CA2303477A1 - Chimaeric adenoviruses - Google Patents

Chimaeric adenoviruses Download PDF

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Publication number
CA2303477A1
CA2303477A1 CA002303477A CA2303477A CA2303477A1 CA 2303477 A1 CA2303477 A1 CA 2303477A1 CA 002303477 A CA002303477 A CA 002303477A CA 2303477 A CA2303477 A CA 2303477A CA 2303477 A1 CA2303477 A1 CA 2303477A1
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CA
Canada
Prior art keywords
adenovirus
chimaeric
serotype
adenoviruses
vector
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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.)
Granted
Application number
CA002303477A
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French (fr)
Other versions
CA2303477C (en
Inventor
Menzo Havenga
Ronald Vogels
Abraham Bout
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Janssen Vaccines and Prevention BV
Original Assignee
Introgene B.V.
Menzo Havenga
Ronald Vogels
Abraham Bout
Crucell Holland B.V.
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Filing date
Publication date
Application filed by Introgene B.V., Menzo Havenga, Ronald Vogels, Abraham Bout, Crucell Holland B.V. filed Critical Introgene B.V.
Publication of CA2303477A1 publication Critical patent/CA2303477A1/en
Application granted granted Critical
Publication of CA2303477C publication Critical patent/CA2303477C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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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
    • 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
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/86—Viral vectors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • 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
    • 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
    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/10011—Adenoviridae
    • C12N2710/10311—Mastadenovirus, e.g. human or simian adenoviruses
    • C12N2710/10322—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
    • 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
    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/10011—Adenoviridae
    • C12N2710/10311—Mastadenovirus, e.g. human or simian adenoviruses
    • C12N2710/10341—Use of virus, viral particle or viral elements as a vector
    • C12N2710/10344—Chimeric viral vector comprising heterologous viral elements for production of another viral 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
    • C12N2760/20011—Rhabdoviridae
    • C12N2760/20111—Lyssavirus, e.g. rabies virus
    • C12N2760/20134—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

Abstract

The present invention provides methods and vector systems for the generation of chimaeric recombinant adenoviruses. These hybrid adenoviruses contain a genome that is derived from different adenovirus serotypes. In particular, novel hybrid adenoviruses are disclosed with improved properties for gene therapy purposes. These properties include:
a decreased sensitivity towards neutralizing antibodies, a modified host range, a change in the titer to which adenovirus can be grown, the ability to escape trapping in the liver upon in vivo systemic delivery, and absence or decreased infection of antigen presenting cells (APC) of the immune system, such as macrophages or dendritic cells. These chimaeric adenoviruses thus represent improved tools for gene therapy and vaccination since they overcome the limitations observed with the currently used serotype subgroup C adenoviruses.

Claims (10)

1. A chimaeric adenovirus comprising at least a part of a fiber protein of an adenovirus serotype providing the chimaeric virus with a desired host range and at least a part of a penton or hexon protein from another less antigenic adenovirus serotype resulting in a less antigenic chimaeric adenovirus.
2. A recombinant vector derived from an adenovirus comprising at least one ITR and a packaging signal having an insertion site for a nucleic acid sequence of interest, and further having an insertion site for functionallly inserting a gene encoding a penton and/or a hexon protein of a first serotype of adenovirus and having an insertion site for a gene encoding a fiber protein of a second adenovirus of a different serotype.
3. A recombinant vector according to claim 2 which is a plasmid.
4. A packaging cell for producing a chimaeric adenovirus according to claim 1, comprising in trans all elements necessary for adenovirus production not present on the adenoviral vector according to claim 2.
5. A kit of parts comprising a packaging cell according to claim 4 and a recombinant vector according to claim 2 or 3, whereby there is essentially no overlap leading to recombination resulting in the production of replication competent adenovirus between said cell and said vector.
6. A vector according to claim 2 or 3 where the insertion sites are different and preferably unique restriction sites.
7. A method for producing a chimaeric adenovirus having a desired host range and diminished antigenicity, comprising providing a vector according to claim 2, inserting into said vector at least a functional part of a penton or hexon protein derived from an adenovirus serotype having relatively low antigenicity, inserting at least a functional part of a fiber protein derived from an adenovirus serotype having the desired host range and transfecting said vector in a packaging cell according to claim 4 and allowing for production of chimaeric viral particles.
8. A method according to claim 7, wherein said reduced antigenicity is a diminished capability to raise neutralizing antibodies.
9. A chimaeric adenovirus according to claim 1, wherein the hexon, penton and/or fiber proteins are chimaeric proteins originating from different adenovirus serotypes.
10. A nucleic acid library comprising nucleic acid derived from different adenovirus serotypes.
CA2303477A 1998-07-08 1999-07-08 Chimaeric adenoviruses Expired - Fee Related CA2303477C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP98202297 1998-07-08
EP98202297.2 1998-07-08
PCT/NL1999/000436 WO2000003029A2 (en) 1998-07-08 1999-07-08 Chimaeric adenoviruses

Publications (2)

Publication Number Publication Date
CA2303477A1 true CA2303477A1 (en) 2000-01-20
CA2303477C CA2303477C (en) 2010-04-06

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
CA2303477A Expired - Fee Related CA2303477C (en) 1998-07-08 1999-07-08 Chimaeric adenoviruses

Country Status (10)

Country Link
US (3) US20030017138A1 (en)
EP (1) EP0978566B1 (en)
JP (1) JP4472178B2 (en)
AT (1) ATE325200T1 (en)
AU (1) AU765276B2 (en)
CA (1) CA2303477C (en)
DE (1) DE69931112T2 (en)
ES (1) ES2263250T3 (en)
NZ (1) NZ503018A (en)
WO (1) WO2000003029A2 (en)

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