WO1994006913B1 - Recombinant proteins of a pakistani strain of hepatitis e and their use in diagnostic methods and vaccines - Google Patents
Recombinant proteins of a pakistani strain of hepatitis e and their use in diagnostic methods and vaccinesInfo
- Publication number
- WO1994006913B1 WO1994006913B1 PCT/US1993/008849 US9308849W WO9406913B1 WO 1994006913 B1 WO1994006913 B1 WO 1994006913B1 US 9308849 W US9308849 W US 9308849W WO 9406913 B1 WO9406913 B1 WO 9406913B1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- protein
- recombinant
- reading frame
- hepatitis
- expression vector
- Prior art date
Links
- 229960005486 vaccines Drugs 0.000 title claims abstract 4
- 102000007312 Recombinant Proteins Human genes 0.000 title claims 9
- 108010033725 Recombinant Proteins Proteins 0.000 title claims 9
- 208000006454 Hepatitis Diseases 0.000 title abstract 2
- 231100000283 hepatitis Toxicity 0.000 title abstract 2
- 238000002405 diagnostic procedure Methods 0.000 title 1
- 102000004169 proteins and genes Human genes 0.000 claims abstract 21
- 108090000623 proteins and genes Proteins 0.000 claims abstract 21
- 241000156302 Porcine hemagglutinating encephalomyelitis virus Species 0.000 claims abstract 8
- 241000724675 Hepatitis E virus Species 0.000 claims abstract 5
- 201000010284 hepatitis E Diseases 0.000 claims abstract 5
- 201000009910 diseases by infectious agent Diseases 0.000 claims abstract 2
- 229920002676 Complementary DNA Polymers 0.000 claims 13
- 239000002299 complementary DNA Substances 0.000 claims 13
- 108090001123 antibodies Proteins 0.000 claims 5
- 102000004965 antibodies Human genes 0.000 claims 5
- 125000003275 alpha amino acid group Chemical group 0.000 claims 4
- 238000003259 recombinant expression Methods 0.000 claims 4
- 229920001850 Nucleic acid sequence Polymers 0.000 claims 3
- 108010047814 Antigen-Antibody Complex Proteins 0.000 claims 2
- 241000124008 Mammalia Species 0.000 claims 2
- 239000012472 biological sample Substances 0.000 claims 2
- 230000015572 biosynthetic process Effects 0.000 claims 2
- 239000000969 carrier Substances 0.000 claims 2
- 210000003527 eukaryotic cell Anatomy 0.000 claims 2
- 238000003306 harvesting Methods 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 238000003786 synthesis reaction Methods 0.000 claims 2
- 230000002194 synthesizing Effects 0.000 claims 2
- 210000004369 Blood Anatomy 0.000 claims 1
- 210000001175 Cerebrospinal Fluid Anatomy 0.000 claims 1
- 241000238631 Hexapoda Species 0.000 claims 1
- 210000002381 Plasma Anatomy 0.000 claims 1
- 210000004910 Pleural fluid Anatomy 0.000 claims 1
- 108020004511 Recombinant DNA Proteins 0.000 claims 1
- 210000002966 Serum Anatomy 0.000 claims 1
- 210000002700 Urine Anatomy 0.000 claims 1
- 230000003321 amplification Effects 0.000 claims 1
- 239000008280 blood Substances 0.000 claims 1
- 210000004027 cells Anatomy 0.000 claims 1
- 238000010367 cloning Methods 0.000 claims 1
- 229920003013 deoxyribonucleic acid Polymers 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 230000003053 immunization Effects 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 238000003199 nucleic acid amplification method Methods 0.000 claims 1
- 230000001681 protective Effects 0.000 claims 1
- 239000000523 sample Substances 0.000 claims 1
- 239000007787 solid Substances 0.000 claims 1
- 210000001519 tissues Anatomy 0.000 claims 1
- 241000701447 unidentified baculovirus Species 0.000 claims 1
- 239000000427 antigen Substances 0.000 abstract 1
- 102000038129 antigens Human genes 0.000 abstract 1
- 108091007172 antigens Proteins 0.000 abstract 1
- 230000002163 immunogen Effects 0.000 abstract 1
- 239000002245 particle Substances 0.000 abstract 1
Abstract
A strain of hepatitis E virus from Pakistan (SAR-55) implicated in an epidemic of enterically transmitted non-A, non-B hepatitis, now called hepatitis E, is disclosed. The invention relates to the expression of the whole structural region of SAR-55, designated open reading frame 2 (ORF-2), in a eukaryotic expression system. The expressed protein is capable of forming HEV virus-like particles which can serve as an antigen in diagnostic immunoassays and as an immunogen or vaccine to protect against infection by hepatitis E.
