239000003431 cross linking reagent Substances 0.000 description 2
- 210000000805 cytoplasm Anatomy 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 229960003983 diphtheria toxoid Drugs 0.000 description 2
- 108700033544 disaccharide tetrapeptide Proteins 0.000 description 2
- 239000002612 dispersion medium Substances 0.000 description 2
- 238000010494 dissociation reaction Methods 0.000 description 2
- 230000005593 dissociations Effects 0.000 description 2
- 230000009977 dual effect Effects 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 238000004945 emulsification Methods 0.000 description 2
- 239000002158 endotoxin Substances 0.000 description 2
- 230000002327 eosinophilic effect Effects 0.000 description 2
- 101150043366 essB gene Proteins 0.000 description 2
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 2
- 230000003325 follicular Effects 0.000 description 2
- 238000005194 fractionation Methods 0.000 description 2
- 229940044627 gamma-interferon Drugs 0.000 description 2
- 238000012224 gene deletion Methods 0.000 description 2
- MSWZFWKMSRAUBD-IVMDWMLBSA-N glucosamine group Chemical group OC1[C@H](N)[C@@H](O)[C@H](O)[C@H](O1)CO MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 2
- 108010017007 glucose-regulated proteins Proteins 0.000 description 2
- 229930195712 glutamate Natural products 0.000 description 2
- 239000005090 green fluorescent protein Substances 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 101150028578 grp78 gene Proteins 0.000 description 2
- 229940047650 haemophilus influenzae Drugs 0.000 description 2
- 230000003118 histopathologic effect Effects 0.000 description 2
- 210000005260 human cell Anatomy 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 230000007124 immune defense Effects 0.000 description 2
- 238000003119 immunoblot Methods 0.000 description 2
- 230000016784 immunoglobulin production Effects 0.000 description 2
- 230000003308 immunostimulating effect Effects 0.000 description 2
- 239000002054 inoculum Substances 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 229940079322 interferon Drugs 0.000 description 2
- 238000010255 intramuscular injection Methods 0.000 description 2
- 239000007927 intramuscular injection Substances 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 229960003299 ketamine Drugs 0.000 description 2
- 230000002147 killing effect Effects 0.000 description 2
- 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 229960002510 mandelic acid Drugs 0.000 description 2
- 238000013507 mapping Methods 0.000 description 2
- 208000004396 mastitis Diseases 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- 238000000386 microscopy Methods 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 102000035118 modified proteins Human genes 0.000 description 2
- 108091005573 modified proteins Proteins 0.000 description 2
- 210000000440 neutrophil Anatomy 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 238000000399 optical microscopy Methods 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 235000006408 oxalic acid Nutrition 0.000 description 2
- 230000000242 pagocytic effect Effects 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 230000002085 persistent effect Effects 0.000 description 2
- 210000001539 phagocyte Anatomy 0.000 description 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 2
- 230000004481 post-translational protein modification Effects 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 238000003127 radioimmunoassay Methods 0.000 description 2
- 238000010188 recombinant method Methods 0.000 description 2
- 230000006798 recombination Effects 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 230000003362 replicative effect Effects 0.000 description 2
- 102220278552 rs1554434768 Human genes 0.000 description 2
- 102220050582 rs193920899 Human genes 0.000 description 2
- 102220011660 rs63751099 Human genes 0.000 description 2
- 102220057217 rs730881149 Human genes 0.000 description 2
- 210000003296 saliva Anatomy 0.000 description 2
- 238000004626 scanning electron microscopy Methods 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 230000003248 secreting effect Effects 0.000 description 2
- 125000006850 spacer group Chemical group 0.000 description 2
- 210000004989 spleen cell Anatomy 0.000 description 2
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 238000003860 storage Methods 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
- 108020001568 subdomains Proteins 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 238000012353 t test Methods 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- 150000003505 terpenes Chemical class 0.000 description 2
- 235000007586 terpenes Nutrition 0.000 description 2
- 229960002180 tetracycline Drugs 0.000 description 2
- 229930101283 tetracycline Natural products 0.000 description 2
- 235000019364 tetracycline Nutrition 0.000 description 2
- 150000003522 tetracyclines Chemical class 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 231100000563 toxic property Toxicity 0.000 description 2
- 230000014616 translation Effects 0.000 description 2
- XETCRXVKJHBPMK-MJSODCSWSA-N trehalose 6,6'-dimycolate Chemical compound C([C@@H]1[C@H]([C@H](O)[C@@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](COC(=O)C(CCCCCCCCCCC3C(C3)CCCCCCCCCCCCCCCCCC)C(O)CCCCCCCCCCCCCCCCCCCCCCCCC)O2)O)O1)O)OC(=O)C(C(O)CCCCCCCCCCCCCCCCCCCCCCCCC)CCCCCCCCCCC1CC1CCCCCCCCCCCCCCCCCC XETCRXVKJHBPMK-MJSODCSWSA-N 0.000 description 2
- 150000003626 triacylglycerols Chemical class 0.000 description 2
- IEDVJHCEMCRBQM-UHFFFAOYSA-N trimethoprim Chemical compound COC1=C(OC)C(OC)=CC(CC=2C(=NC(N)=NC=2)N)=C1 IEDVJHCEMCRBQM-UHFFFAOYSA-N 0.000 description 2
- 229960001082 trimethoprim Drugs 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 241000701447 unidentified baculovirus Species 0.000 description 2
- 230000035899 viability Effects 0.000 description 2
- 230000001018 virulence Effects 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- LLXVXPPXELIDGQ-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-(2,5-dioxopyrrol-1-yl)benzoate Chemical compound C=1C=CC(N2C(C=CC2=O)=O)=CC=1C(=O)ON1C(=O)CCC1=O LLXVXPPXELIDGQ-UHFFFAOYSA-N 0.000 description 1
- BNGXYYYYKUGPPF-UHFFFAOYSA-M (3-methylphenyl)methyl-triphenylphosphanium;chloride Chemical compound [Cl-].CC1=CC=CC(C[P+](C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 BNGXYYYYKUGPPF-UHFFFAOYSA-M 0.000 description 1
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
- SGKRLCUYIXIAHR-AKNGSSGZSA-N (4s,4ar,5s,5ar,6r,12ar)-4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1=CC=C2[C@H](C)[C@@H]([C@H](O)[C@@H]3[C@](C(O)=C(C(N)=O)C(=O)[C@H]3N(C)C)(O)C3=O)C3=C(O)C2=C1O SGKRLCUYIXIAHR-AKNGSSGZSA-N 0.000 description 1
- YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 description 1
- QZCJOXAIQXPLNS-UHFFFAOYSA-N 1,1,2,2,3,3,4,4,4a,5,5,6,6,7,7,8,8,8a-octadecafluoronaphthalene 4-(2-aminoethyl)benzene-1,2-diol Chemical compound NCCc1ccc(O)c(O)c1.FC1(F)C(F)(F)C(F)(F)C2(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C2(F)C1(F)F QZCJOXAIQXPLNS-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- STOVYWBRBMYHPC-KAVGSWPWSA-N 2-[(E)-[(E)-(2-hydroxyphenyl)methylidenehydrazinylidene]methyl]phenol Chemical compound OC1=CC=CC=C1\C=N\N=C\C1=CC=CC=C1O STOVYWBRBMYHPC-KAVGSWPWSA-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
- 238000010600 3H thymidine incorporation assay Methods 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical group CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 241001156739 Actinobacteria <phylum> Species 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 108010024223 Adenine phosphoribosyltransferase Proteins 0.000 description 1
- 241000664917 Aedes pia Species 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- 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 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 206010053555 Arthritis bacterial Diseases 0.000 description 1
- 241000711404 Avian avulavirus 1 Species 0.000 description 1
- 230000024704 B cell apoptotic process Effects 0.000 description 1
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 1
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 241000197194 Bulla Species 0.000 description 1
- 241001260012 Bursa Species 0.000 description 1
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
- 238000011746 C57BL/6J (JAX™ mouse strain) Methods 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 108010076119 Caseins Proteins 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 101710163595 Chaperone protein DnaK Proteins 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 241000675108 Citrus tangerina Species 0.000 description 1
- 206010053567 Coagulopathies Diseases 0.000 description 1
- 108700010070 Codon Usage Proteins 0.000 description 1
- 102000012422 Collagen Type I Human genes 0.000 description 1
- 108010022452 Collagen Type I Proteins 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 206010011409 Cross infection Diseases 0.000 description 1
- 101710095468 Cyclase Proteins 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 150000008574 D-amino acids Chemical class 0.000 description 1
- 101150074155 DHFR gene Proteins 0.000 description 1
- 108010041986 DNA Vaccines Proteins 0.000 description 1
- 229940021995 DNA vaccine Drugs 0.000 description 1
- 102220557633 DNA-directed RNA polymerase I subunit RPA12_Q14H_mutation Human genes 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 229940032046 DTaP vaccine Drugs 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 206010013801 Duchenne Muscular Dystrophy Diseases 0.000 description 1
- 101710178629 ESAT-6-like protein Proteins 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 102100039328 Endoplasmin Human genes 0.000 description 1
- 102220508665 Ephrin type-A receptor 4_Q40A_mutation Human genes 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
- 241000283074 Equus asinus Species 0.000 description 1
- ITIONVBQFUNVJV-UHFFFAOYSA-N Etomidoline Chemical compound C12=CC=CC=C2C(=O)N(CC)C1NC(C=C1)=CC=C1OCCN1CCCCC1 ITIONVBQFUNVJV-UHFFFAOYSA-N 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 206010053172 Fatal outcomes Diseases 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
- 208000019331 Foodborne disease Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 101100010809 Geobacillus thermodenitrificans (strain NG80-2) eccC gene Proteins 0.000 description 1
- 229930186217 Glycolipid Natural products 0.000 description 1
- 108010062347 HLA-DQ Antigens Proteins 0.000 description 1
- 101001015673 Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd) Glycerophosphodiester phosphodiesterase Proteins 0.000 description 1
- 101710178376 Heat shock 70 kDa protein Proteins 0.000 description 1
- 101710152018 Heat shock cognate 70 kDa protein Proteins 0.000 description 1
- 101710154606 Hemagglutinin Proteins 0.000 description 1
- 102100021519 Hemoglobin subunit beta Human genes 0.000 description 1
- 108091005904 Hemoglobin subunit beta Proteins 0.000 description 1
- 108091005886 Hemoglobin subunit gamma Proteins 0.000 description 1
- 102100038617 Hemoglobin subunit gamma-2 Human genes 0.000 description 1
- 241000700721 Hepatitis B virus Species 0.000 description 1
- 102000008949 Histocompatibility Antigens Class I Human genes 0.000 description 1
- 108010033040 Histones Proteins 0.000 description 1
- 101000702559 Homo sapiens Probable global transcription activator SNF2L2 Proteins 0.000 description 1
- 101001050288 Homo sapiens Transcription factor Jun Proteins 0.000 description 1
- 241001135569 Human adenovirus 5 Species 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 241000282620 Hylobates sp. Species 0.000 description 1
- 108010091358 Hypoxanthine Phosphoribosyltransferase Proteins 0.000 description 1
- 102100029098 Hypoxanthine-guanine phosphoribosyltransferase Human genes 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 1
