CA2413546A1 - Modification of hepatitis b core antigen - Google Patents
Modification of hepatitis b core antigen Download PDFInfo
- Publication number
- CA2413546A1 CA2413546A1 CA002413546A CA2413546A CA2413546A1 CA 2413546 A1 CA2413546 A1 CA 2413546A1 CA 002413546 A CA002413546 A CA 002413546A CA 2413546 A CA2413546 A CA 2413546A CA 2413546 A1 CA2413546 A1 CA 2413546A1
- Authority
- CA
- Canada
- Prior art keywords
- protein
- hbcag
- epitope
- terminal
- sequence
- 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.)
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
-
- 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
- A61K2039/525—Virus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- 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
- C12N2730/00—Reverse transcribing DNA viruses
- C12N2730/00011—Details
- C12N2730/10011—Hepadnaviridae
- C12N2730/10111—Orthohepadnavirus, e.g. hepatitis B virus
- C12N2730/10122—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
-
- 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
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Virology (AREA)
- General Health & Medical Sciences (AREA)
- Gastroenterology & Hepatology (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Genetics & Genomics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Biotechnology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
A protein is provided comprising hepatitis B core antigen (HBcAg) wherein one or more of the four arginine repeats has been deleted, said protein comprising the C-terminal cysteine of HBcAg. The deleted region may be replaced by an epitope from a protein other than HBcAg, in which case the HBcAg acts as a carrier to present the epitope to the immune system. The chimeric protein is useful in prophylactic and therapeutic vaccination of a host, for example against hepatitis B virus.
Claims (27)
1. A protein comprising hepatitis B core antigen (HBcAg) wherein one or more of th_ four arginine repeats is absent and a C-terminal cysteine residue is present.
2. A protein according to claim 1 wherein a first epitope from a protein other than HBcAg is present in place of the absent arginine repeat(s).
3. A protein according to claim 1 or 2 wherein the first arginine repeat is present and the second to fourth arginine repeats are absent.
4. A protein according to any one of the preceding claims wherein a sequence lying between residues 145 and 182 of HBcAg is absent.
5. A protein according to any one of the preceding claims wherein a sequence lying between residues 150 and 177 of HBcAg is absent.
6. A protein according to any one of the preceding claims which comprises a second epitope from a protein other than HBcAg, the second epitope being in the e1 loop.
7. A protein according to claim 6 wherein the second epitope is a B-cell epitope.
8. A protein according to any one of claims 2 to 7 wherein the first epitope is a T-cell epitope.
9. A protein according to claim 8 wherein the first epitope is a T-helper cell epitope and the second epitope is a B-cell epitope.
10. A protein according to claim 6 which comprises said first and second epitopes wherein the epitopes are the same.
11. A protein according to any one of claims 2 to 10 wherein the first and/or the second epitope is from hepatitis B virus (HBV).
12. A protein according to claim 11 wherein the first and/or the second epitope is from the pre-S1, pre-S2 or S region of HBV.
13. A protein according to claim 1 comprising the following elements linked in an N-terminal to C-terminal direction:
(i) an N-terminal part of HBcAg which mediates the formation of particles, and (ii) a C-terminal part of HBcAg comprising the C-terminal cysteine;
.
wherein at least a part of the sequence of HBcAg from between said N-terminal part and said C-terminal part comprising one or more of the arginine repeats is absent.
(i) an N-terminal part of HBcAg which mediates the formation of particles, and (ii) a C-terminal part of HBcAg comprising the C-terminal cysteine;
.
wherein at least a part of the sequence of HBcAg from between said N-terminal part and said C-terminal part comprising one or more of the arginine repeats is absent.
14. A protein according to claim 1 comprising the following elements linked in an N-to C-terminal direction:
(i) an N-terminal part of HBcAg which mediates the formation of particles, (ii) an epitope from a protein other than HBcAg, and (iii) a C-terminal part of HBcAg comprising the C-terminal cysteine;
wherein at least a part of the sequence of HBcAg between said N-terminal part and said C-terminal part comprising one or more of the arginine repeats is absent and is replaced by said epitope.
(i) an N-terminal part of HBcAg which mediates the formation of particles, (ii) an epitope from a protein other than HBcAg, and (iii) a C-terminal part of HBcAg comprising the C-terminal cysteine;
wherein at least a part of the sequence of HBcAg between said N-terminal part and said C-terminal part comprising one or more of the arginine repeats is absent and is replaced by said epitope.
