CA3125293A1 - Production of recombinant vaccine in e. coli by enzymatic conjugation - Google Patents
Production of recombinant vaccine in e. coli by enzymatic conjugation Download PDFInfo
- Publication number
- CA3125293A1 CA3125293A1 CA3125293A CA3125293A CA3125293A1 CA 3125293 A1 CA3125293 A1 CA 3125293A1 CA 3125293 A CA3125293 A CA 3125293A CA 3125293 A CA3125293 A CA 3125293A CA 3125293 A1 CA3125293 A1 CA 3125293A1
- Authority
- CA
- Canada
- Prior art keywords
- gram
- negative bacterium
- pneumoniae
- gene
- protein
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 53
- 241000588724 Escherichia coli Species 0.000 title claims description 51
- 230000021615 conjugation Effects 0.000 title description 11
- 230000002255 enzymatic effect Effects 0.000 title description 5
- 108010008038 Synthetic Vaccines Proteins 0.000 title description 2
- 229940124551 recombinant vaccine Drugs 0.000 title description 2
- 238000000034 method Methods 0.000 claims abstract description 32
- 150000004676 glycans Chemical class 0.000 claims description 155
- 229920001282 polysaccharide Polymers 0.000 claims description 145
- 239000005017 polysaccharide Substances 0.000 claims description 145
- 108090000623 proteins and genes Proteins 0.000 claims description 123
- 241000894006 Bacteria Species 0.000 claims description 101
- 102000004169 proteins and genes Human genes 0.000 claims description 66
- 230000015572 biosynthetic process Effects 0.000 claims description 56
- 108010078791 Carrier Proteins Proteins 0.000 claims description 53
- 239000000427 antigen Substances 0.000 claims description 53
- 108091007433 antigens Proteins 0.000 claims description 53
- 102000036639 antigens Human genes 0.000 claims description 53
- 108700005075 Regulator Genes Proteins 0.000 claims description 49
- 230000013595 glycosylation Effects 0.000 claims description 40
- 102000014914 Carrier Proteins Human genes 0.000 claims description 37
- 238000006206 glycosylation reaction Methods 0.000 claims description 31
- 108091008053 gene clusters Proteins 0.000 claims description 30
- 230000000694 effects Effects 0.000 claims description 23
- 230000014509 gene expression Effects 0.000 claims description 23
- 108010089072 Dolichyl-diphosphooligosaccharide-protein glycotransferase Proteins 0.000 claims description 22
- 102000051366 Glycosyltransferases Human genes 0.000 claims description 22
- 108700023372 Glycosyltransferases Proteins 0.000 claims description 22
- RPKLZQLYODPWTM-KBMWBBLPSA-N cholanoic acid Chemical compound C1CC2CCCC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@@H](CCC(O)=O)C)[C@@]1(C)CC2 RPKLZQLYODPWTM-KBMWBBLPSA-N 0.000 claims description 21
- 102000004190 Enzymes Human genes 0.000 claims description 18
- 108090000790 Enzymes Proteins 0.000 claims description 18
- 102000003886 Glycoproteins Human genes 0.000 claims description 18
- 108090000288 Glycoproteins Proteins 0.000 claims description 18
- 101000855412 Homo sapiens Carbamoyl-phosphate synthase [ammonia], mitochondrial Proteins 0.000 claims description 17
- 101000983292 Homo sapiens N-fatty-acyl-amino acid synthase/hydrolase PM20D1 Proteins 0.000 claims description 17
- 101000861263 Homo sapiens Steroid 21-hydroxylase Proteins 0.000 claims description 17
- 241000589875 Campylobacter jejuni Species 0.000 claims description 16
- 102000009016 Cholera Toxin Human genes 0.000 claims description 16
- 108010049048 Cholera Toxin Proteins 0.000 claims description 16
- 241000193998 Streptococcus pneumoniae Species 0.000 claims description 16
- UFPHFKCTOZIAFY-NTDVEAECSA-N ditrans,polycis-undecaprenyl phosphate Chemical compound CC(C)=CCC\C(C)=C\CC\C(C)=C\CC\C(C)=C/CC\C(C)=C/CC\C(C)=C/CC\C(C)=C/CC\C(C)=C/CC\C(C)=C/CC\C(C)=C/CC\C(C)=C/COP(O)(O)=O UFPHFKCTOZIAFY-NTDVEAECSA-N 0.000 claims description 16
- 229940031000 streptococcus pneumoniae Drugs 0.000 claims description 16
- 102000004357 Transferases Human genes 0.000 claims description 15
- 108090000992 Transferases Proteins 0.000 claims description 15
- 108091035707 Consensus sequence Proteins 0.000 claims description 14
- 239000013598 vector Substances 0.000 claims description 11
- 241000588722 Escherichia Species 0.000 claims description 10
- 101710146739 Enterotoxin Proteins 0.000 claims description 8
- 239000000147 enterotoxin Substances 0.000 claims description 8
- 231100000655 enterotoxin Toxicity 0.000 claims description 8
- 150000007523 nucleic acids Chemical class 0.000 claims description 8
- 108020004707 nucleic acids Proteins 0.000 claims description 7
- 102000039446 nucleic acids Human genes 0.000 claims description 7
- 101150084573 CPS5 gene Proteins 0.000 claims description 6
- 108010071134 CRM197 (non-toxic variant of diphtheria toxin) Proteins 0.000 claims description 6
- 101100221536 Dictyostelium discoideum comA gene Proteins 0.000 claims description 6
- 241000194032 Enterococcus faecalis Species 0.000 claims description 6
- 101100434240 Schizosaccharomyces pombe (strain 972 / ATCC 24843) act1 gene Proteins 0.000 claims description 6
- 241000191967 Staphylococcus aureus Species 0.000 claims description 6
- HSCJRCZFDFQWRP-JZMIEXBBSA-N UDP-alpha-D-glucose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OP(O)(=O)OP(O)(=O)OC[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C(NC(=O)C=C2)=O)O1 HSCJRCZFDFQWRP-JZMIEXBBSA-N 0.000 claims description 6
- HSCJRCZFDFQWRP-UHFFFAOYSA-N Uridindiphosphoglukose Natural products OC1C(O)C(O)C(CO)OC1OP(O)(=O)OP(O)(=O)OCC1C(O)C(O)C(N2C(NC(=O)C=C2)=O)O1 HSCJRCZFDFQWRP-UHFFFAOYSA-N 0.000 claims description 6
- 229940032049 enterococcus faecalis Drugs 0.000 claims description 6
- 101710082714 Exotoxin A Proteins 0.000 claims description 5
- 241000607142 Salmonella Species 0.000 claims description 5
- 241000193985 Streptococcus agalactiae Species 0.000 claims description 5
