ES2367918T5 - Procedimiento de fabricación de vacunas - Google Patents
Procedimiento de fabricación de vacunas Download PDFInfo
- Publication number
- ES2367918T5 ES2367918T5 ES06754611.9T ES06754611T ES2367918T5 ES 2367918 T5 ES2367918 T5 ES 2367918T5 ES 06754611 T ES06754611 T ES 06754611T ES 2367918 T5 ES2367918 T5 ES 2367918T5
- Authority
- ES
- Spain
- Prior art keywords
- saccharide
- protein
- minutes
- aliquot
- carbodiimide
- 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
- 229960005486 vaccine Drugs 0.000 title claims description 31
- 238000004519 manufacturing process Methods 0.000 title claims description 8
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical group CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims description 152
- 150000001720 carbohydrates Chemical class 0.000 claims description 138
- 238000000034 method Methods 0.000 claims description 89
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 86
- 102000004169 proteins and genes Human genes 0.000 claims description 69
- 108090000623 proteins and genes Proteins 0.000 claims description 69
- 229920001282 polysaccharide Polymers 0.000 claims description 58
- 239000005017 polysaccharide Substances 0.000 claims description 58
- 150000004676 glycans Chemical class 0.000 claims description 56
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 55
- 150000001718 carbodiimides Chemical class 0.000 claims description 50
- 239000000203 mixture Substances 0.000 claims description 43
- 239000011780 sodium chloride Substances 0.000 claims description 43
- 238000006243 chemical reaction Methods 0.000 claims description 42
- 230000008569 process Effects 0.000 claims description 42
- 238000001914 filtration Methods 0.000 claims description 30
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 29
- 230000021615 conjugation Effects 0.000 claims description 28
- 230000002163 immunogen Effects 0.000 claims description 25
- 125000003277 amino group Chemical group 0.000 claims description 23
- 238000001212 derivatisation Methods 0.000 claims description 22
- 241000606768 Haemophilus influenzae Species 0.000 claims description 13
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
- 241000588650 Neisseria meningitidis Species 0.000 claims description 10
- 230000001580 bacterial effect Effects 0.000 claims description 10
- 241000894006 Bacteria Species 0.000 claims description 9
- 241000293871 Salmonella enterica subsp. enterica serovar Typhi Species 0.000 claims description 9
- 241000191967 Staphylococcus aureus Species 0.000 claims description 8
- 238000009833 condensation Methods 0.000 claims description 8
- 230000005494 condensation Effects 0.000 claims description 8
- 241000607626 Vibrio cholerae Species 0.000 claims description 6
- 201000010099 disease Diseases 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 6
- 238000011282 treatment Methods 0.000 claims description 6
- 229940118696 vibrio cholerae Drugs 0.000 claims description 6
- 241000194017 Streptococcus Species 0.000 claims description 5
- 241000193998 Streptococcus pneumoniae Species 0.000 claims description 5
- 150000001875 compounds Chemical class 0.000 claims description 5
- 239000002158 endotoxin Substances 0.000 claims description 5
- 229920006008 lipopolysaccharide Polymers 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- 229940031000 streptococcus pneumoniae Drugs 0.000 claims description 5
- 241000588724 Escherichia coli Species 0.000 claims description 4
- 241000588655 Moraxella catarrhalis Species 0.000 claims description 4
- 239000012634 fragment Substances 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 4
- 108010071134 CRM197 (non-toxic variant of diphtheria toxin) Proteins 0.000 claims description 3
- 102100037840 Dehydrogenase/reductase SDR family member 2, mitochondrial Human genes 0.000 claims description 3
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 claims description 3
- 241000588677 Neisseria meningitidis serogroup B Species 0.000 claims description 3
- 101710183389 Pneumolysin Proteins 0.000 claims description 3
