WO1993013797B1 - Vaccin conjugue a base de toxine du cholera et de lypopolysaccharide (lps) detoxique, utilise pour la prevention du cholera - Google Patents
Vaccin conjugue a base de toxine du cholera et de lypopolysaccharide (lps) detoxique, utilise pour la prevention du choleraInfo
- Publication number
- WO1993013797B1 WO1993013797B1 PCT/US1993/000253 US9300253W WO9313797B1 WO 1993013797 B1 WO1993013797 B1 WO 1993013797B1 US 9300253 W US9300253 W US 9300253W WO 9313797 B1 WO9313797 B1 WO 9313797B1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- lipopolysaccharide
- cholera
- vaccine
- detoxified
- protein carrier
- Prior art date
Links
- 206010008631 Cholera Diseases 0.000 title claims 10
- 230000002265 prevention Effects 0.000 title claims 3
- 108010060123 Conjugate Vaccines Proteins 0.000 title 1
- 229940031670 conjugate vaccine Drugs 0.000 title 1
- 239000002596 immunotoxin Substances 0.000 title 1
- 229960005486 vaccine Drugs 0.000 claims abstract 23
- 241000607626 Vibrio cholerae Species 0.000 claims abstract 18
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims abstract 14
- 102000004169 proteins and genes Human genes 0.000 claims abstract 9
- 108090000623 proteins and genes Proteins 0.000 claims abstract 9
- 102000009016 Cholera Toxin Human genes 0.000 claims abstract 5
- 108010049048 Cholera Toxin Proteins 0.000 claims abstract 5
- 229960005004 cholera vaccine Drugs 0.000 claims abstract 3
- 239000000203 mixture Substances 0.000 claims abstract 2
- 230000002850 vibriocidal effect Effects 0.000 claims abstract 2
- 239000002158 endotoxin Substances 0.000 claims 17
- 229920006008 lipopolysaccharide Polymers 0.000 claims 17
- 238000000034 method Methods 0.000 claims 12
- 125000002252 acyl group Chemical group 0.000 claims 4
- 230000001588 bifunctional effect Effects 0.000 claims 4
- 235000014113 dietary fatty acids Nutrition 0.000 claims 4
- 239000003814 drug Substances 0.000 claims 4
- 229930195729 fatty acid Natural products 0.000 claims 4
- 239000000194 fatty acid Substances 0.000 claims 4
- 150000004665 fatty acids Chemical class 0.000 claims 4
- 230000003053 immunization Effects 0.000 claims 4
- GZQKNULLWNGMCW-PWQABINMSA-N lipid A (E. coli) Chemical compound O1[C@H](CO)[C@@H](OP(O)(O)=O)[C@H](OC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCCCC)[C@@H](NC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCC)[C@@H]1OC[C@@H]1[C@@H](O)[C@H](OC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](NC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](OP(O)(O)=O)O1 GZQKNULLWNGMCW-PWQABINMSA-N 0.000 claims 4
- 238000004519 manufacturing process Methods 0.000 claims 4
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims 2
- 229940032024 DPT vaccine Drugs 0.000 claims 2
- 201000005702 Pertussis Diseases 0.000 claims 2
- 150000008065 acid anhydrides Chemical class 0.000 claims 2
- 230000001580 bacterial effect Effects 0.000 claims 2
- 238000006243 chemical reaction Methods 0.000 claims 2
- 239000003153 chemical reaction reagent Substances 0.000 claims 2
- 206010013023 diphtheria Diseases 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 2
- 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 claims 2
- 229940124736 hepatitis-B vaccine Drugs 0.000 claims 2
- 244000005700 microbiome Species 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 230000001681 protective effect Effects 0.000 claims 2
- 229960000814 tetanus toxoid Drugs 0.000 claims 2
- JWDFQMWEFLOOED-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-(pyridin-2-yldisulfanyl)propanoate Chemical group O=C1CCC(=O)N1OC(=O)CCSSC1=CC=CC=N1 JWDFQMWEFLOOED-UHFFFAOYSA-N 0.000 claims 1
- 231100000699 Bacterial toxin Toxicity 0.000 claims 1
- 241000124008 Mammalia Species 0.000 claims 1
- 241000607598 Vibrio Species 0.000 claims 1
- IBVAQQYNSHJXBV-UHFFFAOYSA-N adipic acid dihydrazide Chemical compound NNC(=O)CCCCC(=O)NN IBVAQQYNSHJXBV-UHFFFAOYSA-N 0.000 claims 1
- 239000000688 bacterial toxin Substances 0.000 claims 1
- 230000001419 dependent effect Effects 0.000 claims 1
- NAQMVNRVTILPCV-UHFFFAOYSA-N hexane-1,6-diamine Chemical compound NCCCCCCN NAQMVNRVTILPCV-UHFFFAOYSA-N 0.000 claims 1
- 238000002649 immunization Methods 0.000 claims 1
- 238000001556 precipitation Methods 0.000 claims 1
- 238000000746 purification Methods 0.000 claims 1
- 239000003053 toxin Substances 0.000 claims 1
- 231100000765 toxin Toxicity 0.000 claims 1
- 241000699802 Cricetulus griseus Species 0.000 abstract 1
- 241000699670 Mus sp. Species 0.000 abstract 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 abstract 1
- 238000005903 acid hydrolysis reaction Methods 0.000 abstract 1
- 230000000890 antigenic effect Effects 0.000 abstract 1
- 150000001720 carbohydrates Chemical class 0.000 abstract 1
- 229940030156 cell vaccine Drugs 0.000 abstract 1
- 230000002346 endotoxic effect Effects 0.000 abstract 1
- 238000009472 formulation Methods 0.000 abstract 1
- 230000001900 immune effect Effects 0.000 abstract 1
- 239000002510 pyrogen Substances 0.000 abstract 1
- 239000011780 sodium chloride Substances 0.000 abstract 1
- 230000002588 toxic effect Effects 0.000 abstract 1
Abstract
L'invention décrit une formulation de vaccin comprenant des conjugués composés de LPS détoxiqués et de protéines comprenant la toxine du choléra (CT). Le traitement à l'aide de l'hydrazine (DeA-LPS) réduit les caractéristiques endotoxiques du LPS à des niveaux admissibles, et produit une molécule plus importante, et à activité/antigénique accrue, par rapport au saccharide produit par hydrolyse acide. Des conjugués utilisant la toxine de V. cholerae sont également décrit, lesquels présentent de faibles niveaux de pyrogènes, aucune activité toxique par rapport aux cellules ovariennes du hamster chinois, et induisent des réponses de renforcement chez les anticorps vibriocides et les anticorps dirigés contre la toxine du choléra lorsqu'ils sont injectés par voie sous-cutanée sous forme de solutions salines dans des souris. Les conjuguées produits sous forme de vaccin contre le choléra induisent la formation des mêmes anticorps que les vaccins cellulaires à injection parentérale, mais présentent des caractéristiques immunologiques et une sécurité améliorées.
