WO2010048615A2 - Human ebola virus species and compositions and methods thereof - Google Patents
Human ebola virus species and compositions and methods thereof Download PDFInfo
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- WO2010048615A2 WO2010048615A2 PCT/US2009/062079 US2009062079W WO2010048615A2 WO 2010048615 A2 WO2010048615 A2 WO 2010048615A2 US 2009062079 W US2009062079 W US 2009062079W WO 2010048615 A2 WO2010048615 A2 WO 2010048615A2
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- 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
- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
- C12N2760/00011—Details
- C12N2760/14011—Filoviridae
- C12N2760/14111—Ebolavirus, e.g. Zaire ebolavirus
- C12N2760/14141—Use of virus, viral particle or viral elements as a vector
- C12N2760/14143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
-
- 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
- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
- C12N2760/00011—Details
- C12N2760/14011—Filoviridae
- C12N2760/14111—Ebolavirus, e.g. Zaire ebolavirus
- C12N2760/14141—Use of virus, viral particle or viral elements as a vector
- C12N2760/14145—Special targeting system for viral vectors
-
- 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
- C12N2810/00—Vectors comprising a targeting moiety
- C12N2810/50—Vectors comprising as targeting moiety peptide derived from defined protein
- C12N2810/60—Vectors comprising as targeting moiety peptide derived from defined protein from viruses
- C12N2810/6072—Vectors comprising as targeting moiety peptide derived from defined protein from viruses negative strand RNA viruses
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/005—Assays involving biological materials from specific organisms or of a specific nature from viruses
- G01N2333/08—RNA viruses
Definitions
- the invention provides nucleic acid molecules isolated from EboIC, or fragments thereof.
- the invention provides proteins or polypeptides that are isolated from the EboIC, including viral proteins isolated from cells infected with the virus but not present in comparable uninfected cells; or fragments thereof.
- the amino acid sequences of the proteins or polypeptides are set forth in SEQ ID NOs: 11-19, or fragments thereof.
- EboBun virus of the present invention is genetically distinct, differing by more than 30% at the genome level from all other known ebolavirus species.
- BLAST Basic Local Alignment Search Tool
- NCBI National Center for Biotechnology Information
- BLAST Basic Local Alignment Search Tool
- the BLAST software suite includes various sequence analysis programs including "blastn,” that is used to align a known polynucleotide sequence with other polynucleotide sequences from a variety of databases.
- the invention provides an isolated hEbola virus including a nucleic acid molecule with a nucleotide sequence that is preferably: a) a nucleotide sequence set forth in SEQ ID NO: 1; b) a nucleotide sequence that hybridizes to the sequence set forth in SEQ ID NO: 1 under stringent conditions; or c) a nucleotide sequence that has at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity to the SEQ ID NO: 1.
- the hEbola virus is killed. In another, the virus is attenuated.
- the invention further provides antibodies that specifically bind a polypeptide of the invention encoded by the nucleotide sequence of SEQ ID NOs: 1 (EboBun) or 10 (EboIC), a fragment thereof, or encoded by a nucleic acid comprising a nucleotide sequence that hybridizes under stringent conditions to the nucleotide sequence of SEQ ID NOs: 1 (EboBun) or 10 (EboIC) and/or any hEbola EboBun epitope, having one or more biological activities of a polypeptide of the invention.
- These polypeptides include those shown in SEQ ID NOs: 2-9, 59, and 11-19.
- Such attenuated or inactivated viruses may be prepared by a series of passages of the virus through the host cells or by preparing recombinant or chimeric forms of virus. Accordingly, the present invention further provides methods of preparing recombinant or chimeric forms of the inventive hEbola viruses described herein.
- the invention provides a vaccine formulation comprising a therapeutically or prophylactic ally effective amount of the inventive hEbola virus described above, and a pharmaceutically acceptable carrier.
- the invention provides a vaccine formulation comprising a therapeutically or prophylactically effective amount of a protein extract of the inventive hEbola virus described above, or a subunit thereof; and a pharmaceutically acceptable carrier.
- the invention further provides methods of preparing recombinant or chimeric forms of hEbola.
- the invention provides vaccine preparations including the hEbola virus, including recombinant and chimeric forms of the virus, or subunits of the virus.
- the present invention encompasses recombinant or chimeric viruses encoded by viral vectors derived from the genome of the inventive hEbola virus described herein or natural variants thereof.
- a recombinant virus is one derived from the hEbola virus of Deposit Accession No. 200706291.
- the selection of the viral vector may depend on the species of the subject that is to be treated or protected from a viral infection. If the subject is human, then an attenuated hEbola virus can be used to provide the antigenic sequences.
- nucleic acids of the invention are also contemplated, provided that the essential structure and function of the peptide or polypeptide encoded by the nucleic acid are maintained.
- the nucleic acid encoding the peptide or polypeptide of this invention is optionally part of a recombinant nucleic acid construct comprising any combination of restriction sites and/or functional elements as are well known in the art which facilitate molecular cloning and other recombinant DNA manipulations.
- the present invention further provides a recombinant nucleic acid construct including a nucleic acid encoding a polypeptide of this invention.
- the isolated nucleic acids of the disclosure are optionally "overexpressed", i.e., expressed in increased levels relative to its natural expression in cells of its indigenous organism, or even relative to the expression of other proteins in the recombinant host cell.
- overexpression is assessed by a variety of methods illustratively including radio-labeling and/or protein purification. However, simple and direct methods are preferred, for example, those involving SDS/PAGE and protein staining or immunoblotting, followed by quantitative analyses, such as densitometric scanning of the resultant gel or blot.
- a gap in the sequence contig was located between fragments C and D and this was resolved using the following primers to generate a predicted fragment of 1.5 kb: forward-CTGAGAGGATCCAGAAGAAAG (SEQ ID NO: 54) and reverse-GTGTAAGCGTTGATATACCTCC (SEQ ID NO: 55).
- the terminal -20 nucleotides of the sequence were not experimentally determined but were inferred by comparing with the other known Ebola genome sequences.
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- Virology (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
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- Proteomics, Peptides & Aminoacids (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- Biophysics (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- General Engineering & Computer Science (AREA)
- General Physics & Mathematics (AREA)
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- Gastroenterology & Hepatology (AREA)
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Abstract
Description
Claims
Priority Applications (7)
Application Number | Priority Date | Filing Date | Title |
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CA2741523A CA2741523C (en) | 2008-10-24 | 2009-10-26 | Human ebola virus species and compositions and methods thereof |
US13/125,890 US20120251502A1 (en) | 2008-10-24 | 2009-10-26 | Human Ebola Virus Species and Compositions and Methods Thereof |
EP18160105.5A EP3351628B1 (en) | 2008-10-24 | 2009-10-26 | Human ebola virus species and compositions and methods thereof |
AU2009308422A AU2009308422B2 (en) | 2008-10-24 | 2009-10-26 | Human Ebola virus species and compositions and methods thereof |
EP09822840.6A EP2350270B1 (en) | 2008-10-24 | 2009-10-26 | Human ebola virus species and compositions and methods thereof |
US14/694,036 US9790473B2 (en) | 2008-10-24 | 2015-04-23 | Human Ebola virus species and compositions and methods thereof |
US15/688,421 US10428314B2 (en) | 2008-10-24 | 2017-08-28 | Human ebola virus species and compositions and methods thereof |
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US10817508P | 2008-10-24 | 2008-10-24 | |
US61/108,175 | 2008-10-24 |
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US14/694,036 Division US9790473B2 (en) | 2008-10-24 | 2015-04-23 | Human Ebola virus species and compositions and methods thereof |
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WO2010048615A2 true WO2010048615A2 (en) | 2010-04-29 |
WO2010048615A3 WO2010048615A3 (en) | 2010-11-25 |
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EP (2) | EP3351628B1 (en) |
AU (1) | AU2009308422B2 (en) |
CA (1) | CA2741523C (en) |
WO (1) | WO2010048615A2 (en) |
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WO2016134144A1 (en) * | 2015-02-20 | 2016-08-25 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Methods and reagents for detecting ebola virus |
CN107106673A (en) * | 2014-09-03 | 2017-08-29 | 巴法里安诺迪克有限公司 | Method and composition for strengthening immune response |
US9771414B2 (en) | 2015-01-26 | 2017-09-26 | Regeneron Pharmaceuticals, Inc. | Human antibodies to ebola virus glycoprotein |
CN108368557A (en) * | 2015-12-01 | 2018-08-03 | Sd生物传感器株式会社 | Including for the reporting dyes of nucleic acid isothermal amplification, quencher bi-functional oligonucleotide based on isothermal and utilize its nucleic acid amplification and assay method |
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