- 101710188053 Protein D Proteins 0.000 claims description 3
- 101710132893 Resolvase Proteins 0.000 claims description 3
- 241000607142 Salmonella Species 0.000 claims description 3
- 239000007806 chemical reaction intermediate Substances 0.000 claims description 3
- 230000001268 conjugating effect Effects 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 210000002443 helper t lymphocyte Anatomy 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 238000001542 size-exclusion chromatography Methods 0.000 claims description 2
- 125000002843 carboxylic acid group Chemical group 0.000 claims 2
- 241001174901 Neisseria meningitidis alpha275 Species 0.000 claims 1
- 241000921898 Neisseria meningitidis serogroup A Species 0.000 claims 1
- 241000947238 Neisseria meningitidis serogroup C Species 0.000 claims 1
- 239000000243 solution Substances 0.000 description 69
- 229960000814 tetanus toxoid Drugs 0.000 description 69
- 235000018102 proteins Nutrition 0.000 description 52
- 125000006850 spacer group Chemical group 0.000 description 22
- 239000012528 membrane Substances 0.000 description 21
- 238000011026 diafiltration Methods 0.000 description 19
- 230000008878 coupling Effects 0.000 description 17
- 238000010168 coupling process Methods 0.000 description 17
- 238000005859 coupling reaction Methods 0.000 description 17
- 239000003981 vehicle Substances 0.000 description 15
- 230000004075 alteration Effects 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 238000009472 formulation Methods 0.000 description 12
- 230000004044 response Effects 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- 239000012506 Sephacryl® Substances 0.000 description 11
- 108091007433 antigens Proteins 0.000 description 11
- 102000036639 antigens Human genes 0.000 description 11
- 238000000569 multi-angle light scattering Methods 0.000 description 11
- 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 10
- 239000000427 antigen Substances 0.000 description 10
- NHJVRSWLHSJWIN-UHFFFAOYSA-N 2,4,6-trinitrobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O NHJVRSWLHSJWIN-UHFFFAOYSA-N 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 238000002965 ELISA Methods 0.000 description 8
- 238000004132 cross linking Methods 0.000 description 8
- 230000028993 immune response Effects 0.000 description 8
- 230000029219 regulation of pH Effects 0.000 description 8
- -1 1-cyano-4-dimethylamino pyridinium tetrafluoroborate Chemical compound 0.000 description 7
- 101150025437 PSAH gene Proteins 0.000 description 7
- 239000002671 adjuvant Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 108010078791 Carrier Proteins Proteins 0.000 description 6
- 102000014914 Carrier Proteins Human genes 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- 239000004643 cyanate ester Substances 0.000 description 6
- 108090000765 processed proteins & peptides Proteins 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 5
- 108700014070 MenACWY Proteins 0.000 description 5
- 238000006640 acetylation reaction Methods 0.000 description 5
- 230000004913 activation Effects 0.000 description 5
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 5
- 229960003983 diphtheria toxoid Drugs 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- 230000035772 mutation Effects 0.000 description 5
- 230000002572 peristaltic effect Effects 0.000 description 5
- 238000011002 quantification Methods 0.000 description 5
- 230000003612 virological effect Effects 0.000 description 5
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 4
- 201000005702 Pertussis Diseases 0.000 description 4
- 239000007983 Tris buffer Substances 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 239000006227 byproduct Substances 0.000 description 4
- 238000009795 derivation Methods 0.000 description 4
- 229920001542 oligosaccharide Polymers 0.000 description 4
- 150000002482 oligosaccharides Chemical class 0.000 description 4
- 239000012466 permeate Substances 0.000 description 4
- 102000004196 processed proteins & peptides Human genes 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 4
- 238000002255 vaccination Methods 0.000 description 4