Claims
1. A cDNA of isolated and purified hepatitis E virus strain SAR-55.
2. The cDNA of claim 1, wherein the cDNA has a cDNA sequence according to SEQ ID No. 4.
3. A synthetic DNA sequence comprising a sequence capable of directing host organism synthesis of at least one complete open reading frame protein, said protein having substantial homology to a protein from HEV strain SAR-55, or a variant of said protein.
4. A DNA sequence of Claim 3, wherein said DNA encodes a protein comprising the amino acid sequence of SEQ ID NO. 2 or a variant thereof.
5. A recombinant protein derived from the cDNA sequence of claim 2.
6. The recombinant protein of claim 5 wherein the protein is encoded by cDNA sequence comprising a complete ORF.
7. The recombinant protein of claim 6, wherein said protein comprises an amino acid sequence of SEQ ID NO. 2 or substantially homologous sequence thereof.
8. A recombinant protein derived from a complete open-reading frame of a hepatitis E virus.
9. The recombinant protein of claim 8, wherein said protein is derived from complete open reading frame 2 of a hepatitis E virus.
10. A method of producing a recombinant HEV protein, - 96 -
comprising:
(a) cloning a cDNA sequence of HEV strain SAR-55;
(b) inserting the cDNA sequence into an expression vector;
(c) transferring the expression vector into a host organism;
(d) culturing the host organism under conditions appropriate for amplification of the vector and expression of the protein; and
(e) harvesting the protein.
11. The method of claim 10, wherein the expression vector is a eukaryotic expression vector.
12. The method of claim 10, wherein the expression vector is a baculovirus vector.
13. The method of claim 10, wherein the host organism is a eukaryotic cell.
14. The method of claim 13, wherein the eukaryotic cell is an insect cell.
15. The method of claim 10, wherein the cDNA sequence encodes a complete open-reading frame.
16. The method of claim 15, wherein the cDNA sequence encodes complete open-reading frame 2.
17. The method of claim 16, wherein the protein comprises an amino acid sequence according to SEQ ID NO:2 or a variant thereof.
18. A recombinant expression vector comprising a cDNA sequence according to claim 2. - 97 -
19. The recombinant vector of claim 17, wherein said vector comprises a cDNA sequence encoding a complete open- reading frame.
20. The recombinant expression vector of claim 18, wherein the cDNA sequence encodes a complete open-reading frame 2.
21. The recombinant expression vector of claim 19, wherein the vector is p63-2.
22. A host organism transformed or transfected with a recombinant expression vector according to claim 18, 19, 20 or 21.
23. A method for the recombinant DNA synthesis of at least one complete open reading frame protein of HEV comprising:
(a) culturing a transformed or transfected host organism containing a DNA sequence capable of directing the host organism to produce an open reading frame protein of a hepatitis E virus under conditions such that the protein is produced;
(b) harvesting the protein.
24. The method of claim 23, wherein the protein produced in step (a) comprises open reading frame 2.
25. A method of detecting antibodies to Hepatitis E in a biological sample suspected of containing said anti¬ bodies comprising:
(a) contacting the sample with the recombinant HEV protein of claims 5 or 8 to form an immune complex with the antibodies; and (b) detecting the presence of the immune - 98 -
complex.
26. The method of claim 25, wherein the biological sample is whole blood, plasma, serum, cerebrospinal fluid, tissue, urine and pleural fluid.
27. The method of claim 25, wherein Ig or IgG anti¬ body is detected.
28. The method of claim 25, wherein the recombinant HEV protein is bound to a solid support.
29-. The method of claim 25, wherein the immune complex is detected using a labeled antibody.
30. A kit for use in a method of claim 25 comprising: a recombinant HEV protein comprising an amino acid sequence of SEQ ID No. 2 or a substantially homologous sequence thereof.
31. The kit of claim 30 further comprising a labeled secondary antibody.
32. A pharmaceutical composition comprising the recombinant protein of claims 5 or 8 and a suitable excipient, diluent or carrier.
33. A method of preventing hepatitis E, comprising administering the pharmaceutical composition of claim 32 to a mammal in an effective amount to stimulate the production of protective antibody.
34. A vaccine for immunizing a mammal against hepatitis E infection, comprising a recombinant protein according to claims 5 or 8 in a pharmacologically acceptable carrier. - 99 -
35. The vaccine of claim 34, wherein the recombinant protein is derived from a complete open reading frame 2.
Priority Applications (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP93922703A EP0662133B1 (en) | 1992-09-18 | 1993-09-17 | Recombinant proteins of a pakistani strain of hepatitis e and their use in diagnostic methods and vaccines |
| JP6508363A JPH08504096A (en) | 1992-09-18 | 1993-09-17 | Recombinant proteins of hepatitis E Pakistan strains and their use in diagnostics and vaccines |
| DE69334299T DE69334299D1 (en) | 1992-09-18 | 1993-09-17 | RECOMBINANT PROTEINS OF A PAKISTANI TRIBRAY OF HEPATITIS E-VIRUS AND THEIR USE IN DIAGNOSTIC PROCEDURES AND AS VACCINE |
| AU51625/93A AU689447C (en) | 1992-09-18 | 1993-09-17 | Recombinant proteins of a pakistani strain of hepatitis E and their use in diagnostic methods and vaccines |
| AT93922703T ATE449178T1 (en) | 1992-09-18 | 1993-09-17 | RECOMBINANT PROTEINS OF A PAKISTANI STRAIN OF HEPATITIS E VIRUS AND THEIR USE IN DIAGNOSTIC PROCEDURES AND AS A VACCINE |
| CA002144855A CA2144855C (en) | 1992-09-18 | 1993-09-17 | Recombinant proteins of a pakistani strain of hepatitis e and their use in diagnostic methods and vaccines |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US94726392A | 1992-09-18 | 1992-09-18 | |
| US07/947,263 | 1992-09-18 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| WO1994006913A2 WO1994006913A2 (en) | 1994-03-31 |
| WO1994006913A3 WO1994006913A3 (en) | 1994-06-09 |
| WO1994006913B1 true WO1994006913B1 (en) | 1994-08-04 |
Family
ID=25485852
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1993/008849 WO1994006913A2 (en) | 1992-09-18 | 1993-09-17 | Recombinant proteins of a pakistani strain of hepatitis e and their use in diagnostic methods and vaccines |
Country Status (9)
| Country | Link |
|---|---|
| US (3) | US6706873B1 (en) |
| EP (1) | EP0662133B1 (en) |
| JP (3) | JPH08504096A (en) |
| KR (2) | KR100318516B1 (en) |
| AT (1) | ATE449178T1 (en) |
| CA (1) | CA2144855C (en) |
| DE (1) | DE69334299D1 (en) |
| ES (1) | ES2336282T3 (en) |
| WO (1) | WO1994006913A2 (en) |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5686239A (en) * | 1988-06-17 | 1997-11-11 | Genelabs Technologies, Inc. | Hepatitis E virus peptides and methods |
| US6291641B1 (en) | 1988-06-17 | 2001-09-18 | Genelabs Technologies, Inc. | Hepatitis E virus antigens and uses therefor |
| US6214970B1 (en) | 1988-06-17 | 2001-04-10 | Genelabs Technologies, Inc. | Hepatitis E virus antigens and uses therefor |
| US6455492B1 (en) * | 1988-06-17 | 2002-09-24 | Genelabs Technologies, Inc. | Hepatitis E virus vaccine and method |
| ES2336282T3 (en) | 1992-09-18 | 2010-04-09 | The Government Of The Usa, As Represented By The Secretary, Department Of Health And Human Services | RECOMBINANT PROTEINS OF A PAQUISTANI CEPA OF HEPATITIS E AND ITS USE IN METHODS OF DIAGNOSIS AND VACCINES. |
| US6787145B1 (en) | 1992-09-18 | 2004-09-07 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Recombinant proteins of a pakistani strain of hepatitis E and their use in diagnostic methods and vaccines |
| US6207416B1 (en) | 1992-09-18 | 2001-03-27 | The United States Of America As Represented By The Department Of Health And Human Services | Recombinant proteins of a Pakistani strain of hepatitis E and their use in diagnostic methods and vaccines |
| AU694139B2 (en) * | 1993-09-24 | 1998-07-16 | Macfarlane Burnet Centre For Medical Research Limited, The | Immunoreactive antigens of hepatitis E virus |
| AU712901B2 (en) * | 1994-10-03 | 1999-11-18 | Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services, The | Recombinant proteins of a pakistani strain of hepatitis E and their use in diagnostic methods and vaccines |
| US6054567A (en) * | 1997-04-11 | 2000-04-25 | The United States Of America As Represented By The Department Of Health And Human Services | Recombinant proteins of a pakistani strain of hepatitis E and their use in diagnostic methods and vaccines |
| US6458562B1 (en) | 1998-04-09 | 2002-10-01 | The United States Of America As Represented By The Secretary Of Health And Human Services | Recombinant proteins of a Pakistani strain of hepatitis E and their use in diagnostic methods and vaccines |
| ATE364631T1 (en) * | 1999-12-01 | 2007-07-15 | Us Gov Health & Human Serv | MAIN NEUTRALIZATION SITE OF THE HEPATITIS E VIRUS AND USE OF THIS NEUTRALIZATION SITE IN VACCINATION PROCEDURES AND IN PROCESSES FOR SCREENING FOR NEUTRALIZATION ANTIBODIES |
| WO2002089733A2 (en) * | 2001-05-07 | 2002-11-14 | The Government Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Recombinant orf2 proteins of the swine hepatitis e virus and their use as a vaccine and as a diagnostic reagent for medical and veterinary applications |
| WO2003040187A1 (en) * | 2001-11-08 | 2003-05-15 | Yang Sheng Tang Company Limited | Hepatitis e virus monoclonal antibodies or the binding fragments of it and the use thereof |
| WO2003064679A2 (en) * | 2002-01-30 | 2003-08-07 | Id Biomedical Corporation | Methods for detecting vancomycin-resistant microorganisms and compositions therefor |
| WO2006016238A2 (en) * | 2004-08-04 | 2006-02-16 | Applied Research Systems Ars Holding N.V. | Capsules containing transfected cells, method for preparing the same and uses thereof for immunization and vaccination |
| US9487837B2 (en) | 2008-10-06 | 2016-11-08 | Morehouse School Of Medicine | Exosome-mediated diagnosis of hepatitis virus infections and diseases |
| US8906863B2 (en) | 2009-02-27 | 2014-12-09 | The Regents Of The University Of California | Proteolysis-resistant capsid of chimeric hepatitis E virus as an oral delivery vector |
| US8906862B2 (en) | 2009-02-27 | 2014-12-09 | The Regents Of The University Of California | Multiple antigen delivery system using hepatitis E virus-like particle |
| JP5869885B2 (en) * | 2009-02-27 | 2016-02-24 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | Multi-antigen delivery system using hepatitis E virus-like particles |