- 229960003983 diphtheria toxoid Drugs 0.000 claims description 5
- 230000001965 increasing effect Effects 0.000 claims description 5
- 229960000814 tetanus toxoid Drugs 0.000 claims description 5
- 101710198480 Clumping factor A Proteins 0.000 claims description 4
- 101710198481 Clumping factor B Proteins 0.000 claims description 4
- 101710147195 Hemolysin A Proteins 0.000 claims description 4
- 101710183389 Pneumolysin Proteins 0.000 claims description 4
- 241000589516 Pseudomonas Species 0.000 claims description 4
- 241000607768 Shigella Species 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- RJMZIUFNDNYWDU-UHFFFAOYSA-N 3-chloro-2-hydroxy-5-phenylbenzoic acid Chemical compound ClC1=C(O)C(C(=O)O)=CC(C=2C=CC=CC=2)=C1 RJMZIUFNDNYWDU-UHFFFAOYSA-N 0.000 claims description 3
- 101100453077 Botryococcus braunii HDR gene Proteins 0.000 claims description 3
- 101150018690 CPS2 gene Proteins 0.000 claims description 3
- 101100080971 Caenorhabditis elegans cps-6 gene Proteins 0.000 claims description 3
- 102100032219 Cathepsin D Human genes 0.000 claims description 3
- 101100002119 Gallus gallus ARF5 gene Proteins 0.000 claims description 3
- 101000869010 Homo sapiens Cathepsin D Proteins 0.000 claims description 3
- 101000933173 Homo sapiens Pro-cathepsin H Proteins 0.000 claims description 3
- 241000588748 Klebsiella Species 0.000 claims description 3
- 241000588653 Neisseria Species 0.000 claims description 3
- 108700026244 Open Reading Frames Proteins 0.000 claims description 3
- 102100025974 Pro-cathepsin H Human genes 0.000 claims description 3
- 101000632473 Rattus norvegicus Pulmonary surfactant-associated protein D Proteins 0.000 claims description 3
- 101100095734 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) SHG1 gene Proteins 0.000 claims description 3
- 101100257577 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) SPP1 gene Proteins 0.000 claims description 3
- 101100020327 Salvia divinorum KPS gene Proteins 0.000 claims description 3
- 241000191940 Staphylococcus Species 0.000 claims description 3
- 241000607734 Yersinia <bacteria> Species 0.000 claims description 3
- 101150002095 capB gene Proteins 0.000 claims description 3
- 101150118250 capC gene Proteins 0.000 claims description 3
- 101150064899 capa gene Proteins 0.000 claims description 3
- HHTOWVWIVBSOKC-UHFFFAOYSA-N cis,trans-5'-hydroxythalidomide Chemical compound O=C1NC(=O)C(O)CC1N1C(=O)C2=CC=CC=C2C1=O HHTOWVWIVBSOKC-UHFFFAOYSA-N 0.000 claims description 3
- 101150075361 cps3 gene Proteins 0.000 claims description 3
- 101150057996 rfaL gene Proteins 0.000 claims description 3
- LZHQPJSJEITGHB-UHFFFAOYSA-N 2-[1-(hydroxymethyl)-2,6-dioxopiperidin-3-yl]isoindole-1,3-dione Chemical compound O=C1N(CO)C(=O)CCC1N1C(=O)C2=CC=CC=C2C1=O LZHQPJSJEITGHB-UHFFFAOYSA-N 0.000 claims description 2
- 101100114734 Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4) cpsD gene Proteins 0.000 claims description 2
- 241000607598 Vibrio Species 0.000 claims description 2
- 238000012258 culturing Methods 0.000 claims description 2
- 230000010076 replication Effects 0.000 claims description 2
- 102100026422 Carbamoyl-phosphate synthase [ammonia], mitochondrial Human genes 0.000 claims 1
- 241001302584 Escherichia coli str. K-12 substr. W3110 Species 0.000 claims 1
- 210000004027 cell Anatomy 0.000 abstract description 68
- 239000000203 mixture Substances 0.000 abstract description 8
- 238000001727 in vivo Methods 0.000 abstract description 5
- 210000001236 prokaryotic cell Anatomy 0.000 abstract description 2
- 235000018102 proteins Nutrition 0.000 description 62
- 101150020532 CPS4 gene Proteins 0.000 description 43
- 238000004458 analytical method Methods 0.000 description 32
- 150000002482 oligosaccharides Chemical class 0.000 description 29
- 239000013612 plasmid Substances 0.000 description 26
- 230000001580 bacterial effect Effects 0.000 description 24
- 235000000346 sugar Nutrition 0.000 description 24
- 238000003786 synthesis reaction Methods 0.000 description 22
- 229960005486 vaccine Drugs 0.000 description 22
- 102100026873 N-fatty-acyl-amino acid synthase/hydrolase PM20D1 Human genes 0.000 description 16
- 230000004988 N-glycosylation Effects 0.000 description 16
- 239000002158 endotoxin Substances 0.000 description 16
- 229940088598 enzyme Drugs 0.000 description 16
- 150000002632 lipids Chemical class 0.000 description 16
- 229920006008 lipopolysaccharide Polymers 0.000 description 16
- 108010060123 Conjugate Vaccines Proteins 0.000 description 15
- 229930186217 Glycolipid Natural products 0.000 description 15
- 241000606999 Plesiomonas shigelloides Species 0.000 description 15
- 230000001851 biosynthetic effect Effects 0.000 description 14
- 230000006696 biosynthetic metabolic pathway Effects 0.000 description 14
- 229940031670 conjugate vaccine Drugs 0.000 description 14
- 230000037361 pathway Effects 0.000 description 14
- 238000004885 tandem mass spectrometry Methods 0.000 description 13
- 241000192125 Firmicutes Species 0.000 description 12
- 241000607760 Shigella sonnei Species 0.000 description 11
- 235000001014 amino acid Nutrition 0.000 description 11
- 229940024606 amino acid Drugs 0.000 description 11
- 150000001413 amino acids Chemical group 0.000 description 11
- 230000002068 genetic effect Effects 0.000 description 11
- 239000012528 membrane Substances 0.000 description 11
- 238000001262 western blot Methods 0.000 description 11
- 108010067770 Endopeptidase K Proteins 0.000 description 10
- 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 10
- 238000012512 characterization method Methods 0.000 description 10
- 239000008103 glucose Substances 0.000 description 10
- 108700014210 glycosyltransferase activity proteins Proteins 0.000 description 10