- 108010077805 Bacterial Proteins Proteins 0.000 description 3
- 201000005505 Measles Diseases 0.000 description 3
- 208000005647 Mumps Diseases 0.000 description 3
- 210000001744 T-lymphocyte Anatomy 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- IBVAQQYNSHJXBV-UHFFFAOYSA-N adipic acid dihydrazide Chemical compound NNC(=O)CCCCC(=O)NN IBVAQQYNSHJXBV-UHFFFAOYSA-N 0.000 description 3
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 235000018417 cysteine Nutrition 0.000 description 3
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000010348 incorporation Methods 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 208000010805 mumps infectious disease Diseases 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 201000005404 rubella Diseases 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 230000001954 sterilising effect Effects 0.000 description 3
- 238000004659 sterilization and disinfection Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- JWDFQMWEFLOOED-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-(pyridin-2-yldisulfanyl)propanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCSSC1=CC=CC=N1 JWDFQMWEFLOOED-UHFFFAOYSA-N 0.000 description 2
- 108010034055 CRM45 fragment of diphtheria toxin Proteins 0.000 description 2
- 201000006082 Chickenpox Diseases 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- 206010046980 Varicella Diseases 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 2
- ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 description 2
- 239000012736 aqueous medium Substances 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 238000000149 argon plasma sintering Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- SYECJBOWSGTPLU-UHFFFAOYSA-N hexane-1,1-diamine Chemical compound CCCCCC(N)N SYECJBOWSGTPLU-UHFFFAOYSA-N 0.000 description 2
- 238000000265 homogenisation Methods 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine group Chemical group NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- GHMLBKRAJCXXBS-UHFFFAOYSA-N resorcinol Chemical compound OC1=CC=CC(O)=C1 GHMLBKRAJCXXBS-UHFFFAOYSA-N 0.000 description 2
- 239000012465 retentate Substances 0.000 description 2
- 238000005549 size reduction Methods 0.000 description 2
- 241000894007 species Species 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 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
- AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 1
- SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 108010053406 CRM 107 Proteins 0.000 description 1
- 102000009016 Cholera Toxin Human genes 0.000 description 1
- 108010049048 Cholera Toxin Proteins 0.000 description 1
- 241000193163 Clostridioides difficile Species 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 108010053187 Diphtheria Toxin Proteins 0.000 description 1
- 102000016607 Diphtheria Toxin Human genes 0.000 description 1
- 101000597577 Gluconacetobacter diazotrophicus (strain ATCC 49037 / DSM 5601 / CCUG 37298 / CIP 103539 / LMG 7603 / PAl5) Outer membrane protein Proteins 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 101100005713 Homo sapiens CD4 gene Proteins 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-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
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 102000008072 Lymphokines Human genes 0.000 description 1
- 108010074338 Lymphokines Proteins 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 101100173048 Mus musculus Mcat gene Proteins 0.000 description 1
- 206010033078 Otitis media Diseases 0.000 description 1
- 101710116435 Outer membrane protein Proteins 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 239000002262 Schiff base Substances 0.000 description 1
- 150000004753 Schiff bases Chemical class 0.000 description 1
- 101710084578 Short neurotoxin 1 Proteins 0.000 description 1
- 101000874347 Streptococcus agalactiae IgA FC receptor Proteins 0.000 description 1
- 241000193990 Streptococcus sp. 'group B' Species 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 108010055044 Tetanus Toxin Proteins 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