15. A protein according to claim 1 comprising the following elements linked in an N-to C-terminal direction:
(i) an N-terminal part of the HBcAg sequence comprising residues 1 to 67, (ii) an epitope from a protein other than HBcAg, (iii) a second part of the HBcAg sequence comprising residues 91 to 144, and (iv) a third part of the HBcAg sequence comprising the C-terminal cysteine;
wherein at least a part of the sequence of HBcAg from between residue 145 and the C-terminal cysteine comprising one or more of the arginine repeats is absent.
(i) an N-terminal part of the HBcAg sequence comprising residues 1 to 67, (ii) an epitope from a protein other than HBcAg, (iii) a second part of the HBcAg sequence comprising residues 91 to 144, and (iv) a third part of the HBcAg sequence comprising the C-terminal cysteine;
wherein at least a part of the sequence of HBcAg from between residue 145 and the C-terminal cysteine comprising one or more of the arginine repeats is absent.
16. A protein according to claim 1 comprising the following elements linked in an N-to C-terminal direction:
(i) an N-terminal part of the HBcAg sequence comprising residues 1 to 67;
(ii) an epitope from a protein other than HBcAg, (iii) a second part of the HBcAg sequence comprising residues 91 to 144;
(iv) a further epitope from a protein other than HBcAg;
(v) a third part of the HBcAg sequence comprising the C-terminal cysteine;
wherein at least a part of the sequence of HBcAg from between residue 145 and the C-terminal cysteine comprising one or more of the arginine repeats is absent.
(i) an N-terminal part of the HBcAg sequence comprising residues 1 to 67;
(ii) an epitope from a protein other than HBcAg, (iii) a second part of the HBcAg sequence comprising residues 91 to 144;
(iv) a further epitope from a protein other than HBcAg;
(v) a third part of the HBcAg sequence comprising the C-terminal cysteine;
wherein at least a part of the sequence of HBcAg from between residue 145 and the C-terminal cysteine comprising one or more of the arginine repeats is absent.
17. A particle comprising multiple copies of a protein as claimed in any one of the preceding claims.
18. A nucleic acid molecule encoding a protein as claimed in any one of claims 1 to 16.
19. A nucleic acid molecule according to claim 18 which is an expression vector.
20. A host cell transformed or transfected with a nucleic acid molecule as claimed in claim 18 or 19.
21. A process for producing a protein as claimed in any one of claims 1 to 16, which process comprises culturing a host cell containing a nucleic acid molecule which encodes the protein under conditions in which the protein is expressed, and recovering the protein.
22. A nucleic acid molecule encoding a protein as claimed in claim 1 wherein the sequence encoding one or more of the four arginine repeats of HBcAg is deleted and replaced with a restriction enzyme site unique to the nucleic acid molecule.
23. A pharmaceutical composition comprising a protein as claimed in any one of claims 1 to 16, a particle as claimed in claim 17 or a nucleic acid molecule as claimed in claim 18 or 19 and a pharmaceutically acceptable carrier or diluent.
24. A protein according to any one of claims 1 to 16, a particle according to claim 17 __ a nucleic acid molecule according to claim 18 or 19 for use in a method of prophylactic or therapeutic vaccination of the human or animal body.
25. A protein, particle or nucleic acid molecule according to claim 24 for use in a method of prophylactic or therapeutic vaccination of the human or animal body against HBV.
26. Use of a protein according to any one of claims 1 to 16, a particle according to claim 17 or a nucleic acid molecule according to claim 18 or 19 for the manufacture of a medicament for prophylactic or therapeutic vaccination of the human or animal body against HBV.