- 150000002772 monosaccharides Chemical class 0.000 description 10
- 229920001542 oligosaccharide Polymers 0.000 description 10
- 241000283973 Oryctolagus cuniculus Species 0.000 description 9
- 102000004879 Racemases and epimerases Human genes 0.000 description 9
- 108090001066 Racemases and epimerases Proteins 0.000 description 9
- NTXGVHCCXVHYCL-RDQGWRCRSA-N all-trans-undecaprenyl diphosphate Chemical compound CC(C)=CCC\C(C)=C\CC\C(C)=C\CC\C(C)=C\CC\C(C)=C\CC\C(C)=C\CC\C(C)=C\CC\C(C)=C\CC\C(C)=C\CC\C(C)=C\CC\C(C)=C\COP(O)(=O)OP(O)(O)=O NTXGVHCCXVHYCL-RDQGWRCRSA-N 0.000 description 9
- 239000002775 capsule Substances 0.000 description 9
- 230000006870 function Effects 0.000 description 9
- 230000008520 organization Effects 0.000 description 9
- 238000000746 purification Methods 0.000 description 9
- 238000012546 transfer Methods 0.000 description 9
- 101150105594 SCM3 gene Proteins 0.000 description 8
- 239000000284 extract Substances 0.000 description 8
- 108090000765 processed proteins & peptides Proteins 0.000 description 8
- 208000035109 Pneumococcal Infections Diseases 0.000 description 7
- OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 7
- 150000001720 carbohydrates Chemical class 0.000 description 7
- 238000012217 deletion Methods 0.000 description 7
- 230000037430 deletion Effects 0.000 description 7
- 239000000499 gel Substances 0.000 description 7
- 230000003053 immunization Effects 0.000 description 7
- 238000002649 immunization Methods 0.000 description 7
- 208000015181 infectious disease Diseases 0.000 description 7
- 239000002773 nucleotide Substances 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 241000606768 Haemophilus influenzae Species 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- -1 dolichol phosphate Chemical class 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 125000003729 nucleotide group Chemical group 0.000 description 6
- 229940115939 shigella sonnei Drugs 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 239000002028 Biomass Substances 0.000 description 5
- 239000007987 MES buffer Substances 0.000 description 5
- 229910019142 PO4 Inorganic materials 0.000 description 5
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 5
- 238000010586 diagram Methods 0.000 description 5
- 230000028993 immune response Effects 0.000 description 5
- 230000005847 immunogenicity Effects 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 239000003999 initiator Substances 0.000 description 5
- 230000010354 integration Effects 0.000 description 5
- 239000010452 phosphate Substances 0.000 description 5
- 230000032258 transport Effects 0.000 description 5
- HVCOBJNICQPDBP-UHFFFAOYSA-N 3-[3-[3,5-dihydroxy-6-methyl-4-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyoxan-2-yl]oxydecanoyloxy]decanoic acid;hydrate Chemical compound O.OC1C(OC(CC(=O)OC(CCCCCCC)CC(O)=O)CCCCCCC)OC(C)C(O)C1OC1C(O)C(O)C(O)C(C)O1 HVCOBJNICQPDBP-UHFFFAOYSA-N 0.000 description 4
- 101100248157 Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720) rfbP gene Proteins 0.000 description 4
- 101001010097 Shigella phage SfV Bactoprenol-linked glucose translocase Proteins 0.000 description 4
- 230000033228 biological regulation Effects 0.000 description 4
- 235000014633 carbohydrates Nutrition 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 235000011180 diphosphates Nutrition 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 101150002054 galE gene Proteins 0.000 description 4
- 238000012252 genetic analysis Methods 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 230000001939 inductive effect Effects 0.000 description 4
- 238000002372 labelling Methods 0.000 description 4
- 229940031999 pneumococcal conjugate vaccine Drugs 0.000 description 4
- 239000002243 precursor Substances 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 239000012474 protein marker Substances 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 4
- 241000589876 Campylobacter Species 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- 108010055629 Glucosyltransferases Proteins 0.000 description 3
- 102000000340 Glucosyltransferases Human genes 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- OVRNDRQMDRJTHS-KEWYIRBNSA-N N-acetyl-D-galactosamine Chemical compound CC(=O)N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-KEWYIRBNSA-N 0.000 description 3
- MBLBDJOUHNCFQT-UHFFFAOYSA-N N-acetyl-D-galactosamine Natural products CC(=O)NC(C=O)C(O)C(O)C(O)CO MBLBDJOUHNCFQT-UHFFFAOYSA-N 0.000 description 3
- 241000588650 Neisseria meningitidis Species 0.000 description 3
- 239000000020 Nitrocellulose Substances 0.000 description 3
- 108091028043 Nucleic acid sequence Proteins 0.000 description 3
- 108091005804 Peptidases Proteins 0.000 description 3
- 102000035195 Peptidases Human genes 0.000 description 3
- 239000004365 Protease Substances 0.000 description 3
- 241001138501 Salmonella enterica Species 0.000 description 3
- 210000001744 T-lymphocyte Anatomy 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 230000000890 antigenic effect Effects 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 230000001086 cytosolic effect Effects 0.000 description 3
- 238000001212 derivatisation Methods 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 101150045804 dexB gene Proteins 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 150000002016 disaccharides Chemical class 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 238000013467 fragmentation Methods 0.000 description 3
- 238000006062 fragmentation reaction Methods 0.000 description 3
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 3
- 230000006801 homologous recombination Effects 0.000 description 3
- 238000002744 homologous recombination Methods 0.000 description 3
- 210000000987 immune system Anatomy 0.000 description 3