- 101710182223 Toxin B Proteins 0.000 description 1
- 101710182532 Toxin a Proteins 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- UZQJVUCHXGYFLQ-AYDHOLPZSA-N [(2s,3r,4s,5r,6r)-4-[(2s,3r,4s,5r,6r)-4-[(2r,3r,4s,5r,6r)-4-[(2s,3r,4s,5r,6r)-3,5-dihydroxy-6-(hydroxymethyl)-4-[(2s,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,5-dihydroxy-6-(hy Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O)O[C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O)O[C@H]1CC[C@]2(C)[C@H]3CC=C4[C@@]([C@@]3(CC[C@H]2[C@@]1(C=O)C)C)(C)CC(O)[C@]1(CCC(CC14)(C)C)C(=O)O[C@H]1[C@@H]([C@@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O[C@H]4[C@@H]([C@@H](O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O)[C@H](O)[C@@H](CO)O4)O)[C@H](O)[C@@H](CO)O3)O)[C@H](O)[C@@H](CO)O2)O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UZQJVUCHXGYFLQ-AYDHOLPZSA-N 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229960002684 aminocaproic acid Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229920001400 block copolymer Polymers 0.000 description 1
- 229940030156 cell vaccine Drugs 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 238000011210 chromatographic step Methods 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000013461 design 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
- 239000002552 dosage form Substances 0.000 description 1
- 239000012149 elution buffer Substances 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- 229940047650 haemophilus influenzae Drugs 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- SPSXSWRZQFPVTJ-ZQQKUFEYSA-N hepatitis b vaccine Chemical compound C([C@H](NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CCSC)C(=O)N[C@@H](CC1N=CN=C1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)OC(=O)CNC(=O)CNC(=O)[C@H](C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@@H](N)CCCNC(N)=N)C1=CC=CC=C1 SPSXSWRZQFPVTJ-ZQQKUFEYSA-N 0.000 description 1
- 229940124736 hepatitis-B vaccine Drugs 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 230000003308 immunostimulating effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 238000002356 laser light scattering Methods 0.000 description 1
- 150000002632 lipids Chemical group 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 229940035032 monophosphoryl lipid a Drugs 0.000 description 1
- 125000001446 muramyl group Chemical group N[C@@H](C=O)[C@@H](O[C@@H](C(=O)*)C)[C@H](O)[C@H](O)CO 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
- 108010021711 pertactin Proteins 0.000 description 1
- 229920002627 poly(phosphazenes) Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229940023143 protein vaccine Drugs 0.000 description 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 238000003998 size exclusion chromatography high performance liquid chromatography Methods 0.000 description 1
- 238000000527 sonication 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
- 239000003381 stabilizer Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229940118376 tetanus toxin Drugs 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (13)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0513069.5A GB0513069D0 (en) | 2005-06-27 | 2005-06-27 | Immunogenic composition |
| GB0513071 | 2005-06-27 | ||
| GB0513069 | 2005-06-27 | ||
| GBGB0513071.1A GB0513071D0 (en) | 2005-06-27 | 2005-06-27 | Immunogenic composition |
| GB0515556A GB0515556D0 (en) | 2005-07-28 | 2005-07-28 | Immunogenic composition |
| GB0515556 | 2005-07-28 | ||
| GB0524204A GB0524204D0 (en) | 2005-11-28 | 2005-11-28 | Immunogenic composition |
| GB0524204 | 2005-11-28 | ||
| GB0526040 | 2005-12-21 | ||
| GB0526040A GB0526040D0 (en) | 2005-12-21 | 2005-12-21 | Immunogenic composition |
| GB0526041A GB0526041D0 (en) | 2005-12-21 | 2005-12-21 | Immunogenic composition |
| GB0526041 | 2005-12-21 | ||
| PCT/EP2006/006270 WO2007000343A2 (en) | 2005-06-27 | 2006-06-23 | Process for manufacturing vaccines |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| ES2367918T3 ES2367918T3 (es) | 2011-11-10 |
| ES2367918T5 true ES2367918T5 (es) | 2014-11-21 |