27. A method of vaccination or therapy of a subject, which method comprises administering to the subject a protein as claimed in any one of claims 1 to 16, a particle as claimed in claim 17 or a nucleic acid molecule as claimed in claimed 18 or 19.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0015308A GB0015308D0 (en) | 2000-06-22 | 2000-06-22 | Modification of hepatitis B core antigen |
| GB0015308.0 | 2000-06-22 | ||
| GB0024544.9 | 2000-10-06 | ||
| GB0024544A GB0024544D0 (en) | 2000-10-06 | 2000-10-06 | Modification of hepatitus B core antigen |
| PCT/GB2001/002817 WO2001098333A2 (en) | 2000-06-22 | 2001-06-22 | Modification of hepatitis b core antigen |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2413546A1 true CA2413546A1 (en) | 2001-12-27 |
| CA2413546C CA2413546C (en) | 2011-06-14 |
Family
ID=26244528
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2413546A Expired - Fee Related CA2413546C (en) | 2000-06-22 | 2001-06-22 | Modification of hepatitis b core antigen |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US20040054139A1 (en) |
| EP (1) | EP1294893B1 (en) |
| JP (1) | JP2004500868A (en) |
| AT (1) | ATE320493T1 (en) |
| AU (2) | AU2001266163B2 (en) |
| CA (1) | CA2413546C (en) |
| DE (1) | DE60117978T2 (en) |
| DK (1) | DK1294893T3 (en) |
| ES (1) | ES2260235T3 (en) |
| PT (1) | PT1294893E (en) |
| WO (1) | WO2001098333A2 (en) |
Families Citing this family (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU7546500A (en) * | 1999-10-08 | 2001-04-23 | Celltech Pharma Europe Limited | Designing immunogens |
| PT1268530E (en) * | 2000-04-07 | 2006-12-29 | Univ Leeds | Hepatitis b core antigen fusion proteins |
| US6942866B2 (en) | 2000-08-16 | 2005-09-13 | Apovia, Inc. | Malaria immunogen and vaccine |
| CU23002A1 (en) * | 2000-12-01 | 2004-11-18 | Ct Ingenieria Genetica Biotech | METHOD OF OBTAINING ANTIGENIC AGGREGATES AND THEIR USE IN FORMULATIONS |
| US7094409B2 (en) | 2001-01-19 | 2006-08-22 | Cytos Biotechnology Ag | Antigen arrays for treatment of allergic eosinophilic diseases |
| US7128911B2 (en) | 2001-01-19 | 2006-10-31 | Cytos Biotechnology Ag | Antigen arrays for treatment of bone disease |
| US20040146524A1 (en) * | 2002-02-21 | 2004-07-29 | Katelynne Lyons | Stabilized immunogenic HBc chimer particles |
| US20030202982A1 (en) * | 2001-08-15 | 2003-10-30 | Birkett Ashley J. | Influenza immunogen and vaccine |
| US7361352B2 (en) * | 2001-08-15 | 2008-04-22 | Acambis, Inc. | Influenza immunogen and vaccine |
| EP1450856B1 (en) | 2001-09-14 | 2009-11-11 | Cytos Biotechnology AG | Packaging of immunostimulatory cpg into virus-like particles: method of preparation and use |
| US7115266B2 (en) | 2001-10-05 | 2006-10-03 | Cytos Biotechnology Ag | Angiotensin peptide-carrier conjugates and uses thereof |
| MXPA04002644A (en) | 2001-10-05 | 2004-07-08 | Cytos Biotechnology Ag | Angiotensin peptide-carrier conjugates and uses thereof. |
| WO2003072731A2 (en) * | 2002-02-21 | 2003-09-04 | Apovia, Inc. | STABILIZED HBc CHIMER PARTICLES HAVING MENINGOCCOCAL IMMUNOGENS |
| US7351413B2 (en) * | 2002-02-21 | 2008-04-01 | Lorantis, Limited | Stabilized HBc chimer particles as immunogens for chronic hepatitis |
| CN101574518B (en) | 2002-07-18 | 2012-08-22 | 赛托斯生物技术公司 | Hapten-carrier conjugates and uses thereof |
| CN101711865A (en) | 2002-07-19 | 2010-05-26 | 希托斯生物技术股份公司 | vaccine compositions containing amyloid beta1-6 antigen arrays |
| US7537767B2 (en) | 2003-03-26 | 2009-05-26 | Cytis Biotechnology Ag | Melan-A- carrier conjugates |
| BRPI0408623A (en) | 2003-03-26 | 2006-03-07 | Cytos Biotechnology Ag | particle conjugates similar to the melan-a peptide analog virus |
| EP1651258B1 (en) * | 2003-07-30 | 2014-03-19 | Vaccine Research Institute of San Diego | Hepatitis virus core proteins as vaccine platforms and methods of use thereof |
| US7144712B2 (en) * | 2003-07-30 | 2006-12-05 | Vaccine Research Institute Of San Diego | Human hepatitis B virus core proteins as vaccine platforms and methods of use thereof |
