DE3781541T2 - Modifiziertes pertussistoxin. - Google Patents
Modifiziertes pertussistoxin.Info
- Publication number
- DE3781541T2 DE3781541T2 DE8787311279T DE3781541T DE3781541T2 DE 3781541 T2 DE3781541 T2 DE 3781541T2 DE 8787311279 T DE8787311279 T DE 8787311279T DE 3781541 T DE3781541 T DE 3781541T DE 3781541 T2 DE3781541 T2 DE 3781541T2
- Authority
- DE
- Germany
- Prior art keywords
- subunit
- pertussis
- holotoxin
- toxin
- ptx
- 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.)
- Revoked
Links
- 108010081690 Pertussis Toxin Proteins 0.000 title claims abstract description 54
- 241000588832 Bordetella pertussis Species 0.000 claims abstract description 81
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- 239000003053 toxin Substances 0.000 claims description 22
- 231100000765 toxin Toxicity 0.000 claims description 22
- 238000000034 method Methods 0.000 claims description 18
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- 150000001413 amino acids Chemical class 0.000 claims description 7
- 230000005847 immunogenicity Effects 0.000 claims description 6
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Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/235—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Bordetella (G)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- Medicinal Chemistry (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Biophysics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Physics & Mathematics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Plant Pathology (AREA)
- General Chemical & Material Sciences (AREA)
- Microbiology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Pharmacology & Pharmacy (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Claims (12)
1. Genetische Information umfassende Nukleotidsequenz, die für die aus
Bordetella pertussis isolierte S1-Untereinheit von Pertussistoxinprotein
kodiert, worin die Sequenz modifiziert worden ist, um für eine mutierte
S1-Untereinheit von Pertussistoxin zu kodieren, wobei die genannte mutierte
S1-Untereinheit zur Interaktion mit Pertussistoxin B-Untereinheit fähig ist,
um ein Holotoxin zu bilden, welchem Holotoxin die Toxizität von
Wildtyp-Pertussistoxin fehlt, welches aber schützende Immunogenität aufweist.
2. Sequenz nach Anspruch 1, worin 3x Nukleotide in ein für S1 kodierendes
Segment des genannten Toxins eingefügt sind, worin x eine ganze Zahl von 1
bis 20 ist.
3. Sequenz nach Anspruch 2, worin die genannten Nukleotide in die SalI-Stelle
des offenen Leserasters der S1-Untereinheit eingefügt sind.
4. Sequenz nach Anspruch 2 oder 3, worin die Einfügung zwölf Nukleotide umfaßt,
die für die Aminosäuren Val-Asp-Gly-Ser kodieren.
5. Sequenz nach Anspruch 1, worin die modifizierte genetische Information
eine oder mehrere spezifische Mutationen in der für die S1-Untereinheit
kodierenden Sequenz umfaßt, worin jede derartige spezifische Mutation zu einer
Änderung in einer Aminosäure führt.
6. Polypeptid bestehend aus einer Sequenz von Aminosäuren, worin das genannte
Polypeptid eine mutierte S1-Untereinheit ist, für welche die Nukleotidsequenz
nach einem der Ansprüche 1 bis 5 kodiert, die bei der Interaktion mit
Pertussistoxin B-Untereinheit ein Holotoxin bildet, welchem Holotoxin die
Toxizität von Wildtyp-Pertussistoxin fehlt, welches aber schützende
Immunogenität aufweist.
7. Pertussisholotoxin, umfassend eine B-Untereinheit von Pertussistoxin und
eine mutierte S1-Untereinheit, welchem Holotoxin die Toxizität von
Wildtyp-Pertussistoxin fehlt, welches aber schützende Immunogenität aufweist.
8. Holotoxin nach Anspruch 7, worin die mutierte S1-Untereinheit eine solche
nach Anspruch 6 ist.
9. Holotoxin nach Anspruch 7 oder 8, worin die genannte mutierte
S1-Untereinheit ptx3201 umfaßt, wie in Fig. 4 gezeigt.
10. Verfahren zum Erzeugen einer mutierten S1-Untereinheit eines
Pertussisholotoxins, das zur Interaktion mit Pertussis B-Unterheit fähig ist,
um ein Holotoxin zu bilden, welchem Holotoxin die Virulenz von
Wildtyp-Pertussistoxin fehlt, das aber zur Immunogenität fähig ist, wobei
das genannte Verfahren umfaßt:
Kultivieren eines Bordetella pertussis-Stammes, der modifiziert wurde, um
einen tac-Promotor zu enthalten, der operabel stromaufwärts vom genannten
Untereinheitgen eingefügt ist, wodurch die genannte Untereinheit konstitutiv
exprimiert wird, und Isolieren der genannten Untereinheit vom genannten
Kulturmedium.
11. Verfahren nach Anspruch 10, worin die genannte mutierte S1-Untereinheit
eine Einfügung von 1 bis 20 Aminosäuren aufweist.
12. Verfahren nach Anspruch 10 oder 11, worin die genannte mutierte
S1-Untereinheit ptx3201 umfaßt, wie in Fig. 4 gezeigt.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US94583286A | 1986-12-23 | 1986-12-23 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE3781541D1 DE3781541D1 (de) | 1992-10-08 |
| DE3781541T2 true DE3781541T2 (de) | 1993-05-06 |
Family
ID=25483606
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE8787311279T Revoked DE3781541T2 (de) | 1986-12-23 | 1987-12-22 | Modifiziertes pertussistoxin. |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP0275689B1 (de) |
| JP (1) | JP2867374B2 (de) |
| AT (1) | ATE80179T1 (de) |
| DE (1) | DE3781541T2 (de) |
| ES (1) | ES2044959T3 (de) |
| GR (1) | GR3006444T3 (de) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1202612B (it) * | 1987-03-03 | 1989-02-09 | Eniricerche Spa | Plasmidi ricombinanti utili per l'espressione in bacillus di proteine eterologhe |
| KR0168039B1 (ko) * | 1987-09-04 | 1999-01-15 | 로버트 디. 웨스트 | 재조합 dna에서 유도한 보르데텔라 외독소 소단위체의 유사체 및 그를 포함하는 백신 |
| IT1223334B (it) * | 1987-11-02 | 1990-09-19 | Sclavo Spa | Polipeptidi immunologicamente attivi con una tossicita' alterata utili per la preparazione di un vaccino antipertosse |
| US5244657A (en) * | 1987-11-24 | 1993-09-14 | Connaught Laboratories Limited | Genetic detoxification of pertussis toxin |
| GB8727489D0 (en) * | 1987-11-24 | 1987-12-23 | Connaught Lab | Detoxification of pertussis toxin |
| US5332583A (en) * | 1987-11-24 | 1994-07-26 | Connaught Laboratories Limited | Vaccine containing genetically-detoxified pertussis holotoxin |
| US5358868A (en) * | 1987-11-24 | 1994-10-25 | Connaught Laboratories Limited | Genetic detoxification of pertussis toxin |
| FR2638169B1 (fr) * | 1988-10-25 | 1991-01-11 | Pasteur Institut | Derives d'adenyl cyclase et leurs utilisations biologiques |
| US5786189A (en) * | 1989-11-29 | 1998-07-28 | Smithkline Beecham Biologicals (S.A.) | Vaccine |
| FR2736064B1 (fr) | 1995-06-30 | 1997-09-05 | Pasteur Institut | Epitopes protecteurs de l'adenyl cyclase-hemolysine(ac-hty). leur application au traitement ou a la prevention des infections par bordetella |
| GB0313916D0 (en) | 2003-06-16 | 2003-07-23 | Glaxosmithkline Biolog Sa | Vaccine composition |
| US20140037680A1 (en) | 2012-08-06 | 2014-02-06 | Glaxosmithkline Biologicals, S.A. | Novel method |
| AU2013301312A1 (en) | 2012-08-06 | 2015-03-19 | Glaxosmithkline Biologicals S.A. | Method for eliciting in infants an immune response against RSV and B. pertussis |
| US8916173B2 (en) | 2013-03-08 | 2014-12-23 | Crucell Holland B.V. | Acellular pertussis vaccine |
| KR20160040290A (ko) | 2013-08-05 | 2016-04-12 | 글락소스미스클라인 바이오로지칼즈 에스.에이. | 조합 면역원성 조성물 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS58146596A (ja) * | 1982-02-25 | 1983-09-01 | Takeda Chem Ind Ltd | 組換えｄｎａ、それで形質転換させた微生物およびそれらの用途 |
| GB8333131D0 (en) * | 1983-12-12 | 1984-01-18 | Glaxo Group Ltd | Microbiological process |
| FR2590483B1 (fr) * | 1985-11-22 | 1988-12-09 | Pasteur Institut | Antigenes purifies ayant des proprietes vaccinantes contre b. pertussis, moyens notamment adns recombinants pour les produire et compositions de vaccins les contenant |
| CA1340373C (en) * | 1986-01-28 | 1999-02-02 | Rino Rappuoli | Cloning and sequencing of the dna fragment which codes for the five subunits of the pertussis toxin, a hybrid plasmid containing the dna fragment and micro-organisms transformed by the hybrid plasmid and capable of expressing all or some of the subunits of the pertussis toxin |
| US4883761A (en) * | 1986-03-25 | 1989-11-28 | The United States Of America As Represented By The Department Of Health And Human Services | Pertussis toxin gene: cloning and expression of protective antigen |
-
1987
- 1987-12-22 ES ES87311279T patent/ES2044959T3/es not_active Expired - Lifetime
- 1987-12-22 DE DE8787311279T patent/DE3781541T2/de not_active Revoked
- 1987-12-22 EP EP87311279A patent/EP0275689B1/de not_active Expired - Lifetime
- 1987-12-22 AT AT87311279T patent/ATE80179T1/de active
- 1987-12-23 JP JP62324175A patent/JP2867374B2/ja not_active Expired - Lifetime
-
1992
- 1992-12-02 GR GR920402808T patent/GR3006444T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| GR3006444T3 (de) | 1993-06-21 |
| JPS63240789A (ja) | 1988-10-06 |
| JP2867374B2 (ja) | 1999-03-08 |
| EP0275689A1 (de) | 1988-07-27 |
| EP0275689B1 (de) | 1992-09-02 |
| ES2044959T3 (es) | 1994-01-16 |
| ATE80179T1 (de) | 1992-09-15 |
| DE3781541D1 (de) | 1992-10-08 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8363 | Opposition against the patent | ||
| 8331 | Complete revocation |