Family
ID=34856207
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES06754611.9T Active ES2367918T5 (es) | 2005-06-27 | 2006-06-23 | Procedimiento de fabricación de vacunas |
Country Status (7)
| Country | Link |
|---|---|
| CN (4) | CN101208103B (enExample) |
| ES (1) | ES2367918T5 (enExample) |
| FR (1) | FR12C0060I2 (enExample) |
| GB (1) | GB0513069D0 (enExample) |
| NO (2) | NO2021022I1 (enExample) |
| UA (1) | UA97233C2 (enExample) |
| ZA (3) | ZA200710853B (enExample) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2863178C (en) * | 2012-01-30 | 2021-04-06 | Serum Institute Of India Ltd. | Immunogenic composition |
| IN2015DN00694A (enExample) * | 2012-08-16 | 2015-06-26 | Pfizer | |
| KR20190044663A (ko) * | 2016-09-02 | 2019-04-30 | 사노피 파스퇴르 인크 | 네이세리아 메닌기티디스 백신 |
| MX2019006105A (es) * | 2016-11-25 | 2019-08-21 | Glaxosmithkline Biologicals Sa | Conjugados de vmen-antigeno y uso de los mismos. |
| CN109879967A (zh) * | 2017-12-15 | 2019-06-14 | 苏州和锐生物科技有限公司 | 一种乙酰氨基葡萄糖偶联物的制备方法及应用 |
| CN110251667A (zh) * | 2018-05-11 | 2019-09-20 | 武汉博沃生物科技有限公司 | 一种免疫组合制剂及其制备方法和应用 |
| JP2023503086A (ja) * | 2019-11-22 | 2023-01-26 | グラクソスミスクライン バイオロジカルズ ソシエテ アノニム | 細菌サッカリド複合糖質ワクチンの用法及び用量 |
| CN115819616B (zh) * | 2021-07-28 | 2025-04-11 | 江苏瑞科生物技术股份有限公司 | 一种基因重组vzv融合蛋白及其制备方法和应用 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5180815A (en) * | 1988-04-13 | 1993-01-19 | Fuji Photo Film Co., Ltd. | Modified protein for carrying hapten |
| CZ20024224A3 (cs) * | 2000-06-29 | 2003-05-14 | Glaxosmithkline Biologicals S. A. | Farmaceutický prostředek |
| CN1558773A (zh) * | 2001-04-06 | 2004-12-29 | 巴斯德研究院 | 由与破伤风类毒素结合的霍乱弧菌o139的脂多糖的多糖部分组成的缀合疫苗 |
| GB0115176D0 (en) * | 2001-06-20 | 2001-08-15 | Chiron Spa | Capular polysaccharide solubilisation and combination vaccines |
| CN1401328A (zh) * | 2002-10-18 | 2003-03-12 | 北京绿竹生物技术有限责任公司 | 流行性脑脊髓膜炎多糖－蛋白结合疫苗 |
| PT2172213E (pt) * | 2003-01-30 | 2013-06-03 | Novartis Ag | Vacinas injetáveis contra múltiplos serogrupos meningocócicos |
-
2005
- 2005-06-27 GB GBGB0513069.5A patent/GB0513069D0/en not_active Ceased
-
2006
- 2006-06-23 CN CN2006800233344A patent/CN101208103B/zh active Active
- 2006-06-23 UA UAA200714085A patent/UA97233C2/uk unknown
- 2006-06-23 CN CN2006800311786A patent/CN101247827B/zh active Active
- 2006-06-23 CN CN2006800230577A patent/CN101208101B/zh active Active
- 2006-06-23 CN CN200680023149.5A patent/CN101222935B/zh active Active
- 2006-06-23 ES ES06754611.9T patent/ES2367918T5/es active Active
-
2007
- 2007-12-13 ZA ZA200710853A patent/ZA200710853B/xx unknown
- 2007-12-14 ZA ZA200710909A patent/ZA200710909B/xx unknown
- 2007-12-18 ZA ZA200711074A patent/ZA200711074B/xx unknown
-
2012
- 2012-10-18 FR FR12C0060C patent/FR12C0060I2/fr active Active
-
2021
- 2021-05-25 NO NO2021022C patent/NO2021022I1/no unknown
-
2025
- 2025-04-08 NO NO2025018C patent/NO2025018I1/no unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CN101208101B (zh) | 2013-01-02 |
| UA97233C2 (uk) | 2012-01-25 |
| FR12C0060I2 (fr) | 2017-01-06 |
| CN101247827B (zh) | 2013-07-17 |
| NO2025018I1 (no) | 2025-04-08 |
| NO2021022I1 (no) | 2021-05-25 |
| ZA200710909B (en) | 2009-04-29 |
| CN101208103A (zh) | 2008-06-25 |
| CN101208101A (zh) | 2008-06-25 |
| ZA200710853B (en) | 2009-04-29 |
| FR12C0060I1 (enExample) | 2012-12-14 |
| CN101222935B (zh) | 2015-07-29 |
| CN101247827A (zh) | 2008-08-20 |
| CN101208103B (zh) | 2013-04-24 |
| CN101222935A (zh) | 2008-07-16 |
| ES2367918T3 (es) | 2011-11-10 |
| GB0513069D0 (en) | 2005-08-03 |
| ZA200711074B (en) | 2009-07-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2621780T3 (es) | Procedimiento de fabricación de vacunas | |
| CN110859957B (zh) | 包含缀合荚膜糖抗原的免疫原性组合物及其用途 | |
| US20090311285A1 (en) | Vaccine | |
| ES2367918T5 (es) | Procedimiento de fabricación de vacunas | |
| RU2827429C1 (ru) | Иммуногенные композиции для применения в пневмококковых вакцинах | |
| HK1153679A (en) | Process for manufacturing vaccines | |
| HK1114011B (en) | Process for manufacturing vaccines | |
| HK1114011C (en) | Process for manufacturing vaccines |