| US7320795B2 (en) * | 2003-07-30 | 2008-01-22 | Vaccine Research Institute Of San Diego | Rodent hepatitis B virus core proteins as vaccine platforms and methods of use thereof |
| JP2008504216A (en) * | 2003-12-02 | 2008-02-14 | サイトイミューン サイエンシズ インコーポレイテッド | Methods and compositions for the production of monoclonal antibodies |
| EP1764369A1 (en) | 2005-09-16 | 2007-03-21 | Rhein Biotech Gesellschaft für neue biotechnologische Prozesse und Produkte mbH | Vaccines comprising truncated HBC core protein plus saponin-based adjuvant |
| CA2706700A1 (en) | 2007-11-08 | 2009-05-14 | Cytimmune Sciences, Inc. | Compositions and methods for generating antibodies |
| ES2622562T3 (en) | 2008-12-09 | 2017-07-06 | Pfizer Vaccines Llc | IgE CH3 peptide vaccine |
| JP2013500326A (en) | 2009-07-30 | 2013-01-07 | ファイザー バクシーンズ エルエルシー | Antigenic tau peptides and uses thereof |
| PE20161551A1 (en) | 2009-09-03 | 2017-01-18 | Pfizer Vaccines Llc | PCSK9 VACCINE |
| CA2800774A1 (en) | 2010-06-07 | 2011-12-15 | Pfizer Vaccines Llc | Ige ch3 peptide vaccine |
| WO2012131504A1 (en) | 2011-03-02 | 2012-10-04 | Pfizer Inc. | Pcsk9 vaccine |
| US9446120B2 (en) | 2011-04-15 | 2016-09-20 | Osaka University | DNA vaccine |
| KR102205077B1 (en) * | 2012-08-31 | 2021-01-20 | 고꾸리쯔 다이가꾸 호우징 오사까 다이가꾸 | Dna vaccine containing vegf-specific epitope and/or angiopoietin-2-specific epitope |
| JP6001974B2 (en) | 2012-09-21 | 2016-10-05 | アンジェスＭｇ株式会社 | DNA vaccine containing a specific epitope of apolipoprotein (a) |
| CN104341506A (en) * | 2013-07-30 | 2015-02-11 | 复旦大学 | Recombinant fusion protein and use thereof |
| EP3104877B1 (en) | 2014-02-11 | 2020-01-22 | The USA, as represented by The Secretary, Department of Health and Human Services | Pcsk9 vaccine and methods of using the same |
| WO2015133467A1 (en) * | 2014-03-06 | 2015-09-11 | 株式会社シノテスト | Vaccine against hepatitis c virus, and diagnostic hbc/hcv e2 peptide chimeric protein |
| EP3762010A4 (en) * | 2018-03-06 | 2022-04-06 | Precigen, Inc. | Hepatitis b vaccines and uses of the same |
| CN114729010A (en) * | 2019-08-29 | 2022-07-08 | 维尔生物科技有限公司 | Hepatitis B virus vaccine |
| CA3149557A1 (en) | 2019-09-30 | 2021-04-08 | Scott J. Balsitis | Hbv vaccines and methods treating hbv |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ235315A (en) * | 1989-09-19 | 1991-09-25 | Wellcome Found | Chimaeric hepadnavirus core antigen proteins and their construction |
| DE69929470T2 (en) * | 1998-11-05 | 2006-08-24 | Powderject Vaccines, Inc., Madison | GENE CONSTRUCTS FOR GENIMMUNIZATION |
-
2001
- 2001-06-22 JP JP2002504288A patent/JP2004500868A/en active Pending
- 2001-06-22 DE DE60117978T patent/DE60117978T2/en not_active Expired - Lifetime
- 2001-06-22 DK DK01943625T patent/DK1294893T3/en active
- 2001-06-22 EP EP01943625A patent/EP1294893B1/en not_active Expired - Lifetime
- 2001-06-22 AU AU2001266163A patent/AU2001266163B2/en not_active Ceased
- 2001-06-22 CA CA2413546A patent/CA2413546C/en not_active Expired - Fee Related
- 2001-06-22 WO PCT/GB2001/002817 patent/WO2001098333A2/en active IP Right Grant
- 2001-06-22 US US10/312,045 patent/US20040054139A1/en not_active Abandoned
- 2001-06-22 PT PT01943625T patent/PT1294893E/en unknown
- 2001-06-22 AT AT01943625T patent/ATE320493T1/en not_active IP Right Cessation
- 2001-06-22 AU AU6616301A patent/AU6616301A/en active Pending
- 2001-06-22 ES ES01943625T patent/ES2260235T3/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| AU2001266163B2 (en) | 2006-07-13 |
| ATE320493T1 (en) | 2006-04-15 |
| DE60117978D1 (en) | 2006-05-11 |
| US20040054139A1 (en) | 2004-03-18 |
| AU6616301A (en) | 2002-01-02 |
| PT1294893E (en) | 2006-08-31 |
| WO2001098333A2 (en) | 2001-12-27 |
| EP1294893A2 (en) | 2003-03-26 |
| CA2413546C (en) | 2011-06-14 |
| EP1294893B1 (en) | 2006-03-15 |
| WO2001098333A3 (en) | 2002-03-28 |
| ES2260235T3 (en) | 2006-11-01 |
| DK1294893T3 (en) | 2006-07-03 |
| DE60117978T2 (en) | 2006-11-02 |
| JP2004500868A (en) | 2004-01-15 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |