CA2224052C - Proteine de la membrane externe de bordetella pertussis - Google Patents
Proteine de la membrane externe de bordetella pertussis Download PDFInfo
- Publication number
- CA2224052C CA2224052C CA002224052A CA2224052A CA2224052C CA 2224052 C CA2224052 C CA 2224052C CA 002224052 A CA002224052 A CA 002224052A CA 2224052 A CA2224052 A CA 2224052A CA 2224052 C CA2224052 C CA 2224052C
- Authority
- CA
- Canada
- Prior art keywords
- pertactin
- component
- purified
- solution
- pertussis
- 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.)
- Expired - Lifetime
Links
- 201000005702 Pertussis Diseases 0.000 title description 17
- 101710116435 Outer membrane protein Proteins 0.000 title description 5
- 108010021711 pertactin Proteins 0.000 claims abstract description 120
- 108010081690 Pertussis Toxin Proteins 0.000 claims abstract description 37
- 241000588832 Bordetella pertussis Species 0.000 claims abstract description 33
- 229910052588 hydroxylapatite Inorganic materials 0.000 claims abstract description 19
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 claims abstract description 19
- 239000012614 Q-Sepharose Substances 0.000 claims abstract description 18
- 102000030621 adenylate cyclase Human genes 0.000 claims abstract description 16
- 108060000200 adenylate cyclase Proteins 0.000 claims abstract description 16
- 230000000694 effects Effects 0.000 claims abstract description 15
- 238000000855 fermentation Methods 0.000 claims abstract description 15
- 230000004151 fermentation Effects 0.000 claims abstract description 15
- 229960005486 vaccine Drugs 0.000 claims description 43
- 239000000243 solution Substances 0.000 claims description 33
- 102000036639 antigens Human genes 0.000 claims description 32
- 108091007433 antigens Proteins 0.000 claims description 32
- 239000000427 antigen Substances 0.000 claims description 31
- 238000000034 method Methods 0.000 claims description 25
- 239000007864 aqueous solution Substances 0.000 claims description 11
- 238000004587 chromatography analysis Methods 0.000 claims description 11
- 239000000463 material Substances 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 239000011159 matrix material Substances 0.000 claims description 7
- 238000005342 ion exchange Methods 0.000 claims description 5
- 241000588807 Bordetella Species 0.000 claims description 4
- 238000011403 purification operation Methods 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 3
- 230000006872 improvement Effects 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- 229960000814 tetanus toxoid Drugs 0.000 claims description 3
- 239000000356 contaminant Substances 0.000 claims description 2
- 229960003983 diphtheria toxoid Drugs 0.000 claims description 2
- 238000011109 contamination Methods 0.000 claims 2
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 abstract description 21
- 229910052921 ammonium sulfate Inorganic materials 0.000 abstract description 20
- 239000001166 ammonium sulphate Substances 0.000 abstract description 20
- 235000011130 ammonium sulphate Nutrition 0.000 abstract description 20
- 239000002244 precipitate Substances 0.000 abstract description 10
- 239000000872 buffer Substances 0.000 abstract description 8
- 238000000108 ultra-filtration Methods 0.000 abstract description 8
- 239000000284 extract Substances 0.000 abstract description 7
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 abstract description 4
- 239000004202 carbamide Substances 0.000 abstract description 4
- 101710118506 69 kDa protein Proteins 0.000 abstract description 2
- 210000004027 cell Anatomy 0.000 description 20
- 235000018102 proteins Nutrition 0.000 description 19
- 102000004169 proteins and genes Human genes 0.000 description 19
- 108090000623 proteins and genes Proteins 0.000 description 19
- 235000010633 broth Nutrition 0.000 description 18
- 239000012528 membrane Substances 0.000 description 18
- 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 14
- 239000000203 mixture Substances 0.000 description 10
- ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 description 9
- 229940001007 aluminium phosphate Drugs 0.000 description 9
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 9
- 238000005119 centrifugation Methods 0.000 description 9
- 201000010099 disease Diseases 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 239000010451 perlite Substances 0.000 description 8
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- 238000000746 purification Methods 0.000 description 8
- 238000002965 ELISA Methods 0.000 description 7
- 208000015181 infectious disease Diseases 0.000 description 7
- 239000006228 supernatant Substances 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
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- 239000002953 phosphate buffered saline Substances 0.000 description 5
- 238000001556 precipitation Methods 0.000 description 5
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- 239000003755 preservative agent Substances 0.000 description 5
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- 235000019624 protein content Nutrition 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- QCDWFXQBSFUVSP-UHFFFAOYSA-N 2-phenoxyethanol Chemical compound OCCOC1=CC=CC=C1 QCDWFXQBSFUVSP-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 239000012736 aqueous medium Substances 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 230000003053 immunization Effects 0.000 description 3
- 238000002649 immunization Methods 0.000 description 3
- 230000005847 immunogenicity Effects 0.000 description 3
- 238000011031 large-scale manufacturing process Methods 0.000 description 3
- 229940066827 pertussis vaccine Drugs 0.000 description 3
- 229960005323 phenoxyethanol Drugs 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 241000588779 Bordetella bronchiseptica Species 0.000 description 2
- 241000700198 Cavia Species 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 239000003463 adsorbent Substances 0.000 description 2
- 230000005875 antibody response Effects 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000005194 fractionation Methods 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 238000001155 isoelectric focusing Methods 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 239000012465 retentate Substances 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 2
- 229940033663 thimerosal Drugs 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 241000588780 Bordetella parapertussis Species 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 206010011469 Crying Diseases 0.000 description 1
- 206010011878 Deafness Diseases 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- 206010024769 Local reaction Diseases 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- 101710160107 Outer membrane protein A Proteins 0.000 description 1
- 101710194807 Protective antigen Proteins 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000005571 anion exchange chromatography Methods 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000001045 blue dye Substances 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229960002713 calcium chloride Drugs 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 229940030156 cell vaccine Drugs 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000013043 chemical agent Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 229960002433 cysteine Drugs 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000011026 diafiltration Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 235000003891 ferrous sulphate Nutrition 0.000 description 1
- 239000011790 ferrous sulphate Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 235000003969 glutathione Nutrition 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 229920006008 lipopolysaccharide Polymers 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000005374 membrane filtration Methods 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 238000001471 micro-filtration Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- LPUQAYUQRXPFSQ-DFWYDOINSA-M monosodium L-glutamate Chemical compound [Na+].[O-]C(=O)[C@@H](N)CCC(O)=O LPUQAYUQRXPFSQ-DFWYDOINSA-M 0.000 description 1
- 235000013923 monosodium glutamate Nutrition 0.000 description 1
- 239000004223 monosodium glutamate Substances 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 230000031787 nutrient reservoir activity Effects 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 230000001698 pyrogenic effect Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 230000001018 virulence Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Landscapes
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA002359307A CA2359307A1 (fr) | 1990-04-04 | 1991-04-03 | Proteine de la membrane externe de bordetella pertussis |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB909007656A GB9007656D0 (en) | 1989-04-04 | 1990-04-04 | Control system |
| GB9007656.1 | 1990-04-04 | ||
| CA002079887A CA2079887C (fr) | 1990-04-04 | 1991-04-03 | Purification d'une proteine de membrane externe de la coqueluche |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002079887A Division CA2079887C (fr) | 1990-04-04 | 1991-04-03 | Purification d'une proteine de membrane externe de la coqueluche |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002359307A Division CA2359307A1 (fr) | 1990-04-04 | 1991-04-03 | Proteine de la membrane externe de bordetella pertussis |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2224052A1 CA2224052A1 (fr) | 1991-10-05 |
| CA2224052C true CA2224052C (fr) | 2001-12-18 |
Family
ID=25675568
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002224052A Expired - Lifetime CA2224052C (fr) | 1990-04-04 | 1991-04-03 | Proteine de la membrane externe de bordetella pertussis |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2224052C (fr) |
-
1991
- 1991-04-03 CA CA002224052A patent/CA2224052C/fr not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| CA2224052A1 (fr) | 1991-10-05 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKEX | Expiry |