- 230000002779 inactivation Effects 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 230000005923 long-lasting effect Effects 0.000 description 3
- 229920001220 nitrocellulos Polymers 0.000 description 3
- 230000001717 pathogenic effect Effects 0.000 description 3
- 210000001322 periplasm Anatomy 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 150000004804 polysaccharides Polymers 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 235000019419 proteases Nutrition 0.000 description 3
- 230000001681 protective effect Effects 0.000 description 3
- 101150117960 rcsA gene Proteins 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 150000008163 sugars Chemical class 0.000 description 3
- 101100222094 Arabidopsis thaliana CSP4 gene Proteins 0.000 description 2
- 241000203069 Archaea Species 0.000 description 2
- 208000035143 Bacterial infection Diseases 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 208000035473 Communicable disease Diseases 0.000 description 2
- AEMOLEFTQBMNLQ-YMDCURPLSA-N D-galactopyranuronic acid Chemical group OC1O[C@H](C(O)=O)[C@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-YMDCURPLSA-N 0.000 description 2
- 102000016607 Diphtheria Toxin Human genes 0.000 description 2
- 108010053187 Diphtheria Toxin Proteins 0.000 description 2
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 2
- 241000206602 Eukaryota Species 0.000 description 2
- 102000002068 Glycopeptides Human genes 0.000 description 2
- 108010015899 Glycopeptides Proteins 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 108090000301 Membrane transport proteins Proteins 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 206010035664 Pneumonia Diseases 0.000 description 2
- 229940124950 Prevnar 13 Drugs 0.000 description 2
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
- 241000194017 Streptococcus Species 0.000 description 2
- 241000193990 Streptococcus sp. 'group B' Species 0.000 description 2
- XCCTYIAWTASOJW-UHFFFAOYSA-N UDP-Glc Natural products OC1C(O)C(COP(O)(=O)OP(O)(O)=O)OC1N1C(=O)NC(=O)C=C1 XCCTYIAWTASOJW-UHFFFAOYSA-N 0.000 description 2
- 238000010306 acid treatment Methods 0.000 description 2
- 125000003275 alpha amino acid group Chemical group 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 2
- 208000022362 bacterial infectious disease Diseases 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000002759 chromosomal effect Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000010230 functional analysis Methods 0.000 description 2
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 2
- 229940045808 haemophilus influenzae type b Drugs 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 238000003119 immunoblot Methods 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 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 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- 230000001662 opsonic effect Effects 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 229940124733 pneumococcal vaccine Drugs 0.000 description 2
- 229960001973 pneumococcal vaccines Drugs 0.000 description 2
- 238000006116 polymerization reaction Methods 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 230000008093 supporting effect Effects 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 2
- 230000001018 virulence Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 101150018163 wcaJ gene Proteins 0.000 description 2
- 101150017134 wecA gene Proteins 0.000 description 2
- IAJILQKETJEXLJ-STGXQOJASA-N (2s,3s,4r,5s)-2,3,4,5-tetrahydroxy-6-oxohexanoic acid Chemical group O=C[C@@H](O)[C@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-STGXQOJASA-N 0.000 description 1
- 229940031767 13-valent pneumococcal conjugate vaccine Drugs 0.000 description 1
- GGHDSBMLSIVVPC-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-4,7-dimethylisoindole-1,3-dione Chemical compound O=C1C=2C(C)=CC=C(C)C=2C(=O)N1C1=CC=C(F)C=C1F GGHDSBMLSIVVPC-UHFFFAOYSA-N 0.000 description 1
- VKJOGYLRXNAHPO-UHFFFAOYSA-N 2-aminobenzamide Chemical compound NC(=O)C1=CC=CC=C1N.NC(=O)C1=CC=CC=C1N VKJOGYLRXNAHPO-UHFFFAOYSA-N 0.000 description 1
- WZRJTRPJURQBRM-UHFFFAOYSA-N 4-amino-n-(5-methyl-1,2-oxazol-3-yl)benzenesulfonamide;5-[(3,4,5-trimethoxyphenyl)methyl]pyrimidine-2,4-diamine Chemical compound O1C(C)=CC(NS(=O)(=O)C=2C=CC(N)=CC=2)=N1.COC1=C(OC)C(OC)=CC(CC=2C(=NC(N)=NC=2)N)=C1 WZRJTRPJURQBRM-UHFFFAOYSA-N 0.000 description 1
- VEOGKKIBNYROKA-UHFFFAOYSA-N 5-ethyl-1-phenyl-5-(4,5,6,7-tetrafluoro-1,3-dioxoisoindol-2-yl)-1,3-diazinane-2,4,6-trione Chemical compound O=C1C(CC)(N2C(C3=C(C(=C(F)C(F)=C3F)F)C2=O)=O)C(=O)NC(=O)N1C1=CC=CC=C1 VEOGKKIBNYROKA-UHFFFAOYSA-N 0.000 description 1
- 241000589291 Acinetobacter Species 0.000 description 1
- 244000034356 Aframomum angustifolium Species 0.000 description 1
- 201000001178 Bacterial Pneumonia Diseases 0.000 description 1
- 108010077805 Bacterial Proteins Proteins 0.000 description 1
- 241000588807 Bordetella Species 0.000 description 1
- 241000588780 Bordetella parapertussis Species 0.000 description 1
- 241000589969 Borreliella burgdorferi Species 0.000 description 1
- 241000722910 Burkholderia mallei Species 0.000 description 1
- 241001136175 Burkholderia pseudomallei Species 0.000 description 1
- 102100021935 C-C motif chemokine 26 Human genes 0.000 description 1
- 241000589994 Campylobacter sp. Species 0.000 description 1
- 241000222122 Candida albicans Species 0.000 description 1
- 241000606153 Chlamydia trachomatis Species 0.000 description 1
- 241000193163 Clostridioides difficile Species 0.000 description 1
- 241000193468 Clostridium perfringens Species 0.000 description 1
- 102100037840 Dehydrogenase/reductase SDR family member 2, mitochondrial Human genes 0.000 description 1
- 102100031780 Endonuclease Human genes 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 241000305071 Enterobacterales Species 0.000 description 1
- 101100156625 Escherichia coli (strain K12) wcaJ gene Proteins 0.000 description 1
- 241001646716 Escherichia coli K-12 Species 0.000 description 1
- 108700039887 Essential Genes Proteins 0.000 description 1
- 108010000916 Fimbriae Proteins Proteins 0.000 description 1
- 241000589602 Francisella tularensis Species 0.000 description 1
- 240000006509 Gynostemma pentaphyllum Species 0.000 description 1
- 235000002956 Gynostemma pentaphyllum Nutrition 0.000 description 1
- 238000011993 High Performance Size Exclusion Chromatography Methods 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000897493 Homo sapiens C-C motif chemokine 26 Proteins 0.000 description 1
- 101000902641 Homo sapiens Protein dpy-30 homolog Proteins 0.000 description 1
- 241000588747 Klebsiella pneumoniae Species 0.000 description 1
- 241000588754 Klebsiella sp. Species 0.000 description 1
- 241000589242 Legionella pneumophila Species 0.000 description 1
- 241000222732 Leishmania major Species 0.000 description 1
- 108090000364 Ligases Proteins 0.000 description 1
- 102000003960 Ligases Human genes 0.000 description 1
- 241000186779 Listeria monocytogenes Species 0.000 description 1
- 241001084338 Listeria sp. Species 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 102000003939 Membrane transport proteins Human genes 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- 102000016943 Muramidase Human genes 0.000 description 1
- 108010014251 Muramidase Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 1
- XOCCAGJZGBCJME-VAYLDTTESA-N N-Acetyl-L-Fucosamine Chemical compound C[C@@H]1OC(O)[C@@H](NC(C)=O)[C@H](O)[C@@H]1O XOCCAGJZGBCJME-VAYLDTTESA-N 0.000 description 1
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 1
- OVRNDRQMDRJTHS-RTRLPJTCSA-N N-acetyl-D-glucosamine Chemical compound CC(=O)N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-RTRLPJTCSA-N 0.000 description 1
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 101710160107 Outer membrane protein A Proteins 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
- 208000009362 Pneumococcal Pneumonia Diseases 0.000 description 1
- 206010035728 Pneumonia pneumococcal Diseases 0.000 description 1
- 101710188053 Protein D Proteins 0.000 description 1
- 102100022946 Protein dpy-30 homolog Human genes 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 241000589774 Pseudomonas sp. Species 0.000 description 1
- 101710086831 Putative acetyltransferase Proteins 0.000 description 1
- 102000018120 Recombinases Human genes 0.000 description 1
- 108010091086 Recombinases Proteins 0.000 description 1
- 101710132893 Resolvase Proteins 0.000 description 1
- 101100311558 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) SWD2 gene Proteins 0.000 description 1
- 241000533331 Salmonella bongori Species 0.000 description 1
- 241000607356 Salmonella enterica subsp. arizonae Species 0.000 description 1
- 241000607361 Salmonella enterica subsp. enterica Species 0.000 description 1
- 241000607358 Salmonella enterica subsp. salamae Species 0.000 description 1
- 229940124842 Salmonella vaccine Drugs 0.000 description 1
- 101100043583 Schizosaccharomyces pombe (strain 972 / ATCC 24843) sst6 gene Proteins 0.000 description 1
- 108091058545 Secretory proteins Proteins 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 241000607762 Shigella flexneri Species 0.000 description 1
- 101800004706 Somatostatin-22 Proteins 0.000 description 1
- 241000193996 Streptococcus pyogenes Species 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 101000980463 Treponema pallidum (strain Nichols) Chaperonin GroEL Proteins 0.000 description 1
- XCCTYIAWTASOJW-XVFCMESISA-N Uridine-5'-Diphosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(=O)NC(=O)C=C1 XCCTYIAWTASOJW-XVFCMESISA-N 0.000 description 1
- 241000607626 Vibrio cholerae Species 0.000 description 1
- INJACODUUNZJCO-QLGOPVMHSA-N [(2r,3r,4r,5r,6r)-3-acetamido-4,5-dihydroxy-6-methyloxan-2-yl] [[(2r,3s,4r,5r)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] hydrogen phosphate Chemical compound CC(=O)N[C@@H]1[C@@H](O)[C@@H](O)[C@@H](C)O[C@@H]1OP(O)(=O)OP(O)(=O)OC[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C(NC(=O)C=C2)=O)O1 INJACODUUNZJCO-QLGOPVMHSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- MBLBDJOUHNCFQT-WCTZXXKLSA-N aldehydo-N-acetyl-D-mannosamine Chemical compound CC(=O)N[C@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-WCTZXXKLSA-N 0.000 description 1
- GUSANBRNBREBPL-TZTIVRRBSA-N alpha-D-Ara-(1->5)-alpha-D-Ara-(1->3)-[alpha-D-Ara-(1->5)]-alpha-D-Ara-(1->5)-alpha-D-Ara-(1->5)-alpha-D-Ara-(1->2)-[alpha-D-Man-(1->6)]-alpha-D-Man-(1->6)-[alpha-D-Man-(1->2)]-alpha-D-Man-(1->6)-alpha-D-Man-(1->6)-alpha-D-Man Chemical compound OC[C@H]1O[C@H](OC[C@H]2O[C@H](O[C@H]3[C@H](O)[C@@H](OC[C@H]4O[C@H](OC[C@H]5O[C@H](O[C@H]6[C@@H](O)[C@H](O)[C@@H](CO[C@H]7O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]7O)O[C@@H]6OC[C@H]6O[C@H](OC[C@H]7O[C@H](OC[C@H]8O[C@H](O)[C@@H](O)[C@@H](O)[C@@H]8O)[C@@H](O)[C@@H](O)[C@@H]7O)[C@@H](O[C@H]7O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]7O)[C@@H](O)[C@@H]6O)[C@@H](O)[C@@H]5O)[C@@H](O)[C@@H]4O)O[C@@H]3CO[C@H]3O[C@H](CO)[C@@H](O)[C@@H]3O)[C@@H](O)[C@@H]2O)[C@@H](O)[C@@H]1O GUSANBRNBREBPL-TZTIVRRBSA-N 0.000 description 1
- AEMOLEFTQBMNLQ-BKBMJHBISA-N alpha-D-galacturonic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-BKBMJHBISA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229910021502 aluminium hydroxide Inorganic materials 0.000 description 1
- 238000012801 analytical assay Methods 0.000 description 1