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU34696/93A AU678549B2 (en) | 1992-01-16 | 1993-01-14 | Detoxified LPS-cholera toxin conjugate vaccine for prevention of cholera |
| EP93903428A EP0623026A1 (fr) | 1992-01-16 | 1993-01-14 | Vaccin conjugue a base de toxine du cholera et de lypopolysaccharide (lps) detoxique, utilise pour la prevention du cholera |
| JP5512624A JPH07503238A (ja) | 1992-01-16 | 1993-01-14 | コレラ予防用の無毒化ｌｐｓ−コレラ毒素結合ワクチン |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US82145392A | 1992-01-16 | 1992-01-16 | |
| US07/821,453 | 1992-01-16 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| WO1993013797A2 WO1993013797A2 (fr) | 1993-07-22 |
| WO1993013797A3 WO1993013797A3 (fr) | 1993-10-28 |
| WO1993013797B1 true WO1993013797B1 (fr) | 1994-01-20 |
Family
ID=25233450
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1993/000253 WO1993013797A2 (fr) | 1992-01-16 | 1993-01-14 | Vaccin conjugue a base de toxine du cholera et de lypopolysaccharide (lps) detoxique, utilise pour la prevention du cholera |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP0623026A1 (fr) |
| JP (1) | JPH07503238A (fr) |
| AU (1) | AU678549B2 (fr) |
| CA (1) | CA2128212A1 (fr) |
| WO (1) | WO1993013797A2 (fr) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU1420897A (en) * | 1996-12-18 | 1998-07-15 | Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services, The | Conjugate vaccine for (salmonella paratyphi) a |
| US6531131B1 (en) | 1999-08-10 | 2003-03-11 | The United States Of America As Represented By The Department Of Health And Human Services | Conjugate vaccine for Neisseria meningitidis |
| AU2001253568A1 (en) | 2000-04-18 | 2001-10-30 | Dan C. Deborde | Lipopolysaccharide-conjugate vaccine for sepsis treatment |
| US7749511B2 (en) | 2000-04-18 | 2010-07-06 | Endobiologics, Incorporated | Anti-sepsis conjugate vaccine |
| US7527797B1 (en) * | 2000-09-01 | 2009-05-05 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Vibrio cholerae 0139 conjugate vaccines |
| WO2002080964A1 (fr) * | 2001-04-06 | 2002-10-17 | Institut Pasteur | Vaccin conjugue d'un fragment de polysaccharide de lipopolysaccharide du vibrio cholerae 0139 lie a l'anatoxine tetanique |
| WO2003094961A1 (fr) | 2002-05-09 | 2003-11-20 | Massimo Porro | Vaccins de polysaccharides et de glycoconjugues ameliores |
| BR0316271A (pt) * | 2002-11-14 | 2005-10-11 | Inst Finlay Ct De Investigacio | Método para a obtenção de preparados vacinais conjugados multivalentes, composição vacinal multivalente e uso da mesma |
| US8048432B2 (en) | 2003-08-06 | 2011-11-01 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Polysaccharide-protein conjugate vaccines |
| CN102824632A (zh) * | 2012-09-12 | 2012-12-19 | 北京民海生物科技有限公司 | 霍乱弧菌o1群多糖结合疫苗、其制备方法及应用 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2532850B1 (fr) * | 1982-09-15 | 1985-12-20 | Pasteur Institut | Conjugues immunogenes entre un haptene et une molecule porteuse derivee d'une toxine, les vaccins les composant et procede pour leur obtention |
| US4663160A (en) * | 1983-03-14 | 1987-05-05 | Miles Laboratories, Inc. | Vaccines for gram-negative bacteria |
-
1993
- 1993-01-14 CA CA002128212A patent/CA2128212A1/fr not_active Abandoned
- 1993-01-14 WO PCT/US1993/000253 patent/WO1993013797A2/fr not_active Application Discontinuation
- 1993-01-14 AU AU34696/93A patent/AU678549B2/en not_active Ceased
- 1993-01-14 JP JP5512624A patent/JPH07503238A/ja active Pending
- 1993-01-14 EP EP93903428A patent/EP0623026A1/fr not_active Withdrawn
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