| KR101648106B1 (en) * | 2014-04-29 | 2016-08-17 | 대한민국 | Dual expression of the structural proteins of hepatitis A virus and hepatitis E viurs and its applications as a vaccine or a diagnostic tool |
| KR102492326B1 (en) | 2022-07-14 | 2023-01-26 | 김성남 | Portable odor emission self-defense device |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5024939A (en) * | 1987-07-09 | 1991-06-18 | Genentech, Inc. | Transient expression system for producing recombinant protein |
| US6455492B1 (en) | 1988-06-17 | 2002-09-24 | Genelabs Technologies, Inc. | Hepatitis E virus vaccine and method |
| US5741490A (en) | 1988-06-17 | 1998-04-21 | Genelabs Technologies, Inc. | Hepatitis E virus vaccine and method |
| US6214970B1 (en) | 1988-06-17 | 2001-04-10 | Genelabs Technologies, Inc. | Hepatitis E virus antigens and uses therefor |
| US5686239A (en) * | 1988-06-17 | 1997-11-11 | Genelabs Technologies, Inc. | Hepatitis E virus peptides and methods |
| US5885768A (en) | 1988-06-17 | 1999-03-23 | The United States Of America As Represented By The Department Of Health And Human Services | Hepatitis E virus peptide antigen and antibodies |
| DE69133599D1 (en) | 1990-04-05 | 2008-08-21 | Genelabs Tech Inc | ENTERICALLY TRANSMITTING NON-A / NON-B HEPATITIS VIRUS AGENS AND CHARACTERISTIC EPITOPES OF SELF |
| WO1993014203A1 (en) | 1992-01-21 | 1993-07-22 | Tsumura & Co. | Lymphotoxins, expression vector therefor, and production of lymphotoxins with said vector |
| ES2336282T3 (en) | 1992-09-18 | 2010-04-09 | The Government Of The Usa, As Represented By The Secretary, Department Of Health And Human Services | RECOMBINANT PROTEINS OF A PAQUISTANI CEPA OF HEPATITIS E AND ITS USE IN METHODS OF DIAGNOSIS AND VACCINES. |
| US6207416B1 (en) * | 1992-09-18 | 2001-03-27 | The United States Of America As Represented By The Department Of Health And Human Services | Recombinant proteins of a Pakistani strain of hepatitis E and their use in diagnostic methods and vaccines |
| AU694139B2 (en) | 1993-09-24 | 1998-07-16 | Macfarlane Burnet Centre For Medical Research Limited, The | Immunoreactive antigens of hepatitis E virus |
| CA2179609A1 (en) | 1993-12-22 | 1995-06-29 | Deborah A. Paul | Monoclonal antibodies against hev orf-2 and methods for using same |
| US9115603B2 (en) * | 2012-07-24 | 2015-08-25 | Electratherm, Inc. | Multiple organic Rankine cycle system and method |
-
1993
- 1993-09-17 ES ES93922703T patent/ES2336282T3/en not_active Expired - Lifetime
- 1993-09-17 JP JP6508363A patent/JPH08504096A/en not_active Withdrawn
- 1993-09-17 WO PCT/US1993/008849 patent/WO1994006913A2/en active Application Filing
- 1993-09-17 EP EP93922703A patent/EP0662133B1/en not_active Expired - Lifetime
- 1993-09-17 CA CA002144855A patent/CA2144855C/en not_active Expired - Fee Related
- 1993-09-17 DE DE69334299T patent/DE69334299D1/en not_active Expired - Lifetime
- 1993-09-17 AT AT93922703T patent/ATE449178T1/en not_active IP Right Cessation
-
1994
- 1994-10-03 US US08/316,765 patent/US6706873B1/en not_active Expired - Fee Related
-
1995
- 1995-06-06 US US08/471,971 patent/US6287759B1/en not_active Expired - Lifetime
- 1995-06-06 US US08/470,246 patent/US6696242B1/en not_active Expired - Fee Related
- 1995-10-03 KR KR1020007010531A patent/KR100318516B1/en not_active IP Right Cessation
- 1995-10-03 KR KR1020007003415A patent/KR100332602B1/en not_active IP Right Cessation
-
2004
- 2004-04-07 JP JP2004113548A patent/JP2005013220A/en not_active Withdrawn
-
2005
- 2005-12-28 JP JP2005377429A patent/JP2006149393A/en active Pending
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