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 1
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 1
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 1
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 1
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 208000004575 Infectious Arthritis Diseases 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 102100025306 Integrin alpha-IIb Human genes 0.000 description 1
- 101710149643 Integrin alpha-IIb Proteins 0.000 description 1
- 108090000467 Interferon-beta Proteins 0.000 description 1
- 102000003996 Interferon-beta Human genes 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 102000000589 Interleukin-1 Human genes 0.000 description 1
- 108090000174 Interleukin-10 Proteins 0.000 description 1
- 102000010789 Interleukin-2 Receptors Human genes 0.000 description 1
- 108010038453 Interleukin-2 Receptors Proteins 0.000 description 1
- 108010002616 Interleukin-5 Proteins 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 108010002586 Interleukin-7 Proteins 0.000 description 1
- 102000000704 Interleukin-7 Human genes 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 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
- 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 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
- 241000194036 Lactococcus Species 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 101710128836 Large T antigen Proteins 0.000 description 1
- 208000032376 Lung infection Diseases 0.000 description 1
- UPYKUZBSLRQECL-UKMVMLAPSA-N Lycopene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1C(=C)CCCC1(C)C)C=CC=C(/C)C=CC2C(=C)CCCC2(C)C UPYKUZBSLRQECL-UKMVMLAPSA-N 0.000 description 1
- JEVVKJMRZMXFBT-XWDZUXABSA-N Lycophyll Natural products OC/C(=C/CC/C(=C\C=C\C(=C/C=C/C(=C\C=C\C=C(/C=C/C=C(\C=C\C=C(/CC/C=C(/CO)\C)\C)/C)\C)/C)\C)/C)/C JEVVKJMRZMXFBT-XWDZUXABSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 101710201349 Metallothionein B Proteins 0.000 description 1
- 102100031347 Metallothionein-2 Human genes 0.000 description 1
- 101710094505 Metallothionein-2 Proteins 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 102100035971 Molybdopterin molybdenumtransferase Human genes 0.000 description 1
- 101710119577 Molybdopterin molybdenumtransferase Proteins 0.000 description 1
- 102000016943 Muramidase Human genes 0.000 description 1
- 108010014251 Muramidase Proteins 0.000 description 1
- 101100078999 Mus musculus Mx1 gene Proteins 0.000 description 1
- 101000854604 Mus musculus Protein FAM167B Proteins 0.000 description 1
- 101000651440 Mus musculus Prothrombin Proteins 0.000 description 1
- 101000836210 Mus musculus Somatotropin Proteins 0.000 description 1
- 101100445609 Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) espC gene Proteins 0.000 description 1
- 102220532634 NEDD8-conjugating enzyme Ubc12_Q10A_mutation Human genes 0.000 description 1
- 101100257820 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) ssp-1 gene Proteins 0.000 description 1
- 108091005461 Nucleic proteins Chemical group 0.000 description 1
- 206010031252 Osteomyelitis Diseases 0.000 description 1
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 1
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 1
- 108010067372 Pancreatic elastase Proteins 0.000 description 1
- 102000016387 Pancreatic elastase Human genes 0.000 description 1
- 241001631646 Papillomaviridae Species 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 241001494479 Pecora 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
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 102100034173 Platelet glycoprotein Ib alpha chain Human genes 0.000 description 1
- 101710107770 Platelet glycoprotein Ib alpha chain Proteins 0.000 description 1
- 101710183389 Pneumolysin Proteins 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 108010071690 Prealbumin Proteins 0.000 description 1
- 102000007584 Prealbumin Human genes 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 102100031021 Probable global transcription activator SNF2L2 Human genes 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 101710176177 Protein A56 Proteins 0.000 description 1
- 102000007568 Proto-Oncogene Proteins c-fos Human genes 0.000 description 1
- 108010071563 Proto-Oncogene Proteins c-fos Proteins 0.000 description 1
- 206010040070 Septic Shock Diseases 0.000 description 1
- 206010040914 Skin reaction Diseases 0.000 description 1
- 206010062255 Soft tissue infection Diseases 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 240000006394 Sorghum bicolor Species 0.000 description 1
- 235000011684 Sorghum saccharatum Nutrition 0.000 description 1
- 241000160646 Sporidesmium parvum Species 0.000 description 1
- 206010041917 Staphylococcal abscess Diseases 0.000 description 1
- 101100280079 Staphylococcus aureus (strain Mu50 / ATCC 700699) esxA gene Proteins 0.000 description 1
- 101100280095 Staphylococcus aureus (strain Mu50 / ATCC 700699) esxB gene Proteins 0.000 description 1
- 101100233392 Staphylococcus aureus (strain Mu50 / ATCC 700699) isdA gene Proteins 0.000 description 1
- 101100019123 Staphylococcus aureus (strain Mu50 / ATCC 700699) isdB gene Proteins 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 208000002847 Surgical Wound Diseases 0.000 description 1
- 208000031650 Surgical Wound Infection Diseases 0.000 description 1
- 241001185310 Symbiotes <prokaryote> Species 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 230000024932 T cell mediated immunity Effects 0.000 description 1
- 230000006052 T cell proliferation Effects 0.000 description 1
- 108090000925 TNF receptor-associated factor 2 Proteins 0.000 description 1
- 102100034779 TRAF family member-associated NF-kappa-B activator Human genes 0.000 description 1
- 102220500149 Target of EGR1 protein 1_Q9A_mutation Human genes 0.000 description 1
- 108020005038 Terminator Codon Proteins 0.000 description 1
- 206010043376 Tetanus Diseases 0.000 description 1
- BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 229940122388 Thrombin inhibitor Drugs 0.000 description 1
- 102000006601 Thymidine Kinase Human genes 0.000 description 1
- 108020004440 Thymidine kinase Proteins 0.000 description 1
- 102220470366 Thymosin beta-10_F30A_mutation Human genes 0.000 description 1
- 102000011923 Thyrotropin Human genes 0.000 description 1
- 108010061174 Thyrotropin Proteins 0.000 description 1
- 101150009046 Tnfrsf1a gene Proteins 0.000 description 1
- 206010044248 Toxic shock syndrome Diseases 0.000 description 1
- 231100000650 Toxic shock syndrome Toxicity 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 102100023132 Transcription factor Jun Human genes 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 102000013394 Troponin I Human genes 0.000 description 1
- 108010065729 Troponin I Proteins 0.000 description 1
- 102220549960 Usher syndrome type-1C protein-binding protein 1_N21A_mutation Human genes 0.000 description 1
- 206010046865 Vaccinia virus infection Diseases 0.000 description 1
- LUXUAZKGQZPOBZ-SAXJAHGMSA-N [(3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] (Z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC1O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]1O LUXUAZKGQZPOBZ-SAXJAHGMSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000003070 absorption delaying agent Substances 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000002730 additional effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- 108091006055 affinity-tagged proteins Proteins 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- NWMHDZMRVUOQGL-CZEIJOLGSA-N almurtide Chemical compound OC(=O)CC[C@H](C(N)=O)NC(=O)[C@H](C)NC(=O)CO[C@@H]([C@H](O)[C@H](O)CO)[C@@H](NC(C)=O)C=O NWMHDZMRVUOQGL-CZEIJOLGSA-N 0.000 description 1
- 101150087698 alpha gene Proteins 0.000 description 1
- 102000013529 alpha-Fetoproteins Human genes 0.000 description 1
- 108010026331 alpha-Fetoproteins Proteins 0.000 description 1
- 229940037003 alum Drugs 0.000 description 1
- ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 description 1
- 150000003862 amino acid derivatives Chemical class 0.000 description 1
- 229940126575 aminoglycoside Drugs 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 238000011203 antimicrobial therapy Methods 0.000 description 1
- 210000004507 artificial chromosome Anatomy 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- 230000001746 atrial effect Effects 0.000 description 1
- 210000000649 b-lymphocyte subset Anatomy 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 210000003651 basophil Anatomy 0.000 description 1
- HFACYLZERDEVSX-UHFFFAOYSA-N benzidine Chemical compound C1=CC(N)=CC=C1C1=CC=C(N)C=C1 HFACYLZERDEVSX-UHFFFAOYSA-N 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 208000002352 blister Diseases 0.000 description 1
- 239000003114 blood coagulation factor Substances 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000002798 bone marrow cell Anatomy 0.000 description 1
- 235000021152 breakfast Nutrition 0.000 description 1
- LIMQQADUEULBSO-UHFFFAOYSA-N butyl isothiocyanate Chemical compound CCCCN=C=S LIMQQADUEULBSO-UHFFFAOYSA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 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
- 210000000711 cavernous sinus Anatomy 0.000 description 1
- 210000004970 cd4 cell Anatomy 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 230000007969 cellular immunity Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 239000012707 chemical precursor Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000003593 chromogenic compound Substances 0.000 description 1
- CCGSUNCLSOWKJO-UHFFFAOYSA-N cimetidine Chemical compound N#CNC(=N/C)\NCCSCC1=NC=N[C]1C CCGSUNCLSOWKJO-UHFFFAOYSA-N 0.000 description 1
- 229960001380 cimetidine Drugs 0.000 description 1
- 229960003405 ciprofloxacin Drugs 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 230000035602 clotting Effects 0.000 description 1
- 239000000701 coagulant Substances 0.000 description 1
- 230000006448 coagulant property Effects 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 230000001268 conjugating effect Effects 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000011443 conventional therapy Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 206010013023 diphtheria Diseases 0.000 description 1
- 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 1
- 230000006806 disease prevention Effects 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 229960003722 doxycycline Drugs 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000012149 elution buffer Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000008393 encapsulating agent Substances 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 210000003979 eosinophil Anatomy 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 101150022827 esaA gene Proteins 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 101150102084 essA gene Proteins 0.000 description 1
- 101150018154 essC gene Proteins 0.000 description 1
- 101150026034 esxC gene Proteins 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 239000002350 fibrinopeptide Substances 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
- 239000012530 fluid Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 238000001502 gel electrophoresis Methods 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
- 108091008053 gene clusters Proteins 0.000 description 1
- 238000001476 gene delivery Methods 0.000 description 1
- 102000034356 gene-regulatory proteins Human genes 0.000 description 1
- 108091006104 gene-regulatory proteins Proteins 0.000 description 1
- 230000009395 genetic defect Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000011331 genomic analysis Methods 0.000 description 1
- 229960002518 gentamicin Drugs 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 150000003278 haem Chemical class 0.000 description 1
- 210000003709 heart valve Anatomy 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 239000000185 hemagglutinin Substances 0.000 description 1
- 108060003552 hemocyanin Proteins 0.000 description 1
- 108010037896 heparin-binding hemagglutinin Proteins 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- HWFSCNOWKORLGJ-UHFFFAOYSA-N hexanedioic acid;dihydrate Chemical compound O.O.OC(=O)CCCCC(O)=O HWFSCNOWKORLGJ-UHFFFAOYSA-N 0.000 description 1
- 238000010562 histological examination Methods 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 230000009215 host defense mechanism Effects 0.000 description 1
- 229940106780 human fibrinogen Drugs 0.000 description 1
- 244000052637 human pathogen Species 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 230000000521 hyperimmunizing effect Effects 0.000 description 1
- 210000001822 immobilized cell Anatomy 0.000 description 1
- 230000000984 immunochemical effect Effects 0.000 description 1
- 238000003365 immunocytochemistry Methods 0.000 description 1
- 238000013115 immunohistochemical detection Methods 0.000 description 1
- 238000011532 immunohistochemical staining Methods 0.000 description 1
- 239000000677 immunologic agent Substances 0.000 description 1
- 229940124541 immunological agent Drugs 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 230000001024 immunotherapeutic effect Effects 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000006882 induction of apoptosis Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 239000002085 irritant Substances 0.000 description 1
- 231100000021 irritant Toxicity 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000004816 latex Substances 0.000 description 1
- 229920000126 latex Polymers 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 230000021633 leukocyte mediated immunity Effects 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
- 239000006193 liquid solution Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 238000001325 log-rank test Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 229960004999 lycopene Drugs 0.000 description 1
- OAIJSZIZWZSQBC-GYZMGTAESA-N lycopene Chemical compound CC(C)=CCC\C(C)=C\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C=C(/C)CCC=C(C)C OAIJSZIZWZSQBC-GYZMGTAESA-N 0.000 description 1
- 235000012661 lycopene Nutrition 0.000 description 1
- 239000001751 lycopene Substances 0.000 description 1
- 238000002794 lymphocyte assay Methods 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
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 1
- JMUHBNWAORSSBD-WKYWBUFDSA-N mifamurtide Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCCCCCCCCCC)COP(O)(=O)OCCNC(=O)[C@H](C)NC(=O)CC[C@H](C(N)=O)NC(=O)[C@H](C)NC(=O)[C@@H](C)O[C@H]1[C@H](O)[C@@H](CO)OC(O)[C@@H]1NC(C)=O JMUHBNWAORSSBD-WKYWBUFDSA-N 0.000 description 1
- 229960005225 mifamurtide Drugs 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 230000004001 molecular interaction Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 229960000951 mycophenolic acid Drugs 0.000 description 1
- HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 244000039328 opportunistic pathogen Species 0.000 description 1
- 210000003463 organelle Anatomy 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000000399 orthopedic effect Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 239000006174 pH buffer Substances 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 229940023041 peptide vaccine Drugs 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 210000003200 peritoneal cavity Anatomy 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 229920002704 polyhistidine Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- 230000001323 posttranslational effect Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 230000006916 protein interaction Effects 0.000 description 1
- 230000009145 protein modification Effects 0.000 description 1
- 229940023143 protein vaccine Drugs 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000007420 reactivation Effects 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 206010038351 renal abscess Diseases 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 102220198146 rs1057519886 Human genes 0.000 description 1
- 102220002405 rs121908660 Human genes 0.000 description 1
- 102220117512 rs886041928 Human genes 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 238000003118 sandwich ELISA Methods 0.000 description 1
- 230000000580 secretagogue effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 201000001223 septic arthritis Diseases 0.000 description 1
- 208000013223 septicemia Diseases 0.000 description 1
- 230000009919 sequestration Effects 0.000 description 1
- 230000000405 serological effect Effects 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 206010040872 skin infection Diseases 0.000 description 1
- 230000035483 skin reaction Effects 0.000 description 1
- 231100000430 skin reaction Toxicity 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000002594 sorbent Substances 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 108090000250 sortase A Proteins 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 230000003393 splenic effect Effects 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 229940031439 squalene Drugs 0.000 description 1
- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000011301 standard therapy Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000010613 succinylation reaction Methods 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 229960005404 sulfamethoxazole Drugs 0.000 description 1
- JLKIGFTWXXRPMT-UHFFFAOYSA-N sulphamethoxazole Chemical compound O1C(C)=CC(NS(=O)(=O)C=2C=CC(N)=CC=2)=N1 JLKIGFTWXXRPMT-UHFFFAOYSA-N 0.000 description 1
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 1
- 238000004114 suspension culture Methods 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 229960000814 tetanus toxoid Drugs 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 239000003868 thrombin inhibitor Substances 0.000 description 1
- 239000005495 thyroid hormone Substances 0.000 description 1
- 229940036555 thyroid hormone Drugs 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 231100000721 toxic potential Toxicity 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- ZCIHMQAPACOQHT-ZGMPDRQDSA-N trans-isorenieratene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/c1c(C)ccc(C)c1C)C=CC=C(/C)C=Cc2c(C)ccc(C)c2C ZCIHMQAPACOQHT-ZGMPDRQDSA-N 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 239000013638 trimer Substances 0.000 description 1
- 239000006150 trypticase soy agar 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
- 201000008827 tuberculosis Diseases 0.000 description 1
- 231100000588 tumorigenic Toxicity 0.000 description 1
- 230000000381 tumorigenic effect Effects 0.000 description 1
- 238000013042 tunel staining Methods 0.000 description 1
- 108010087967 type I signal peptidase Proteins 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
- 230000036967 uncompetitive effect Effects 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 208000019206 urinary tract infection Diseases 0.000 description 1
- 208000007089 vaccinia Diseases 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 125000002987 valine group Chemical group [H]N([H])C([H])(C(*)=O)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 238000002424 x-ray crystallography Methods 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
Images
Classifications
-
- 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
- C07K14/305—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Micrococcaceae (F)
- C07K14/31—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Micrococcaceae (F) from Staphylococcus (G)
-
- 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
- A61K39/085—Staphylococcus
-
- 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
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- 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
-
- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Mycology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Zoology (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
Description
도 1A-1E. 비-독소발생성 단백질 A 백신의 생성. 도 1A는 N-말단 신호 펩타이드 (백색 박스), 5개의 면역글로불린 결합 도메인 (IgBD E, D, A, B 및 C), 가변 영역 X 및 C-말단 분류 신호 (검정 박스)을 갖는 에스. 아우레우스 뉴만 및 USA300 LAC의 전사 단백질 A (SpA) 생성물을 보여준다. 도 1B는 삼중 α-나선 번들 (H1, H2 및 H3)뿐만 아니라 글루타민 (Q) 9, 10 및 아스파르테이트 (D) 36, 37의 위치가 표기되어 있는 5개 IgBD뿐만 아니라 무독소발생성 SpA-DKKAA의 아미노산 서열을 보여준다. 도 1C는 사람 면역글로불린 (hIgG)의 존재 또는 부재하에 Ni-NTA 세파로즈 상에서 정제된 SpA, SpA-D, SpA-DKKAA 또는 SrtA의 쿠마시 블루-염색된 SDS-PAGE를 보여준다. 도 1D는 사람 IgG뿐만 아니라 이의 Fc 또는 F(ab)2 단편 및 폰빌레브란트 (vWF)와 고정된 SpA, SpA-D 또는 SpA-DKKAA의 결합을 검사한 ELISA를 보여준다. 도 1E는 모의 면역화되었거나 SpA-D 또는 SpA-DKKAA로 처리된 BALB/c 마우스의 비장 조직내의 CD19+ B 림프구가 FACS에 의해 정량된 결과를 보여준다.
도 2. 비-독소발생성 단백질 A 백신은 농양 형성을 예방한다. 모의 면역화된 (PBS) 또는 SpA, SpA-D뿐만 아니라 SpA-DKKAA로 백신접종되고 에스. 아우레우스 뉴만으로 시험감염된 BALB/c 마우스의 부검동안에 분리된 비장 조직의 조직병리. 박편된 조직은 헤마톡실린-에오신으로 염색되었다. 백색 화살표는 다형핵 백혈구 (PMN) 침윤물을 가리킨다. 흑색 화살표는 스타필로코커스 농양 군집을 가리킨다.
도 3A-C는 비-독소발생성 단백질 A 백신에 의해 발생된 항체는 SpA의 B 세포 초항원 기능을 차단하는 결과를 보여준다. 도 3A는 SpA-DKKAA에 대해 발생된 토끼 항체가 고정된 항원을 가진 매트릭스에서 정제되고 쿠마시 블루-염색된 SDS-PAGE에 의해 분석된 결과를 보여준다. 항체를 펩신으로 절단하고 F(ab)2 단편을 SpA-DKKAA 매트릭스 상에서 제2 라운드의 친화성 크로마토그래피로 정제하였다. 도 3B는 SpA-DKKAA 특이적 F(ab)2가 사람 면역글로불린 (hIgG)에 SpA 또는 SpA-D의 결합을 방해하는 결과를 보여주며, 도 3C는 폰빌레브란트 인자 (vWF)에의 결합을 방해하는 결과를 보여준다.
도 4A-D는 전체 길이 비-독소발생성 단백질 A가 개량된 면역 반응을 생성함을 보여준다. 도 4A는 전체 길이 SpAKKAA가 Ni-NTA 세파로즈상에서 정제하고 쿠마시-블루 염색된 SDS-PAGE에 의해 분석된 결과를 보여준다. 도 4B는 모의 면역화되었거나 SpA 또는 SpAKKAA로 처리된 BALB/c 마우스의 비장 조직내의 CD19+ B 림프구가 FACS에 의해 정량된 결과를 보여준다. 도 4C는 사람 IgG뿐만 아니라 이의 Fc 또는 F(ab)2 단편 또는 폰빌레브란트 인자 (vWF)와 고정된 SpA 또는 SpAKKAA의 결합을 검사한 ELISA의 결과를 보여준다. 도 4D는 디프테리아 톡소이드 (CRM197) 및 비-독소발생성 SpAKKAA 또는 SpA-DKKAA에 대한 사람 또는 마우스 혈청 항체 역가를 보여준다. DTaP 면역화 및 스타필로코커스 감염의 이력을 갖는 사람 지원자 (n=16) 뿐만 아니라 에스. 아우레우스 뉴만 또는 USA 300 LAC로 감염되었거나 SpAKKAA 또는 SpA-DKKAA로 면역화된 마우스 (n=20)가 정량 도트 블롯에 의해 검사된 결과를 보여준다.
도 5는 마우스에서 치명적인 에스. 아우레우스 감염의 발병을 위해 단백질 A가 필요하다는 것을 보여준다. BALB/c 마우스 코호트 (n=8)에 PBS 중의 2 x 108 CFU 에스. 아우레우스 뉴만 또는 이의 동질유전자형 단백질 A 결실 변이체 (△spa)의 현탁액을 주사하였다. 감염된 동물을 15일간에 걸쳐 생존에 대해 모니터링하였다.
도 6A-B는 단백질 A에 대한 항체가 치명적인 에스. 아우레우스 감염에 대해 마우스를 보호함을 보여준다. 도 6A의 경우, BALB/c 마우스 코호트(n=10)가 SpAKKAA (α-SpAKKAA)에 대해 특이적인 5 mg kg-1 친화성 정제된 토끼 IgG 또는 플라그 백신 항원 rV10 (DeBord et al., 2006)(모의)로 주사되었다. 4시간 후 각 동물은 복강내 주사에 의해 3 x 108 CFU 에스. 아우레우스 뉴만의 현탁액으로 감염되고 10일간에 걸쳐 생존에 대해 모니터링되었다. 데이터는 3회 독립 실험을 대표한 값이다. 도 6B의 경우, BALB/c 마우스 코호트(n=10)가 SpAKKAA 또는 PBS/보조제 대조군 (모의)으로 초기-접종 면역화되었다. 각 동물은 복강내 주사에 의해 6 x 108 CFU 에스. 아우레우스 뉴만의 현택액으로 순차적으로 감염되었고 10일간에 걸쳐 생존에 대해 모니터링되었다. 통계적 유의성 (P)은 짝지워지지 않은 양측 로그 순위 검정으로 분석되었다. 데이터는 모두 3회 독립 실험을 대표한 값이다.
도 7는 SpAKKAA 면역화가 반코마이신-내성 MRSA 분리된 Mu50으로 시험감염한 마우스를 보호한다. BALB/c 마우스 코호트(n=15)는 SpAKKAA 또는 PBS/보조제 대조군 (모의)으로 초기 접종 면역화되었다. 각 동물은 정맥내 주사에 의해 3 x 107 CFU 에스. 아우레우스 Mu50으로 순차적으로 주사되었다. 감염 후 4일 경과하여 균질화된 신장 조직에서 log10 CFU g-1로 계산된 스타필로코커스 부하가 결정되었다. 통계적 유의성은 기록된 짝지워지지 않은 양측 스튜던츠 t-검정으로 계산하고 P 값을 기록하였다.
도 8A-B는 스타필로코커스 감염에 대한 방어 면역 반응의 결여를 보여준다. 도 8A의 경우, 스타필로코커스 감염은 방어 면역성을 발생하지 않는다. BLAB/c 마우스 (n=10)가 30일간 에스. 아우레우스 뉴만으로 감염되었거나 PBS로 모의 시험감염되었고 클로람페니콜 처리로 감염이 제거되었다. 그런 다음 두 동물 코호트는 에스. 아우레우스 뉴만으로 시험감염되었고 4일째 부검하여 신장 조직 균질화물 중의 세균 부하 (CFU)가 분석되었다. 데이터는 3회 독립 분석을 대표하는 값이다. 도 8B의 경우, IsdB 면역화는 에스. 아우레우스 USA300 (LAC) 시험감염에 마우스를 보호하지 못함을 보여준다. BALB/c 마우스 (n=10)는 IsdB로 면역화되었고 (CFA 중에 현탁된 100 ㎍ IsdB에 이어서 11일째 IFA/IsdB 촉진제) 21일째에 5 x 106 CFU 에스. 아우레우스 USA300 (LAC)로 후안 주사에 의해 시험감염되었다. 시험감염 후 4일 경과하여, 부검 동안에 신장을 제거하고 균질화된 조직의 그램당 스타필로코커스 부하를 한천 플레이트상의 콜로니 형성으로써 수치화하였다. 6.93 (±0.24) log10 CFU g-1인 모의 면역화된 (PBS/보조제) 동물과 비교하여, IsdB 백신접종은 6.25 (±0.46) log10 CFU g-1를 나타냈고 USA300 (LAC) 시험감염으로부터 통계적으로 유의적인 보호 (P=0.2138, 양측 스튜던츠 t-검정)를 발생하지 못했다. 데이터는 3회 독립 분석을 대표한 값이다.
도 9는 PBS, SpA, SpA-D 및 SpA-DKKAA로 처리된 마우스에서의 비교된 농양 형성을 보여준다.
도 10A-10H는 스타필로코커스 농양내에 프로트롬빈, 피브리노겐, 코아귤라제(Coa) 및 폰빌레브란트 인자 결합 단백질 (vWbp)의 편재를 보여준다. 정맥내 접종에 의해 1 x 107 CFU 에스. 아우레우스 뉴만으로 감염된 BALB/c 마우스가 감염 후 5일째 사망하였다. 신장을 제거하고, 파라핀에 고정한 다음, 박편한 후, 마우스 프로트롬빈 (도 10A, 10C), 마우스 피브리노겐/피브린 (도 10B, 10D), 에스. 아우레우스 Coa (도 10E, 10G) 또는 에스. 아우레우스 vWbp (도 10F, 10H)에 특이적인 토끼 항체 (α)를 사용하여 면역화학으로 염색하였다. 제시된 이미지는 3회 신장 샘플을 대표한다. 패널 도 10C, 10D, 10G 및 10H는 백색 가장자리의 표시된 패널 도 10A, 10B, 10E 및 10F에서 한 영역으로부터 확장된 4개의 연속 단편으로 분석된 단일 농양내의 항체 염색을 예시한다.
도 11A-11C. 스타필로코커스 아우레우스 coa 및 vWbp 돌연변이체는 혈액 응고에서 결점을 보여준다. (도 11A) 신호 펩타이드 (S), 프로트롬빈 결합으로부터의 D1 및 D2 도메인, 알려지지 않은 기능의 도메인, vWbp상의 폰빌레브란트 인자(vWF) 결합 부위 및 Coa의 피브리노겐 결합 반복체 (R)을 포함한 coa 및 vWbp의 일차 해독 산물을 예시하는 다이아그램. (도 11B) 에스. 아우레우스 뉴만 (야생형) 또는 coa 유전자가 결실된 (△coa), vWbp 유전자가 결실된 (△vWbp) 또는 두 유전자 모두 결실된 (△coa, △vWbp) 동질유전자형 변이체의 배양 상청액을 Coa (αCoa) 또는 vWbp (αvWbp)에 특이적인 항체로 면역블롯팅하여 검사하였다. 보체 연구를 위해, coa(pcoa) 또는 vWbp(pvWbp)의 야생형 대립유전자를 발현하는 플라스미드를 전기천공에 의해 스타필로코커스 균주내로 도입하고 이어서 면역블롯팅에 의해 분석하였다. (도 11C) 레피루딘-처리된 마우스 혈액을 모의 처리하거나 에스. 아우레우스 뉴만 또는 이의 동질유전자형 코아귤라제 변이체로 감염시키고, 25℃에서 48시간 동안 배양하였다. 튜브를 경사시켜 응고를 평가하였다. 데이터는 4회 독립 측정을 대표하는 것이다.
도 12A-12R는 마우스 혈액 중의 세균 생존 및 에스. 아우레우스 유도된 치명적인 세균감염증에 대한 coa 및 vWbp의 기여를 보여준다. (도 12A) 스타필로코커스 균주 뉴만, △coa, △vWbp 또는 △coa,△vWbp 및 보체화된 변이체를 레피루딘 항응고된 마우스 혈액과 30분간 배양하고 한천 플레이트상의 콜로니 형성에 의해 세균 생존을 평가하였다. 데이터는 3회 독립 시험으로부터 얻었다. (도 12B) 10 마리 마우스 코호트에 1x108 CFU의 에스. 아우레우스 뉴만 (야생형)뿐만 아니라 △coa, △vWbp 또는 △coa,△vWbp를 후안신경총내로 주사하였다. 10일간에 걸쳐 시간 경과에 따른 동물 생존을 기록하였다. B와 유사하게, 마우스에 1x107 CFU의 스타필로코커스 균주 뉴만 (도 12C, E 및 K, M), △vWbp (도 14D, F 및 M, L), △coa (도 14G, I 및 O, Q) 또는 △coa,△vWbp (도 12H, J 및 P, R)을 투여하고, 5일째 (도 12C-J) 또는 15일째 (도 12K-R) 수거한 다음, 신장 조직의 세균 부하 (표 7) 및 조직병리학적 농양 형성을 평가하였다. 모든 동물 데이터는 2회 독립 실험을 대표하는 것이다.
도 13A-13D는 Coa 및 vWbp에 대한 항체가 스타필로코커스 코아귤라제에 의한 혈액 응고를 차단함을 보여준다. (도 13A) His6-Coa 및 His6-vWbp을 이. 콜라이로부터 친화성 크로마토그래피에 의해 정제하고 쿠마시-염색된 SDS-PAGE로 분석하였다. (도 13B) His6-Coa 또는 His6-vWbp에 대해 생성된 토끼 항체를 친화성 정제하고, 정제된 코아귤라제와의 면역 반응성에 대해 ELISA로 분석하였다. 데이터는 3회 독립 실험 측정값의 평균치이다. (도 13C) 레피루딘-처리된 마우스 혈액을 에스. 아우레우스 뉴만으로 감염시키기 전에 PBS (모의), 무관한 항체 (αV10) 또는 Coa(αCoa), vWbp(αvWbp) 또는 이들 두 코아귤라제 모두(αCoa/αvWbp)에 대한 항체로 처리하고 25℃에서 48시간 동안 배양하였다. (도 13D) 레피루딘-처리된 마우스 혈액을 상기한 바와 같이 항체로 처리하였다. 이어서, 혈액 시료를 기능적으로 활성적인 Coa 또는 vWbp와 배양하고 응고 시간을 기록하였다.
도 14A-14F는 스타필로코커스 코아귤라제에 대한 항체의 생물학적 효과를 보여준다. Coa 또는 vWbp와 프로트롬빈 또는 피브리노겐사이의 결합을 방해하는 항체의 표면 플라스몬 공명 측정. 코아귤라제 (Coa)를 프로트롬빈 (도 14A) 또는 피브리노겐 (도 14B)에 첨가했을 때의 반응 차이를 증가 량의 항체 (αCoa - 1:1, 1:2, 1:4, 1:8)존재하에 반응 차이와 비교하였다. vWbp를 프로트롬빈 (도 16A) 또는 피브리노겐 (도 16B)에 첨가했을 때의 반응 차이를 증가량의 항체 (αvWbp - 1:1, 1:2, 1:4, 1:8) 존재하에 반응 차이와 비교하였다. (도 14E, F) 정제된 활성 Coa 또는 vWbp를 사람 프로트롬빈과 1:1 몰비로 배양하였다. 복합체의 효소능을 S-2238 분해율 (과량으로 적용되는 피브리노겐 치환 발색 기질)을 모니터링하여 평가하였다. 이 검정은 3M 과량으로 첨가된 특이적 또는 교차 항체의 존재하에 반복하였고, 데이터는 억제없는 평균 활성%로 정성하였다. 데이터는 3회 독립 시험의 평균치이다.
도 15는 스타필로코커스 세균감염증을 갖는 마우스의 생존에 코아귤라제 특이적 항체의 기여를 보여준다. 감염 24시간 전에 BALB/c 마우스 (n=15)에 정제된 토끼 항체 (5 ㎎ 항체/체중 ㎏)를 복강내로 주사하였다. 이어서, 동물의 후안신경총내로 1x108 CFU 에스. 아우레우스 뉴만을 주사하여 시험감염시키고 생존에 대해 모니터링하였다. 데이터는 2회 독립 실험의 평균치이다.
도 16A-16H 코아귤라제 항체의 수동 전달은 에스. 아우레우스 농양 형성에 대해 방어를 제공한다. 모의 실험용 PBS (도 18A 및 18C) 또는 vWbp(αvWbp, 도 18B 및 18D), Coa(αCoa, 도 18E 및 18G) 또는 이들 두 코아귤라제(αCoa/αvWbp, 도 18F 및 18H)에 대한 정제된 토끼 항체를 BALB/c 마우스 (n=10)의 복강에 주하고 항체 역가를 ELISA로 분석하였다 (표 8). 후안신경총내로 1x107 CFU 에스. 아우레우스 뉴만을 주입하여 수동적으로 면역화된 동물을 감염시켰다. 감염 후 5일째 사망한 동물의 신장을 부검하여 세균 부하 및 농양 형성을 측정하였다. 신장 조직을 파라포름알데하이드로 고정하고, 파라핀에 포매시킨 다음, 박편화하고, 헤마톡실린-에오신으로 염색한 후 광학 현미경으로 조직병리 이미지를 확보하였다. 데이터는 2회 독립 실험의 평균치이다.
도 17A-17H는 코아귤라제로의 면역화가 에스. 아우레우스 농양 형성에 대해 마우스를 방어함을 보여준다. BALB/c 마우스 (n=15)를 0일 및 11일째에 보조제로 현탁화된 50 ㎍ His6-Coa, His6-vWbp, His6-Coa 및 His6-vWbp 또는 PBS (모의)로 면역화하고 항체 역가를 21일째에 ELISA로 분석하였다 (표 8). 21일째에 안와후방 플렉서스내로 1x107 CFU 에스. 아우레우스 뉴만을 주사하여 동물을 시험감염시켰다. 감염 후 5일 경과하여 사망한 동물의 신장을 부검하여 세균 부하 및 농양 형성을 측정하였다. 신장 조직을 파라포름알데하이드로 고정하고, 파라핀에 포매시킨 다음, 박편하고, 헤마톡실린-에오신으로 염색한 후 광학 현미경으로 조직병리 이미지를 확보하였다. 데이터는 2회 독립 실험의 평균치이다.
Claims (117)
- 스타필로코커스 아우레우스(Staphylococcus aureus) 단백질 A (SpA) D 도메인 변이체를 포함하는 분리된 폴리펩타이드로서, 상기 SpA D 도메인 변이체가 서열번호 2의 아미노산 서열과 적어도 70% 동일한 아미노산 서열로 이루어지고, (a) 서열번호 2의 위치 9 및 10에 상응하는 위치에 있는 아미노산들의 리신으로의 치환을 포함하는, Fc 결합을 파괴하는 적어도 2개의 아미노산 치환 및 (b) 서열번호 2의 위치 36 및 37에 상응하는 위치에 있는 아미노산들의 알라닌으로의 치환을 포함하는, VH3 결합을 파괴하는 적어도 2개의 아미노산 치환을 가지는, 분리된 폴리펩타이드.
- 제1항에 있어서, SpA E 도메인, A 도메인, B 도메인 및 C 도메인 분절의 하나 이상의 변이체를 추가로 포함하는, 분리된 폴리펩타이드.
- 제1항에 있어서, 두 개 이상의 D 도메인 분절을 포함하는, 분리된 폴리펩타이드.
- 제1항에 있어서, 제2 항원 분절을 추가로 포함하는, 분리된 폴리펩타이드.
- 제4항에 있어서, 상기 제2 항원 분절이 스타필로코커스 항원 분절인, 분리된 폴리펩타이드.
- 제5항에 있어서, 상기 스타필로코커스 항원 분절이 Emp, EsxA, EsxB, EsaC, Eap, Ebh, EsaB, Coa, vWbp, vWh, Hla, SdrC, SdrD, SdrE, IsdA, IsdB, IsdC, ClfA, ClfB 및 SasF 분절 중의 하나 이상을 포함하는, 분리된 폴리펩타이드.
- 제1항의 분리된 폴리펩타이드를 포함하는, 면역 반응의 자극을 필요로 하는 피검체에서 면역 반응을 자극할 수 있는 펩타이드 조성물.
- 제7항에 있어서, 적어도 제2 스타필로코커스 항원을 추가로 포함하는, 펩타이드 조성물.
- 제1항의 분리된 폴리펩타이드를 포함하고, 상기 폴리펩타이드는 비-독성인, 면역 반응의 자극을 필요로 하는 피검체에서 면역 반응을 자극할 수 있는 면역원성 조성물.
- 제9항에 있어서, Emp, EsxA, EsxB, EsaC, Eap, Ebh, EsaB, Coa, vWbp, vWh, Hla, SdrC, SdrD, SdrE, IsdA, IsdB, IsdC, ClfA, ClfB 및 SasF로 이루어진 그룹으로부터 선택된 하나 이상의 다른 스타필로코커스 항원 또는 이의 면역원성 단편을 추가로 포함하는, 면역원성 조성물.
- 제1항의 분리된 폴리펩타이드 및 약제학적으로 허용되는 부형제를 포함하는, 스타필로코커스 감염의 치료 또는 예방용 백신.
- 제11항에 있어서, 상기 스타필로코커스 감염의 치료 또는 예방용 약제의 제조를 위한, 백신.
- 유효량의 스타필로코커스 아우레우스(Staphylococcus aureus) 단백질 A (SpA) E, D, A, B, C 도메인 변이체를 포함하는 조성물로서,
상기 변이체가, D 도메인 중의 서열번호 2의 위치 9 및 10에 있는 아미노산들의 치환; E 도메인, A 도메인, B 도메인 및 C 도메인 중의 하나 이상에서 서열번호 2의 위치 9 및 10에 상응하는 아미노산들의 치환; D 도메인 중의 서열번호 2의 위치 36 및 37에 있는 아미노산들의 치환; 및 E 도메인, A 도메인, B 도메인 및 C 도메인 중의 하나 이상에서 서열번호 2의 위치 36 및 37에 상응하는 아미노산들의 치환을 포함하고,
이때 상기 위치 9 및 10 또는 9 및 10에 상응하는 위치에서의 아미노산들의 치환은 리신 잔기로의 치환이고, 상기 위치 36 및 37 또는 36 및 37에 상응하는 위치에서의 아미노산들의 치환은 알라닌 잔기로의 치환인, 피검체에서 스타필로코커스 세균에 대한 면역 반응을 유도하기 위한 조성물. - 제13항에 있어서, 제2 스타필로코커스 항원을 추가로 포함하는, 조성물.
- 제14항에 있어서, 상기 제2 스타필로코커스 항원이 Emp, EsxA, EsxB, EsaC, Eap, Ebh, EsaB, Coa, vWbp, vWh, Hla, SdrC, SdrD, SdrE, IsdA, IsdB, IsdC, ClfA, ClfB 및 SasF 중의 하나 이상인, 조성물.
- 숙주 세포로부터 제1항의 폴리펩타이드를 획득하는 단계를 포함하는, 제1항의 폴리펩타이드를 제조하는 방법.
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
Applications Claiming Priority (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US16643209P | 2009-04-03 | 2009-04-03 | |
US61/166,432 | 2009-04-03 | ||
US23795609P | 2009-08-28 | 2009-08-28 | |
US61/237,956 | 2009-08-28 | ||
US28799609P | 2009-12-18 | 2009-12-18 | |
US61/287,996 | 2009-12-18 | ||
PCT/US2010/029959 WO2011005341A2 (en) | 2009-04-03 | 2010-04-05 | Compositions and methods related to protein a (spa) variants |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1020177023725A Division KR20170102039A (ko) | 2009-04-03 | 2010-04-05 | 단백질 A(SpA) 변이체와 관련된 조성물 및 방법 |
Publications (2)
Publication Number | Publication Date |
---|---|
KR20110138397A KR20110138397A (ko) | 2011-12-27 |
KR101773368B1 true KR101773368B1 (ko) | 2017-08-31 |
Family
ID=43429726
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1020177023725A Ceased KR20170102039A (ko) | 2009-04-03 | 2010-04-05 | 단백질 A(SpA) 변이체와 관련된 조성물 및 방법 |
KR1020117026053A Active KR101773368B1 (ko) | 2009-04-03 | 2010-04-05 | 단백질 A(SpA) 변이체와 관련된 조성물 및 방법 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1020177023725A Ceased KR20170102039A (ko) | 2009-04-03 | 2010-04-05 | 단백질 A(SpA) 변이체와 관련된 조성물 및 방법 |
Country Status (21)
Country | Link |
---|---|
US (1) | US9567379B2 (ko) |
EP (3) | EP3002293A1 (ko) |
JP (1) | JP5789250B2 (ko) |
KR (2) | KR20170102039A (ko) |
CN (1) | CN102612523B (ko) |
AU (1) | AU2010271116B2 (ko) |
BR (1) | BRPI1010307B1 (ko) |
CA (1) | CA2757543C (ko) |
CY (1) | CY1123052T1 (ko) |
DK (2) | DK2414387T3 (ko) |
ES (2) | ES2784957T3 (ko) |
HR (2) | HRP20160274T1 (ko) |
HU (2) | HUE057713T2 (ko) |
LT (1) | LT3281947T (ko) |
PL (2) | PL3281947T3 (ko) |
PT (2) | PT2414387E (ko) |
SG (1) | SG174968A1 (ko) |
SI (2) | SI3281947T1 (ko) |
SM (2) | SMT202000246T1 (ko) |
WO (1) | WO2011005341A2 (ko) |
ZA (1) | ZA201107702B (ko) |
Families Citing this family (44)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8840906B2 (en) | 2007-08-31 | 2014-09-23 | The University Of Chicago | Methods and compositions related to immunizing against Staphylococcal lung disease and conditions |
US9181329B2 (en) | 2007-08-31 | 2015-11-10 | The University Of Chicago | Methods and compositions related to immunizing against Staphylococcal lung diseases and conditions |
ES2784957T3 (es) | 2009-04-03 | 2020-10-02 | Univ Chicago | Composiciones y métodos relacionados con variantes de la proteína A (SPA) |
WO2011028492A2 (en) * | 2009-08-24 | 2011-03-10 | The Regents Of The University Of California | Sortase a inhibitors |
CN107188936B (zh) * | 2010-03-24 | 2021-08-10 | 株式会社钟化 | 特异性结合免疫球蛋白的蛋白质以及免疫球蛋白结合性亲和配体 |
JP2013523818A (ja) * | 2010-04-05 | 2013-06-17 | ザ・ユニバーシティー・オブ・シカゴ | 免疫反応のエンハンサーとしてのプロテインA(SpA)抗体に関連する組成物および方法 |
KR20130093084A (ko) | 2010-07-02 | 2013-08-21 | 더 유니버시티 오브 시카고 | 단백질 A(SpA) 변이체와 관련된 조성물 및 방법 |
EP3578205A1 (en) | 2010-08-06 | 2019-12-11 | ModernaTX, Inc. | A pharmaceutical formulation comprising engineered nucleic acids and medical use thereof |
US9095540B2 (en) * | 2010-09-09 | 2015-08-04 | The University Of Chicago | Methods and compositions involving protective staphylococcal antigens |
DE19177059T1 (de) | 2010-10-01 | 2021-10-07 | Modernatx, Inc. | N1-methyl-pseudouracile enthältendes ribonucleinsäuren sowie ihre verwendungen |
AU2012236099A1 (en) | 2011-03-31 | 2013-10-03 | Moderna Therapeutics, Inc. | Delivery and formulation of engineered nucleic acids |
WO2012165544A1 (ja) * | 2011-06-03 | 2012-12-06 | 独立行政法人産業技術総合研究所 | 酸性域での親和性が低下したプロテインa変異型タンパク質及び抗体捕捉剤 |
CA2845259A1 (en) | 2011-08-15 | 2013-02-21 | The University Of Chicago | Compositions and methods related to antibodies to staphylococcal protein a |
US9464124B2 (en) | 2011-09-12 | 2016-10-11 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
SG11201401196WA (en) | 2011-10-03 | 2014-05-29 | Moderna Therapeutics Inc | Modified nucleosides, nucleotides, and nucleic acids, and uses thereof |
JP2015501844A (ja) | 2011-12-16 | 2015-01-19 | モデルナ セラピューティクス インコーポレイテッドModerna Therapeutics,Inc. | 修飾ヌクレオシド、ヌクレオチドおよび核酸組成物 |
WO2013142349A1 (en) * | 2012-03-23 | 2013-09-26 | University Of Chicago | Compositions and methods related to staphylococcal sbi |
US9878056B2 (en) | 2012-04-02 | 2018-01-30 | Modernatx, Inc. | Modified polynucleotides for the production of cosmetic proteins and peptides |
CA2868422A1 (en) | 2012-04-02 | 2013-10-10 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of membrane proteins |
US9283287B2 (en) | 2012-04-02 | 2016-03-15 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of nuclear proteins |
US9572897B2 (en) | 2012-04-02 | 2017-02-21 | Modernatx, Inc. | Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins |
BR112014026861A2 (pt) | 2012-04-26 | 2018-05-15 | Univ Chicago | antígenos de estafilococos coagulase e métodos de seu uso |
US9701738B2 (en) | 2012-04-26 | 2017-07-11 | The University Of Chicago | Compositions and methods related to antibodies that neutralize coagulase activity during Staphylococcus aureus disease |
PT2922554T (pt) | 2012-11-26 | 2022-06-28 | Modernatx Inc | Arn modificado nas porções terminais |
US8980864B2 (en) | 2013-03-15 | 2015-03-17 | Moderna Therapeutics, Inc. | Compositions and methods of altering cholesterol levels |
US20160074497A1 (en) * | 2013-05-03 | 2016-03-17 | The University Of Chicago | Staphylococcus live cell vaccines |
EP3019520B1 (en) | 2013-07-10 | 2019-12-11 | GE Healthcare BioProcess R&D AB | Mutated immunoglobulin-binding polypeptides |
EP3052106A4 (en) | 2013-09-30 | 2017-07-19 | ModernaTX, Inc. | Polynucleotides encoding immune modulating polypeptides |
AU2014329452B2 (en) | 2013-10-03 | 2019-06-20 | Moderna Therapeutics, Inc. | Polynucleotides encoding low density lipoprotein receptor |
CN103540588B (zh) * | 2013-10-08 | 2016-06-08 | 杨波 | 一种基因工程改造的免疫球蛋白-亲和蛋白 |
ES2704860T3 (es) | 2013-12-09 | 2019-03-20 | Olymvax Biopharmaceuticals Inc | Mutante SpA5 de Staphylococcus aureus, composición que comprende el mutante y procedimiento de preparación y utilización del mismo |
KR20160132109A (ko) * | 2014-03-26 | 2016-11-16 | 글락소스미스클라인 바이오로지칼즈 에스.에이. | 돌연변이 스태필로코쿠스 항원 |
BE1022875B1 (fr) * | 2014-03-26 | 2016-09-30 | Glaxosmithkline Biologicals S.A. | Compositions pour une immunisation contre staphylococcus aureus |
WO2016095832A1 (en) * | 2014-12-18 | 2016-06-23 | The University Of Hong Kong | Immunotherapeutic targets against staphylococcus aureus |
CN106188251B (zh) * | 2015-05-06 | 2020-07-31 | 上海迈泰君奥生物技术有限公司 | 一种免疫球蛋白结合蛋白突变体及其用途 |
US11214600B2 (en) | 2016-02-12 | 2022-01-04 | The University Of Chicago | Compositions and methods related to antibodies that neutralize coagulase activity during Staphylococcus aureus disease |
US10738338B2 (en) | 2016-10-18 | 2020-08-11 | The Research Foundation for the State University | Method and composition for biocatalytic protein-oligonucleotide conjugation and protein-oligonucleotide conjugate |
MX2021013833A (es) | 2019-05-14 | 2022-03-17 | Univ Chicago | Metodos y composiciones que comprenden variantes de la proteina a de estafilococos (spa). |
EP3777884A1 (en) | 2019-08-15 | 2021-02-17 | GlaxoSmithKline Biologicals S.A. | Immunogenic composition |
US20220362368A1 (en) * | 2019-10-02 | 2022-11-17 | Janssen Vaccines & Prevention B.V. | Staphylococcus peptides and methods of use |
CN112898387B (zh) * | 2021-03-24 | 2023-04-28 | 成都欧林生物科技股份有限公司 | 一种重组金黄色葡萄球菌疫苗抗原蛋白的纯化方法 |
CN114605508B (zh) * | 2022-05-11 | 2022-07-29 | 北京达成生物科技有限公司 | 能够结合于抗体分子Fc区域的抗体结合蛋白及其应用 |
CN116218751A (zh) * | 2022-10-20 | 2023-06-06 | 昆明医科大学 | 一种金黄色葡萄球菌SdrC蛋白基因敲除的方法 |
KR102650818B1 (ko) * | 2024-01-04 | 2024-03-27 | 한국콜마주식회사 | 황색포도상구균 단백질 a에 대한 항체를 포함하는 피부 진단용 키트 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2002059148A2 (en) * | 2001-01-26 | 2002-08-01 | Intercell Ag | A method for identification, isolation and production of antigens to a specific pathogen |
Family Cites Families (175)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NL154600B (nl) | 1971-02-10 | 1977-09-15 | Organon Nv | Werkwijze voor het aantonen en bepalen van specifiek bindende eiwitten en hun corresponderende bindbare stoffen. |
US3949064A (en) | 1973-10-26 | 1976-04-06 | Baxter Laboratories, Inc. | Method of detecting antigens or antibodies |
GB1499035A (en) | 1975-04-10 | 1978-01-25 | Ts Nii Gematologii I Perelivan | Antistaphylococcus human immune globulin and method of preparing same |
US4174384A (en) | 1975-06-30 | 1979-11-13 | Syva Company | Fluorescence quenching with immunological pairs in immunoassays |
US4367110A (en) | 1979-07-02 | 1983-01-04 | Toppan Printing Co. | Decorative laminate and a manufacturing method therefor |
US4327082A (en) | 1979-07-12 | 1982-04-27 | Adcock-Ingram Laboratories Limited | Mastitis vaccination |
US4372945A (en) | 1979-11-13 | 1983-02-08 | Likhite Vilas V | Antigen compounds |
US4452901A (en) | 1980-03-20 | 1984-06-05 | Ciba-Geigy Corporation | Electrophoretically transferring electropherograms to nitrocellulose sheets for immuno-assays |
US4338298A (en) | 1980-04-04 | 1982-07-06 | Endowment And Research Foundation At Montana State University | Vaccine for passive immunization against enteric colibacillosis and method of use |
US4554101A (en) | 1981-01-09 | 1985-11-19 | New York Blood Center, Inc. | Identification and preparation of epitopes on antigens and allergens on the basis of hydrophilicity |
IL61904A (en) | 1981-01-13 | 1985-07-31 | Yeda Res & Dev | Synthetic vaccine against influenza virus infections comprising a synthetic peptide and process for producing same |
US4356170A (en) | 1981-05-27 | 1982-10-26 | Canadian Patents & Development Ltd. | Immunogenic polysaccharide-protein conjugates |
US4596792A (en) | 1981-09-04 | 1986-06-24 | The Regents Of The University Of California | Safe vaccine for hepatitis containing polymerized serum albumin |
NL8200523A (nl) | 1982-02-11 | 1983-09-01 | Univ Leiden | Werkwijze voor het in vitro transformeren van planteprotoplasten met plasmide-dna. |
US4748018A (en) | 1984-02-07 | 1988-05-31 | Stolle Research & Development Corp. | Method of passive immunization of mammals using avian antibody |
JPS5938877A (ja) | 1982-08-30 | 1984-03-02 | Musashi Eng Kk | 紙葉判別方法 |
US5151350A (en) | 1982-10-27 | 1992-09-29 | Repligen Corporation | Cloned genes encoding recombinant protein a |
US4599230A (en) | 1984-03-09 | 1986-07-08 | Scripps Clinic And Research Foundation | Synthetic hepatitis B virus vaccine including both T cell and B cell determinants |
US4599231A (en) | 1984-03-09 | 1986-07-08 | Scripps Clinic And Research Foundation | Synthetic hepatitis B virus vaccine including both T cell and B cell determinants |
US4879236A (en) | 1984-05-16 | 1989-11-07 | The Texas A&M University System | Method for producing a recombinant baculovirus expression vector |
US5189015A (en) | 1984-05-30 | 1993-02-23 | Alfa-Laval Agri International Ab | Method for prophylactic treatment of the colonization of a Staphylococcus aureus bacterial strain by bacterial cell surface protein with fibronectin and fibrinogen binding ability |
US5310687A (en) | 1984-10-31 | 1994-05-10 | Igen, Inc. | Luminescent metal chelate labels and means for detection |
US5221605A (en) | 1984-10-31 | 1993-06-22 | Igen, Inc. | Luminescent metal chelate labels and means for detection |
US5238808A (en) | 1984-10-31 | 1993-08-24 | Igen, Inc. | Luminescent metal chelate labels and means for detection |
US4608251A (en) | 1984-11-09 | 1986-08-26 | Pitman-Moore, Inc. | LHRH analogues useful in stimulating anti-LHRH antibodies and vaccines containing such analogues |
US4683202A (en) | 1985-03-28 | 1987-07-28 | Cetus Corporation | Process for amplifying nucleic acid sequences |
US4683195A (en) | 1986-01-30 | 1987-07-28 | Cetus Corporation | Process for amplifying, detecting, and/or-cloning nucleic acid sequences |
US4601903A (en) | 1985-05-01 | 1986-07-22 | The United States Of America As Represented By The Department Of Health And Human Services | Vaccine against Neisseria meningitidis Group B serotype 2 invasive disease |
US4690915A (en) | 1985-08-08 | 1987-09-01 | The United States Of America As Represented By The Department Of Health And Human Services | Adoptive immunotherapy as a treatment modality in humans |
US4800159A (en) | 1986-02-07 | 1989-01-24 | Cetus Corporation | Process for amplifying, detecting, and/or cloning nucleic acid sequences |
US5084269A (en) | 1986-11-06 | 1992-01-28 | Kullenberg Fred W | Adjuvant for dose treatment with antigens |
AU622104B2 (en) | 1987-03-11 | 1992-04-02 | Sangtec Molecular Diagnostics Ab | Method of assaying of nucleic acids, a reagent combination and kit therefore |
US5320951A (en) | 1987-06-01 | 1994-06-14 | Hoeoek Magnus | Fibronectin binding protein as well as its preparation |
FR2619122B1 (fr) | 1987-08-03 | 1990-03-09 | Pasteur Institut | Procede d'obtention de polyosides capsulaires de staphylocoques, polyosides obtenus, applications de ces polyosides et souches pour la mise en oeuvre du procede |
US4952500A (en) | 1988-02-01 | 1990-08-28 | University Of Georgia Research Foundation, Inc. | Cloning systems for Rhodococcus and related bacteria |
US5258494A (en) * | 1988-04-08 | 1993-11-02 | Stryker Corporation | Osteogenic proteins |
US5858652A (en) | 1988-08-30 | 1999-01-12 | Abbott Laboratories | Detection and amplification of target nucleic acid sequences |
US5703055A (en) | 1989-03-21 | 1997-12-30 | Wisconsin Alumni Research Foundation | Generation of antibodies through lipid mediated DNA delivery |
SE8901687D0 (sv) | 1989-05-11 | 1989-05-11 | Alfa Laval Agri Int | Fibronectin binding protein as well as its preparation |
US5302523A (en) | 1989-06-21 | 1994-04-12 | Zeneca Limited | Transformation of plant cells |
US5550318A (en) | 1990-04-17 | 1996-08-27 | Dekalb Genetics Corporation | Methods and compositions for the production of stably transformed, fertile monocot plants and cells thereof |
US7705215B1 (en) | 1990-04-17 | 2010-04-27 | Dekalb Genetics Corporation | Methods and compositions for the production of stably transformed, fertile monocot plants and cells thereof |
US5322783A (en) | 1989-10-17 | 1994-06-21 | Pioneer Hi-Bred International, Inc. | Soybean transformation by microparticle bombardment |
US5484956A (en) | 1990-01-22 | 1996-01-16 | Dekalb Genetics Corporation | Fertile transgenic Zea mays plant comprising heterologous DNA encoding Bacillus thuringiensis endotoxin |
SE466259B (sv) | 1990-05-31 | 1992-01-20 | Arne Forsgren | Protein d - ett igd-bindande protein fraan haemophilus influenzae, samt anvaendning av detta foer analys, vacciner och uppreningsaendamaal |
US5384253A (en) | 1990-12-28 | 1995-01-24 | Dekalb Genetics Corporation | Genetic transformation of maize cells by electroporation of cells pretreated with pectin degrading enzymes |
CA2059692C (en) | 1991-01-28 | 2004-11-16 | Peter J. Kniskern | Pneumoccoccal polysaccharide conjugate vaccine |
CA2059693C (en) | 1991-01-28 | 2003-08-19 | Peter J. Kniskern | Polysaccharide antigens from streptococcus pneumoniae |
US5199942A (en) | 1991-06-07 | 1993-04-06 | Immunex Corporation | Method for improving autologous transplantation |
WO1993004169A1 (en) | 1991-08-20 | 1993-03-04 | Genpharm International, Inc. | Gene targeting in animal cells using isogenic dna constructs |
US5610042A (en) | 1991-10-07 | 1997-03-11 | Ciba-Geigy Corporation | Methods for stable transformation of wheat |
US5620896A (en) | 1992-03-23 | 1997-04-15 | University Of Massachusetts Medical Center | DNA vaccines against rotavirus infections |
WO1993018784A1 (en) | 1992-03-26 | 1993-09-30 | Microcarb, Inc. | Monospecific polyclonal antibodies to shiga-like toxins |
DK0604662T3 (da) | 1992-07-07 | 2008-10-20 | Japan Tobacco Inc | Fremgangsmåde til transformering af monocotyledon |
US5702932A (en) | 1992-07-20 | 1997-12-30 | University Of Florida | Microinjection methods to transform arthropods with exogenous DNA |
AU670316B2 (en) | 1992-07-27 | 1996-07-11 | Pioneer Hi-Bred International, Inc. | An improved method of (agrobacterium)-mediated transformation of cultured soybean cells |
DE4228457A1 (de) | 1992-08-27 | 1994-04-28 | Beiersdorf Ag | Herstellung von heterodimerem PDGF-AB mit Hilfe eines bicistronischen Vektorsystems in Säugerzellen |
CA2124210A1 (en) | 1992-09-21 | 1994-03-31 | Maria K. Boden | Fibrinogen binding protein |
GB9222888D0 (en) | 1992-10-30 | 1992-12-16 | British Tech Group | Tomography |
US5846709A (en) | 1993-06-15 | 1998-12-08 | Imclone Systems Incorporated | Chemical process for amplifying and detecting nucleic acid sequences |
FR2708288B1 (fr) | 1993-07-26 | 1995-09-01 | Bio Merieux | Procédé d'amplification d'acides nucléiques par transcription utilisant le déplacement, réactifs et nécessaire pour la mise en Óoeuvre de ce procédé. |
DE69433341T2 (de) | 1993-09-22 | 2004-04-15 | Henry M. Jackson Foundation For The Advancement Of Military Medicine | Verfahren zur aktivierung von löslichem kohlenhydraten durch verwendung von neuen cyanylierungsreagenzien, zur herstellung von immunogenischen konstrukten |
US5928905A (en) | 1995-04-18 | 1999-07-27 | Glaxo Group Limited | End-complementary polymerase reaction |
US5648240A (en) | 1994-05-24 | 1997-07-15 | Texas A&M University | MHC II analog from Staphylococcus aureus |
NZ287118A (en) | 1994-05-28 | 1999-01-28 | Tepnel Medical Ltd | Method of detecting and amplifying oligonucleotides |
US5656610A (en) | 1994-06-21 | 1997-08-12 | University Of Southern California | Producing a protein in a mammal by injection of a DNA-sequence into the tongue |
US5942391A (en) | 1994-06-22 | 1999-08-24 | Mount Sinai School Of Medicine | Nucleic acid amplification method: ramification-extension amplification method (RAM) |
FR2722208B1 (fr) | 1994-07-05 | 1996-10-04 | Inst Nat Sante Rech Med | Nouveau site interne d'entree des ribosomes, vecteur le contenant et utilisation therapeutique |
US6008341A (en) | 1994-08-22 | 1999-12-28 | The Provost, Fellows And Scholars Of The College Of The Holy And Undivided Trinity Of Queen Elizabeth Near Dublin | S. aureus fibrinogen binding protein gene |
US5871986A (en) | 1994-09-23 | 1999-02-16 | The General Hospital Corporation | Use of a baculovirus to express and exogenous gene in a mammalian cell |
US5736524A (en) | 1994-11-14 | 1998-04-07 | Merck & Co.,. Inc. | Polynucleotide tuberculosis vaccine |
US5935825A (en) | 1994-11-18 | 1999-08-10 | Shimadzu Corporation | Process and reagent for amplifying nucleic acid sequences |
US5548066A (en) | 1994-12-02 | 1996-08-20 | Central Biomedia, Inc. | Failure of passive transfer immune serum and method of making same |
US6770278B1 (en) | 1994-12-02 | 2004-08-03 | Central Biomedia, Inc. | Methods of making and using immunoglobulin (Ig) compositions |
US5843650A (en) | 1995-05-01 | 1998-12-01 | Segev; David | Nucleic acid detection and amplification by chemical linkage of oligonucleotides |
WO1997014800A1 (en) | 1995-10-16 | 1997-04-24 | Smithkline Beecham Plc | Novel saliva binding protein |
US5780448A (en) | 1995-11-07 | 1998-07-14 | Ottawa Civic Hospital Loeb Research | DNA-based vaccination of fish |
US6833253B2 (en) | 1996-01-05 | 2004-12-21 | Human Genome Sciences, Inc. | Staphylococcus aureus polynucleotides and polypeptides |
US6737248B2 (en) | 1996-01-05 | 2004-05-18 | Human Genome Sciences, Inc. | Staphylococcus aureus polynucleotides and sequences |
US5612473A (en) | 1996-01-16 | 1997-03-18 | Gull Laboratories | Methods, kits and solutions for preparing sample material for nucleic acid amplification |
FR2746398B1 (fr) | 1996-03-21 | 1998-04-30 | Bio Merieux | Anticorps specifique de staphylococcus aureaus, et utilisations |
US5928906A (en) | 1996-05-09 | 1999-07-27 | Sequenom, Inc. | Process for direct sequencing during template amplification |
WO1997043314A2 (en) | 1996-05-16 | 1997-11-20 | The Texas A & M University System | Collagen binding protein compositions and methods of use |
US6013763A (en) | 1996-06-04 | 2000-01-11 | Genentech, Inc. | Peptide variants of protein A |
US5939291A (en) | 1996-06-14 | 1999-08-17 | Sarnoff Corporation | Microfluidic method for nucleic acid amplification |
US5945100A (en) | 1996-07-31 | 1999-08-31 | Fbp Corporation | Tumor delivery vehicles |
US6294177B1 (en) | 1996-09-11 | 2001-09-25 | Nabi | Staphylococcus aureus antigen-containing whole cell vaccine |
US5849546A (en) | 1996-09-13 | 1998-12-15 | Epicentre Technologies Corporation | Methods for using mutant RNA polymerases with reduced discrimination between non-canonical and canonical nucleoside triphosphates |
US5981274A (en) | 1996-09-18 | 1999-11-09 | Tyrrell; D. Lorne J. | Recombinant hepatitis virus vectors |
WO1998017820A1 (en) | 1996-10-23 | 1998-04-30 | American Home Products Corporation | Vaccines |
US5849497A (en) | 1997-04-03 | 1998-12-15 | The Research Foundation Of State University Of New York | Specific inhibition of the polymerase chain reaction using a non-extendable oligonucleotide blocker |
US6610293B1 (en) | 1997-06-16 | 2003-08-26 | The Henry M. Jackson Foundation For The Advancement Of Military Medicine | Opsonic and protective monoclonal and chimeric antibodies specific for lipoteichoic acid of gram positive bacteria |
US5866366A (en) | 1997-07-01 | 1999-02-02 | Smithkline Beecham Corporation | gidB |
US5916776A (en) | 1997-08-27 | 1999-06-29 | Sarnoff Corporation | Amplification method for a polynucleotide |
US6756361B1 (en) | 1997-10-14 | 2004-06-29 | Nabi | Enterococcus antigens and vaccines |
US5994624A (en) | 1997-10-20 | 1999-11-30 | Cotton Incorporated | In planta method for the production of transgenic plants |
US5932451A (en) | 1997-11-19 | 1999-08-03 | Incyte Pharmaceuticals, Inc. | Method for unbiased mRNA amplification |
US6680195B1 (en) | 1997-11-26 | 2004-01-20 | Inhibitex, Inc. | Extracellular matrix-binding proteins from staphylococcus aureus |
JP4486748B2 (ja) | 1997-11-26 | 2010-06-23 | インヒビテツクス,インコーポレイテツド | 黄色ブドウ球菌由来の細胞外マトリックス結合タンパク質 |
DE69941454D1 (de) | 1998-07-10 | 2009-11-05 | U S Medical Res Inst Of Infect | Impfstoff gegen staphylokokken-vergiftung |
US6692739B1 (en) | 1998-08-31 | 2004-02-17 | Inhibitex, Inc. | Staphylococcal immunotherapeutics via donor selection and donor stimulation |
CA2777661C (en) | 1998-08-31 | 2014-10-21 | Inhibitex, Inc. | Multicomponent vaccines |
AU762978B2 (en) | 1998-08-31 | 2003-07-10 | Inhibitex, Inc. | Staphylococcal immunotherapeutics via donor selection and donor stimulation |
CA2341018C (en) | 1998-08-31 | 2012-07-31 | The Provost Fellows And Scholars Of The College Of The Holy And Undivided Trinity Of Queen Elizabeth Near Dublin | Polypeptides and polynucleotides from coagulase-negative staphylococci |
US6703025B1 (en) | 1998-08-31 | 2004-03-09 | Inhibitex, Inc. | Multicomponent vaccines |
AU6131999A (en) | 1998-09-01 | 2000-03-21 | Human Genome Sciences, Inc. | (staphylococcus aureus) genes and polypeptides |
DE69940371D1 (de) | 1998-09-14 | 2009-03-19 | Nabi Biopharmaceuticals Rockvi | Beta-glucan enthaltende zusammenstellungen und spezifische immunoglobuline |
AU769539B2 (en) | 1999-01-29 | 2004-01-29 | Zoetis Services Llc | Adjuvants for use in vaccines |
US6936258B1 (en) | 1999-03-19 | 2005-08-30 | Nabi Biopharmaceuticals | Staphylococcus antigen and vaccine |
WO2000064925A1 (en) | 1999-04-28 | 2000-11-02 | The Provost Fellows And Scholars Of The College Of The Holy And Undivided Trinity Of Queen Elizabeth Near Dublin | Method of inhibiting leukocyte adhesion to fibrinogen |
CA2373221A1 (en) | 1999-05-03 | 2000-11-30 | Yashwant M. Deo | Human antibodies to staphylococcus aureus |
AU777005B2 (en) | 1999-05-15 | 2004-09-30 | University Of California, San Diego | Protein A based binding domains with desirable activities |
WO2001034809A2 (en) | 1999-11-09 | 2001-05-17 | Glaxo Group Limited | Staphylococcus epidermidis nucleic acids and proteins |
AU1813701A (en) | 1999-12-03 | 2001-06-12 | Celltech Chiroscience Limited | Interleukin-1 muteins useful as vaccine adjuvants |
US6651655B1 (en) | 2000-01-18 | 2003-11-25 | Quadrant Technologies Limited | Inhaled vaccines |
SE0000514D0 (sv) | 2000-02-17 | 2000-02-17 | Biostapro Ab | A 52 kDa protein from coagulase negative staphylococci and fragments |
EP1267930A4 (en) | 2000-03-17 | 2005-01-19 | Inhibitex Inc | CROSS-REACTION DISPLACEMENT ANTIBODIES FROM COLLAGEN BINDING PROTEINS AND METHOD OF IDENTIFICATION AND USE |
AU2001249345A1 (en) | 2000-03-21 | 2001-10-03 | Elitra Pharmaceuticals, Inc. | Identification of essential genes in prokaryotes |
GB0014907D0 (en) | 2000-06-20 | 2000-08-09 | Univ Sheffield | Antigenic polypeptides |
SE0003573D0 (sv) * | 2000-10-04 | 2000-10-04 | Bengt Guss | Method and means for producing novel von Willebrand factor binding proteins and their use in biotechnology |
CA2428103C (en) | 2000-11-07 | 2015-06-09 | Immunovaccine Technologies Inc. | Vaccines with enhanced immune response and methods for their preparation |
WO2002074324A1 (en) | 2001-03-15 | 2002-09-26 | The Texas A & M University System | Collagen-binding adhesin from staphylococcus epidermidis and method of use |
GB0107661D0 (en) * | 2001-03-27 | 2001-05-16 | Chiron Spa | Staphylococcus aureus |
US6790448B2 (en) | 2001-05-08 | 2004-09-14 | The Texas A&M University System University | Surface proteins from gram-positive bacteria having highly conserved motifs and antibodies that recognize them |
CN100359327C (zh) | 2001-06-15 | 2008-01-02 | 英希比泰克斯公司 | 识别凝血酶阴性的葡萄球菌和金黄色葡萄球菌的表面蛋白的交叉反应性单克隆抗体和多克隆抗体 |
CA2351018A1 (en) | 2001-07-09 | 2003-01-09 | Universite De Sherbrooke | Dna vaccine against staphylococcus aureus |
EP1412379B1 (en) | 2001-08-02 | 2012-01-25 | The University Of Sheffield | Vaccine |
US20030113350A1 (en) | 2001-09-19 | 2003-06-19 | Fattom Ali I. | Glycoconjugate vaccines for use in immune-compromised populations |
US7115264B2 (en) | 2001-11-05 | 2006-10-03 | Inhibitex | Monoclonal antibodies to the fibronectin binding protein and method of use in treating or preventing infections |
WO2003041726A1 (en) | 2001-11-16 | 2003-05-22 | Biostapro Ab | Use of an extracellular adherence protein for the manufacture of an anti-inflammatory drug |
ATE419005T1 (de) | 2001-12-11 | 2009-01-15 | Merck & Co Inc | Staphylococcus aureus exopolysaccharid und verfahren |
JP2005536185A (ja) | 2002-03-05 | 2005-12-02 | インヒビテックス インコーポレーテッド | コアグラーゼ陰性ブドウ球菌タンパク質を認識するモノクローナルおよびポリクローナル抗体 |
US7736652B2 (en) | 2002-03-21 | 2010-06-15 | The Regents Of The University Of California | Antibody fusion proteins: effective adjuvants of protein vaccination |
US6984381B2 (en) | 2002-07-05 | 2006-01-10 | The United States Of America As Represented By The Secretary Of Agriculture | Vaccine for the prevention of bacterial infection of the bovine mammary gland |
JP4686188B2 (ja) | 2002-09-13 | 2011-05-18 | ザ テキサス エイ アンド エム ユニバースティ システム | グラム陽性菌由来の表面固定化タンパク質を同定するためのバイオインフォマティクス法及びそれによって得られるタンパク質 |
EP1545617A1 (en) | 2002-10-03 | 2005-06-29 | Intercell AG | Use of molecules which interact with the haptoglobin receptor ligand binding |
AU2003290867A1 (en) | 2002-11-12 | 2004-06-03 | The Brigham And Women's Hospital, Inc. | Methods and products for treating staphylococcal infections |
JP5814494B2 (ja) | 2002-11-12 | 2015-11-17 | ザ ブリガム アンド ウィメンズ ホスピタル インコーポレイテッドThe Brigham and Women’s Hospital, Inc. | Staphylococcus感染に対する多糖類ワクチン |
AU2003284643A1 (en) * | 2002-11-22 | 2004-06-18 | Daiichi Pure Chemicals Co., Ltd. | Method of examining staphylococcus aureus |
EP1611155A2 (en) | 2003-03-28 | 2006-01-04 | Elusys Therapeutics, Inc. | Method and compositions for conversion of antibody activity |
US20070053925A1 (en) | 2003-04-16 | 2007-03-08 | Eric Brown | Staphylococcus aureus efb protein and c3 binding region which inhibit complement activation |
US20060188515A1 (en) | 2003-07-24 | 2006-08-24 | Anderson Annaliesa S | Polypeptides for inducing a protective immune response against staphylococcus aureus |
WO2005009379A2 (en) | 2003-07-24 | 2005-02-03 | Merck & Co., Inc. | Polypeptides for inducing a protective immune response against staphylococcus aureus |
US20080160089A1 (en) * | 2003-10-14 | 2008-07-03 | Medivas, Llc | Vaccine delivery compositions and methods of use |
JP2007528217A (ja) | 2004-02-18 | 2007-10-11 | メルク エンド カムパニー インコーポレーテッド | スタヒロコッカス・アウレウスに対する防御免疫応答を誘導するためのポリペプチド |
EP1791560A4 (en) | 2004-09-17 | 2009-01-14 | Merck & Co Inc | POLYPEPTIDES FOR INDUCING AN IMMUNE RESPONSE OF PROTECTION DIRECTED AGAINST STAPHYLOCOCCUS AUREUS |
WO2006032472A2 (en) | 2004-09-22 | 2006-03-30 | Glaxosmithkline Biologicals S.A. | Immunogenic composition for use in vaccination against staphylococcei |
KR20070085457A (ko) | 2004-10-25 | 2007-08-27 | 더 유니버시티 오브 웨스턴 온타리오 | 스태필로코쿠스 아우레우스의 철에 의해 조절되는 표면결정인자 IsdA, IsdB, 및 IsdC 기재 백신,조성물 및 방법 |
CA2585849A1 (en) | 2004-10-29 | 2006-05-11 | Elusys Therapeutics, Inc. | Use of cr1-binding molecules in clearance and induction of immune responses |
US20060134141A1 (en) | 2004-12-14 | 2006-06-22 | Nabi Biopharmaceuticals | Glycoconjugate vaccines containing peptidoglycan |
BRPI0606481A2 (pt) | 2005-01-20 | 2009-06-30 | Isconova Ab | composição de vacina compreendendo uma proteìna de ligação a fibronectina ou um peptìdeo de ligação a fibronectina |
US20060228368A1 (en) | 2005-04-07 | 2006-10-12 | Nabi Biopharmaceuticals | Method of protecting against staphylococcal infection |
US8398991B2 (en) | 2005-06-22 | 2013-03-19 | Institut Pasteur | Modified ESAT-6 molecules and improved vaccine strains of Mycobacterium bovis BCG |
GB0526038D0 (en) | 2005-12-21 | 2006-02-01 | Glaxosmithkline Biolog Sa | Immunogenic composition |
CA2637598A1 (en) * | 2006-01-18 | 2007-02-14 | University Of Chicago | Compositions and methods related to staphylococcal bacterium proteins |
CN101375161A (zh) | 2006-01-27 | 2009-02-25 | 默克公司 | 靶定金黄色葡萄球菌ORF0657n的抗原结合蛋白 |
WO2007095057A2 (en) | 2006-02-10 | 2007-08-23 | Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services | Use of eap protein for treating and preventing autoimmune neuroinflammatory diseases |
AU2007221321B2 (en) | 2006-02-22 | 2012-06-28 | The Texas A & M University System | Antibodies recognizing a highly expressed putative antigen of CA-MRSA and methods of use |
EA020459B1 (ru) | 2006-03-30 | 2014-11-28 | Глаксосмитклайн Байолоджикалс С.А. | Иммуногенная композиция |
AR060187A1 (es) | 2006-03-30 | 2008-05-28 | Glaxosmithkline Biolog Sa | Composicion inmunogenica |
JP2009539979A (ja) | 2006-06-12 | 2009-11-19 | ナビ バイオファーマシューティカルズ | ブドウ球菌感染症を治療および予防するための、α毒素の使用 |
CA2667788A1 (en) | 2006-10-30 | 2008-12-18 | The University Of Western Ontario | Staphylococcus aureus specific anti-infectives |
WO2008140487A2 (en) | 2006-11-14 | 2008-11-20 | Elusys Therapeutics, Inc. | Improved staphylococcal protein a mono- and bispecific antibodies and methods of their use |
US7488807B2 (en) | 2006-11-22 | 2009-02-10 | 3M Innovative Properties Company | Antibody with protein A selectivity |
US20100047252A1 (en) | 2006-11-22 | 2010-02-25 | 3M Innovative Properties Company | Antibody with protein a selectivity |
GB0700136D0 (en) | 2007-01-04 | 2007-02-14 | Glaxosmithkline Biolog Sa | Process for manufacturing vaccines |
US20100166772A1 (en) | 2007-05-31 | 2010-07-01 | Anderson Annaliesa S | ANTIGEN-BINDING PROTEINS TARGETING S. AUREUS ORF0657n |
CN102089005A (zh) | 2008-05-12 | 2011-06-08 | 斯特罗克斯生物制药有限责任公司 | 金黄色葡萄球菌特异性抗体制剂 |
US8592555B2 (en) | 2008-08-11 | 2013-11-26 | Emd Millipore Corporation | Immunoglobulin-binding proteins with improved specificity |
MX2011006870A (es) | 2008-12-23 | 2011-07-19 | Genentech Inc | Variantes de inmunoglobulina con union alterada a proteina a. |
ES2784957T3 (es) | 2009-04-03 | 2020-10-02 | Univ Chicago | Composiciones y métodos relacionados con variantes de la proteína A (SPA) |
SG10201406520YA (en) | 2009-06-22 | 2014-11-27 | Wyeth Llc | Immunogenic compositions of staphylococcus aureus antigens |
FR2957821B1 (fr) | 2010-03-24 | 2014-08-29 | Inst Francais Du Petrole | Nouvelle zone de regeneration du catalyseur divisee en secteurs pour unites catalytiques regeneratives |
JP2013523818A (ja) | 2010-04-05 | 2013-06-17 | ザ・ユニバーシティー・オブ・シカゴ | 免疫反応のエンハンサーとしてのプロテインA(SpA)抗体に関連する組成物および方法 |
KR20130093084A (ko) * | 2010-07-02 | 2013-08-21 | 더 유니버시티 오브 시카고 | 단백질 A(SpA) 변이체와 관련된 조성물 및 방법 |
-
2010
- 2010-04-05 ES ES17193256T patent/ES2784957T3/es active Active
- 2010-04-05 JP JP2012503769A patent/JP5789250B2/ja active Active
- 2010-04-05 KR KR1020177023725A patent/KR20170102039A/ko not_active Ceased
- 2010-04-05 SG SG2011070802A patent/SG174968A1/en unknown
- 2010-04-05 HU HUE17193256A patent/HUE057713T2/hu unknown
- 2010-04-05 HR HRP20160274TT patent/HRP20160274T1/hr unknown
- 2010-04-05 SI SI201032006T patent/SI3281947T1/sl unknown
- 2010-04-05 EP EP15190262.4A patent/EP3002293A1/en not_active Withdrawn
- 2010-04-05 PT PT107974685T patent/PT2414387E/pt unknown
- 2010-04-05 PL PL17193256T patent/PL3281947T3/pl unknown
- 2010-04-05 AU AU2010271116A patent/AU2010271116B2/en active Active
- 2010-04-05 EP EP10797468.5A patent/EP2414387B1/en active Active
- 2010-04-05 EP EP17193256.9A patent/EP3281947B1/en active Active
- 2010-04-05 WO PCT/US2010/029959 patent/WO2011005341A2/en active Application Filing
- 2010-04-05 US US13/260,878 patent/US9567379B2/en active Active
- 2010-04-05 KR KR1020117026053A patent/KR101773368B1/ko active Active
- 2010-04-05 CA CA2757543A patent/CA2757543C/en active Active
- 2010-04-05 CN CN201080024448.7A patent/CN102612523B/zh active Active
- 2010-04-05 SI SI201031085T patent/SI2414387T1/sl unknown
- 2010-04-05 SM SM20200246T patent/SMT202000246T1/it unknown
- 2010-04-05 HU HUE10797468A patent/HUE026855T2/en unknown
- 2010-04-05 ES ES10797468.5T patent/ES2563646T3/es active Active
- 2010-04-05 PL PL10797468T patent/PL2414387T3/pl unknown
- 2010-04-05 LT LTEP17193256.9T patent/LT3281947T/lt unknown
- 2010-04-05 DK DK10797468.5T patent/DK2414387T3/en active
- 2010-04-05 PT PT171932569T patent/PT3281947T/pt unknown
- 2010-04-05 BR BRPI1010307-4A patent/BRPI1010307B1/pt active IP Right Grant
- 2010-04-05 DK DK17193256.9T patent/DK3281947T3/da active
-
2011
- 2011-10-20 ZA ZA2011/07702A patent/ZA201107702B/en unknown
-
2016
- 2016-02-09 SM SM201600033T patent/SMT201600033B/it unknown
-
2020
- 2020-05-06 HR HRP20200727TT patent/HRP20200727T1/hr unknown
- 2020-05-12 CY CY20201100438T patent/CY1123052T1/el unknown
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2002059148A2 (en) * | 2001-01-26 | 2002-08-01 | Intercell Ag | A method for identification, isolation and production of antigens to a specific pathogen |
Non-Patent Citations (2)
Title |
---|
Maghnus ?Seaghdha 등. FEBS. Vol. 273, No. 21, 페이지 4831-4841 (2006.) |
Martin Mempel 등. J Invest Dermatol. Vol. 111, No. 3, 페이지 452-456 (1998.)* |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
KR101773368B1 (ko) | 단백질 A(SpA) 변이체와 관련된 조성물 및 방법 | |
US20240190927A1 (en) | COMPOSITIONS AND METHODS RELATED TO PROTEIN A (SpA) VARIANTS | |
JP6042574B2 (ja) | 免疫反応のエンハンサーとしてのプロテインA(SpA)抗体に関連する組成物および方法 | |
JP5793194B2 (ja) | 感染防御ブドウ球菌抗原が関与する方法および組成物 | |
JP2018121640A (ja) | ブドウ球菌コアグラーゼ抗原およびその使用方法 | |
JP7643730B2 (ja) | ブドウ球菌(Staphylococcus)プロテインA(SpA)変種を含む方法および組成物 | |
AU2015202158B2 (en) | Compositions and methods related to protein a (spa) variants | |
CN103314008B (zh) | 涉及保护性葡萄球菌抗原的方法和组合物 | |
HK1162533B (en) | Compositions and methods related to protein a (spa) variants |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PA0105 | International application |
Patent event date: 20111101 Patent event code: PA01051R01D Comment text: International Patent Application |
|
PG1501 | Laying open of application | ||
A201 | Request for examination | ||
PA0201 | Request for examination |
Patent event code: PA02012R01D Patent event date: 20150225 Comment text: Request for Examination of Application |
|
E902 | Notification of reason for refusal | ||
PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 20151218 Patent event code: PE09021S01D |
|
E902 | Notification of reason for refusal | ||
PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 20160719 Patent event code: PE09021S01D |
|
E902 | Notification of reason for refusal | ||
PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 20170125 Patent event code: PE09021S01D |
|
E701 | Decision to grant or registration of patent right | ||
PE0701 | Decision of registration |
Patent event code: PE07011S01D Comment text: Decision to Grant Registration Patent event date: 20170525 |
|
A107 | Divisional application of patent | ||
PA0104 | Divisional application for international application |
Comment text: Divisional Application for International Patent Patent event code: PA01041R01D Patent event date: 20170824 |
|
GRNT | Written decision to grant | ||
PR0701 | Registration of establishment |
Comment text: Registration of Establishment Patent event date: 20170825 Patent event code: PR07011E01D |
|
PR1002 | Payment of registration fee |
Payment date: 20170828 End annual number: 3 Start annual number: 1 |
|
PG1601 | Publication of registration | ||
PR1001 | Payment of annual fee |
Payment date: 20200730 Start annual number: 4 End annual number: 4 |
|
PR1001 | Payment of annual fee |
Payment date: 20210728 Start annual number: 5 End annual number: 5 |
|
PR1001 | Payment of annual fee |
Payment date: 20220718 Start annual number: 6 End annual number: 6 |
|
PR1001 | Payment of annual fee |
Payment date: 20230718 Start annual number: 7 End annual number: 7 |
|
PR1001 | Payment of annual fee |
Payment date: 20240722 Start annual number: 8 End annual number: 8 |