- 238000005571 anion exchange chromatography Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000003497 anti-pneumococcal effect Effects 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- 210000003578 bacterial chromosome Anatomy 0.000 description 1
- 230000007924 bacterial virulence factor Effects 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- 230000008238 biochemical pathway Effects 0.000 description 1
- 238000003766 bioinformatics method Methods 0.000 description 1
- 208000037815 bloodstream infection Diseases 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 229940074375 burkholderia mallei Drugs 0.000 description 1
- 229940095731 candida albicans Drugs 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000008614 cellular interaction Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 239000013043 chemical agent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229940038705 chlamydia trachomatis Drugs 0.000 description 1
- 229960005091 chloramphenicol Drugs 0.000 description 1
- 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 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 208000035850 clinical syndrome Diseases 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 229940047766 co-trimoxazole Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 108091036078 conserved sequence Proteins 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 101150047356 dec-1 gene Proteins 0.000 description 1
- 238000005034 decoration Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 239000001177 diphosphate Substances 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-N diphosphoric acid Chemical compound OP(O)(=O)OP(O)(O)=O XPPKVPWEQAFLFU-UHFFFAOYSA-N 0.000 description 1
- QELUYTUMUWHWMC-UHFFFAOYSA-N edaravone Chemical compound O=C1CC(C)=NN1C1=CC=CC=C1 QELUYTUMUWHWMC-UHFFFAOYSA-N 0.000 description 1
- 238000002101 electrospray ionisation tandem mass spectrometry Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 238000006345 epimerization reaction Methods 0.000 description 1
- 229960003276 erythromycin Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 238000001215 fluorescent labelling Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 244000078673 foodborn pathogen Species 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229940118764 francisella tularensis Drugs 0.000 description 1
- 102000035122 glycosylated proteins Human genes 0.000 description 1
- 108091005608 glycosylated proteins Proteins 0.000 description 1
- 229930004094 glycosylphosphatidylinositol Natural products 0.000 description 1
- 210000002288 golgi apparatus Anatomy 0.000 description 1
- 244000000059 gram-positive pathogen Species 0.000 description 1
- 150000002402 hexoses Chemical class 0.000 description 1
- 244000052637 human pathogen Species 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 238000002013 hydrophilic interaction chromatography Methods 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- 208000022760 infectious otitis media Diseases 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 238000001155 isoelectric focusing Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 229960000318 kanamycin Drugs 0.000 description 1
- 229930027917 kanamycin Natural products 0.000 description 1
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 1
- 229930182823 kanamycin A Natural products 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 229940115932 legionella pneumophila Drugs 0.000 description 1
- 238000002789 length control Methods 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- GZQKNULLWNGMCW-PWQABINMSA-N lipid A (E. coli) Chemical group 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
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 229960000274 lysozyme Drugs 0.000 description 1
- 239000004325 lysozyme Substances 0.000 description 1
- 235000010335 lysozyme Nutrition 0.000 description 1
- 201000004792 malaria Diseases 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 238000001906 matrix-assisted laser desorption--ionisation mass spectrometry Methods 0.000 description 1
- 230000009061 membrane transport Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000007479 molecular analysis Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000004305 normal phase HPLC Methods 0.000 description 1
- 238000006384 oligomerization reaction Methods 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- PXBFMLJZNCDSMP-UHFFFAOYSA-N ortho-aminobenzoylamine Natural products NC(=O)C1=CC=CC=C1N PXBFMLJZNCDSMP-UHFFFAOYSA-N 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000008259 pathway mechanism Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 238000012510 peptide mapping method Methods 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 229940031960 pneumococcal polysaccharide vaccine Drugs 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000012846 protein folding Effects 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 239000011535 reaction buffer Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 210000003660 reticulum Anatomy 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 210000003705 ribosome Anatomy 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000000405 serological effect Effects 0.000 description 1
- 238000012807 shake-flask culturing Methods 0.000 description 1
- 210000002107 sheath cell Anatomy 0.000 description 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 230000010473 stable expression Effects 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 208000022218 streptococcal pneumonia Diseases 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 150000004044 tetrasaccharides Chemical class 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
Classifications
-
- 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
- A61K39/09—Lactobacillales, e.g. aerococcus, enterococcus, lactobacillus, lactococcus, streptococcus
- A61K39/092—Streptococcus
-
- 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
-
- 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
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/70—Vectors or expression systems specially adapted for E. coli
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P21/00—Preparation of peptides or proteins
- C12P21/005—Glycopeptides, glycoproteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/52—Bacterial cells; Fungal cells; Protozoal cells
- A61K2039/523—Bacterial cells; Fungal cells; Protozoal cells expressing foreign proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55505—Inorganic adjuvants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55566—Emulsions, e.g. Freund's adjuvant, MF59
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
- A61K2039/6031—Proteins
- A61K2039/6037—Bacterial toxins, e.g. diphteria toxoid [DT], tetanus toxoid [TT]
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Microbiology (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Immunology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- General Chemical & Material Sciences (AREA)
- Oncology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Peptides Or Proteins (AREA)
- Enzymes And Modification Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261723408P | 2012-11-07 | 2012-11-07 | |
| US61/723,408 | 2012-11-07 | ||
| CA2889767A CA2889767C (en) | 2012-11-07 | 2013-11-07 | Production of recombinant vaccine in e. coli by enzymatic conjugation |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2889767A Division CA2889767C (en) | 2012-11-07 | 2013-11-07 | Production of recombinant vaccine in e. coli by enzymatic conjugation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3125293A1 true CA3125293A1 (en) | 2014-05-15 |
Family
ID=49552366
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3125293A Pending CA3125293A1 (en) | 2012-11-07 | 2013-11-07 | Production of recombinant vaccine in e. coli by enzymatic conjugation |
| CA2889767A Active CA2889767C (en) | 2012-11-07 | 2013-11-07 | Production of recombinant vaccine in e. coli by enzymatic conjugation |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2889767A Active CA2889767C (en) | 2012-11-07 | 2013-11-07 | Production of recombinant vaccine in e. coli by enzymatic conjugation |
Country Status (16)
| Country | Link |
|---|---|
| US (2) | US20150273043A1 (enExample) |
| EP (3) | EP3444352B1 (enExample) |
| JP (2) | JP6412875B2 (enExample) |
| KR (1) | KR20150079964A (enExample) |
| CN (1) | CN105008539B (enExample) |
| AU (2) | AU2013343520B2 (enExample) |
| BR (1) | BR112015010283A8 (enExample) |
| CA (2) | CA3125293A1 (enExample) |
| EA (1) | EA201590705A1 (enExample) |
| ES (3) | ES2882282T3 (enExample) |
| IL (1) | IL238586A0 (enExample) |
| MX (1) | MX366912B (enExample) |
| SG (1) | SG11201503308XA (enExample) |
| TR (1) | TR201903066T4 (enExample) |
| WO (1) | WO2014072405A1 (enExample) |
| ZA (1) | ZA201503097B (enExample) |
Families Citing this family (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2660227T3 (es) * | 2009-11-19 | 2018-03-21 | Glaxosmithkline Biologicals S.A. | Sistema biosintético que produce polisacáridos inmunogénicos en células procariotas |
| CN106062203B (zh) * | 2013-10-11 | 2020-08-07 | 葛兰素史密丝克莱恩生物有限公司 | 宿主细胞修饰的方法 |
| PL3110441T3 (pl) | 2014-02-24 | 2024-08-05 | Glaxosmithkline Biologicals S.A. | Nowatorski polisacharyd i jego zastosowania |
| DK3131577T3 (da) * | 2014-04-17 | 2020-07-13 | Glaxosmithkline Biologicals Sa | Modificerede værtsceller og anvendelser deraf |
| US10307474B2 (en) * | 2014-08-08 | 2019-06-04 | Glaxosmithkline Biologicals S.A. | Modified host cells and hybrid oligosaccharides for use in bioconjugate production |
| ES3039659T3 (en) | 2015-02-26 | 2025-10-23 | Vaxnewmo Llc | Acinetobacter o-oligosaccharyltransferases and uses thereof |
| GB201518668D0 (en) * | 2015-10-21 | 2015-12-02 | Glaxosmithkline Biolog Sa | Immunogenic Comosition |
| GB201610599D0 (en) | 2016-06-17 | 2016-08-03 | Glaxosmithkline Biologicals Sa | Immunogenic Composition |
| CN105963691B (zh) * | 2016-07-03 | 2020-05-01 | 查文娟 | 一种肺炎链球菌疫苗 |
| CN106929573B (zh) * | 2017-02-21 | 2020-06-09 | 南开大学 | 对嗜肺军团菌O12型的wzm和wecA基因特异的核苷酸序列及其应用 |
| GB201712678D0 (en) | 2017-08-07 | 2017-09-20 | Glaxosmithkline Biologicals Sa | Process for the manipulation of nucleic acids |
| WO2019043245A1 (en) * | 2017-09-04 | 2019-03-07 | London School Of Hygiene And Tropical Medicine | MICROBIAL CELLS EXPRESSING STREPTOCOCCAL SERROTYPES |
| US11235046B2 (en) | 2017-11-04 | 2022-02-01 | Nevada Research & Innovation Corporation | Immunogenic conjugates and methods of use thereof |
| GB201721582D0 (en) | 2017-12-21 | 2018-02-07 | Glaxosmithkline Biologicals Sa | S aureus antigens and immunogenic compositions |
| GB201721576D0 (en) | 2017-12-21 | 2018-02-07 | Glaxosmithkline Biologicals Sa | Hla antigens and glycoconjugates thereof |
| WO2019241672A2 (en) | 2018-06-16 | 2019-12-19 | Vaxnewmo Llc | Glycosylated comp pilin variants, methods of making and uses thereof |
| US11260119B2 (en) | 2018-08-24 | 2022-03-01 | Pfizer Inc. | Escherichia coli compositions and methods thereof |
| EP3650044A1 (en) * | 2018-11-06 | 2020-05-13 | ETH Zürich | Anti-glycan vaccines |
| WO2020131236A1 (en) * | 2018-12-21 | 2020-06-25 | Vaxnewmo Llc | O-linked glycosylation recognition motifs |
| IL286467B1 (en) * | 2019-03-18 | 2025-10-01 | Janssen Pharmaceuticals Inc | Methods for producing bioconjugates of E. COLI O-antigen polysaccharides, preparations thereof and methods for using them |
| EP3770269A1 (en) | 2019-07-23 | 2021-01-27 | GlaxoSmithKline Biologicals S.A. | Quantification of bioconjugate glycosylation |
| CN111518738B (zh) * | 2020-05-08 | 2022-02-08 | 徐州海润生物科技有限公司 | 重组卡介苗及其制备方法和应用 |
| CN112369722B (zh) * | 2020-05-08 | 2023-03-17 | 湖北中烟工业有限责任公司 | 加热不燃烧装置和温度控制方法 |
| WO2021255684A1 (en) * | 2020-06-18 | 2021-12-23 | Glaxosmithkline Biologicals Sa | Shigella-tetravalent (shigella4v) bioconjugate |
| CA3185642A1 (en) | 2020-06-25 | 2021-12-30 | Glaxosmithkline Biologicals Sa | Modified exotoxin a proteins |
| PE20231385A1 (es) | 2020-09-17 | 2023-09-12 | Janssen Pharmaceuticals Inc | Composiciones de vacunas multivalentes y usos de las mismas |
| US12138302B2 (en) | 2020-10-27 | 2024-11-12 | Pfizer Inc. | Escherichia coli compositions and methods thereof |
| US12357681B2 (en) | 2020-12-23 | 2025-07-15 | Pfizer Inc. | E. coli FimH mutants and uses thereof |
| WO2023118033A1 (en) | 2021-12-22 | 2023-06-29 | Glaxosmithkline Biologicals Sa | Vaccine |
| GB202302579D0 (en) | 2023-02-23 | 2023-04-12 | Glaxosmithkline Biologicals Sa | Immunogenic composition |
| WO2025172892A1 (en) | 2024-02-16 | 2025-08-21 | Glaxosmithkline Biologicals Sa | Modified proteins and methods |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2638595A (en) * | 1994-05-16 | 1995-12-05 | Uab Research Foundation, The | (streptococcus pneumoniae) capsular polysaccharide genes and flanking regions |
| US7018637B2 (en) | 1998-02-23 | 2006-03-28 | Aventis Pasteur, Inc | Multi-oligosaccharide glycoconjugate bacterial meningitis vaccines |
| US7541043B2 (en) | 2002-01-16 | 2009-06-02 | The United States Of America As Represented By The Department Of Health And Human Services | Vaccine for protection against Shigella sonnei disease |
| DK1481057T3 (da) | 2002-03-07 | 2006-05-15 | Eidgenoess Tech Hochschule | System og fremgangsmåde til fremstilling af rekombinante glycosylerede proteiner i en prokaryot vært |
| KR101524636B1 (ko) | 2005-05-11 | 2015-06-03 | 에테하 취리히 | 원핵 세포로부터의 재조합 ｎ-글리코실화 단백질 |
| US8895014B2 (en) | 2008-02-20 | 2014-11-25 | Glycovaxyn Ag | Bioconjugates made from recombinant N-glycosylated proteins from procaryotic cells |
| JP5841044B2 (ja) * | 2009-03-23 | 2016-01-06 | 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． | 複合糖質ワクチン |
| EP2453762A4 (en) | 2009-07-17 | 2014-06-25 | Ocean Harvest Technology Canada Inc | NATURAL AND SUSTAINABLE ALGAE FORMULA THAT REPLACES SYNTHETIC ADDITIVES IN THE FEEDING OF SALMON |
| PL2566507T3 (pl) | 2010-05-06 | 2018-05-30 | Glaxosmithkline Biologicals Sa | Szczepionki na bazie biokoniugatu przeciw otoczkowym bakteriom gram-dodatnim |
| EP2906681B1 (en) * | 2012-10-12 | 2019-01-09 | GlaxoSmithKline Biologicals S.A. | Methods of host cell modification |
-
2013
- 2013-11-07 ES ES18211761T patent/ES2882282T3/es active Active
- 2013-11-07 CA CA3125293A patent/CA3125293A1/en active Pending
- 2013-11-07 EP EP18198665.4A patent/EP3444352B1/en active Active
- 2013-11-07 SG SG11201503308XA patent/SG11201503308XA/en unknown
- 2013-11-07 AU AU2013343520A patent/AU2013343520B2/en not_active Ceased
- 2013-11-07 ES ES13788753T patent/ES2713166T3/es active Active
- 2013-11-07 TR TR2019/03066T patent/TR201903066T4/tr unknown
- 2013-11-07 JP JP2015541130A patent/JP6412875B2/ja not_active Expired - Fee Related
- 2013-11-07 EA EA201590705A patent/EA201590705A1/ru unknown
- 2013-11-07 EP EP13788753.5A patent/EP2917351B1/en active Active
- 2013-11-07 MX MX2015005797A patent/MX366912B/es active IP Right Grant
- 2013-11-07 BR BR112015010283A patent/BR112015010283A8/pt not_active Application Discontinuation
- 2013-11-07 KR KR1020157014830A patent/KR20150079964A/ko not_active Withdrawn
- 2013-11-07 US US14/440,311 patent/US20150273043A1/en not_active Abandoned
- 2013-11-07 WO PCT/EP2013/073266 patent/WO2014072405A1/en not_active Ceased
- 2013-11-07 CN CN201380069524.XA patent/CN105008539B/zh not_active Expired - Fee Related
- 2013-11-07 ES ES18198665T patent/ES2848774T3/es active Active
- 2013-11-07 EP EP18211761.4A patent/EP3508579B1/en active Active
- 2013-11-07 CA CA2889767A patent/CA2889767C/en active Active
-
2015
- 2015-05-03 IL IL238586A patent/IL238586A0/en unknown
- 2015-05-06 ZA ZA2015/03097A patent/ZA201503097B/en unknown
-
2017
- 2017-12-20 AU AU2017279688A patent/AU2017279688B2/en not_active Ceased
-
2018
- 2018-07-13 US US16/034,906 patent/US10973901B2/en not_active Expired - Fee Related
- 2018-10-01 JP JP2018186302A patent/JP6833785B2/ja not_active Expired - Fee Related
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2017279688B2 (en) | Production of recombinant vaccine in e. coli by enzymatic conjugation | |
| JP6435583B2 (ja) | 莢膜グラム陽性菌のバイオコンジュゲートワクチン | |
| TWI751513B (zh) | E. coli O-抗原多醣生物結合物、其製備方法及其使用方法 | |
| JP6682451B2 (ja) | 改変型宿主細胞およびその使用 | |
| CN106535927A (zh) | 新颖多糖及其用途 | |
| US12350342B2 (en) | O-linked glycosylation recognition motifs | |
| JP2023531242A (ja) | 改変Ｅｘｏｔｏｘｉｎ Ａタンパク質 | |
| CN113950524A (zh) | 生产大肠杆菌o-抗原多糖的生物缀合物的方法、其组合物及其使用方法 | |
| US20220054632A1 (en) | Modified carrier proteins for o-linked glycosylation | |
| Duke et al. | Development and immunogenicity of a prototype multivalent group B Streptococcus bioconjugate vaccine | |
| JP2024517754A (ja) | Ｏ－結合型グリコシル化に十分な最小シークオン | |
| CN120897997A (zh) | 用于生产具有与第二多肽配偶体的异肽键的糖缀合物多肽的组合物和方法以及这些糖缀合物多肽的用途 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20210720 |
|
| EEER | Examination request |
Effective date: 20210720 |
|
| EEER | Examination request |
Effective date: 20210720 |
|
| EEER | Examination request |
Effective date: 20210720 |
|
| EEER | Examination request |
Effective date: 20210720 |
|
| EEER | Examination request |
Effective date: 20210720 |
|
| EEER | Examination request |
Effective date: 20210720 |
|
| EEER | Examination request |
Effective date: 20210720 |
|
| EEER | Examination request |
Effective date: 20210720 |
|
| EEER | Examination request |
Effective date: 20210720 |
|
| EEER | Examination request |
Effective date: 20210720 |