Modified recombinant vaccinia virus and expression vectors thereof

• US 5,762,938 A
• Filed: 08/21/1996
• Issued: 06/09/1998
• Est. Priority Date: 03/07/1991
• Status: Expired due to Term

• Current Assignee: Virogenetics Corporation
• Original Assignee: Virogenetics Corporation
• Inventors: de Taisne, Charles, Taylor, Jill, Audonnet, Jean-Christophe Francis, Tartaglia, James, Paoletti, Enzo, Cox, William I., Riviere, Michel, Pincus, Steven E., Limbach, Keith J., Gettig, Russell Robert, Johnson, Gerard P., Perkus, Marion E., Norton, Elizabeth K.
• Primary Examiner(s): Knode, Marian C.
• Assistant Examiner(s): SALIMI, ALI REZA
• Application Number:
  US08/709,209
• Time in Patent Office: 657 Days
• Field of Search: 424/199.1, 424/204.1, 424/205.1, 424/232.1, 435/320.1, 536/23.72
• US Class Current: 424/199.1
• CPC Class Codes: A61K 2039/5254 avirulent or attenuated
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 31/16 for influenza or rhinoviruses
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: A61P 31/22 for herpes viruses
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C07K 14/33 from Clostridium (G)
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C07K 2319/02 containing a signal sequence
• CPC Class Codes: C07K 2319/40 containing a tag for immunodetection, or an epitope for immunisation
• CPC Class Codes: C12N 15/86 Viral vectors
• CPC Class Codes: C12N 2710/16122 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2710/16222 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2710/16622 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2710/16722 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2710/24022 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2710/24043 : viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 2710/24122 : New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2710/24143 : viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 2730/10122 : New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2740/13022 : New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2740/15022 : New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2740/16122 : New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2740/16222 : New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2750/14322 : New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2760/12122 : New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2760/16122 : New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2760/18122 : New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2760/18422 : New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2760/18722 : New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2760/20122 : New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2770/24122 : New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2770/24322 : New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: Y10S 530/826 : Viruses

Abstract

What is described is a modified vector, such as a recombinant poxvirus, particularly recombinant vaccinia virus, having enhanced safety. The modified recombinant virus has nonessential virus-encoded genetic functions inactivated therein so that virus has attenuated virulence. In one embodiment, the genetic functions are inactivated by deleting an open reading frame encoding a virulence factor. In another embodiment, the genetic functions are inactivated by insertional inactivation of an open reading frame encoding a virulence factor. What is also described is a vaccine containing the modified recombinant virus having nonessential virus-encoded genetic functions inactivated therein so that the vaccine has an increased level of safety compared to known recombinant virus vaccines.

Claims

1. A recombinant vaccinia virus wherein regions C7L-K3L, J2R, B13R+B14R, A26L, A56R and I4L have been deleted therefrom.

5. The recombinant vaccinia virus of claim 1 including exogenous DNA from a non-vaccinia source.

10. A method for expressing a gene product in a cell cultured in vitro, which method comprises introducing into the cell the recombinant vaccinia virus as claimed in any of claims 1, 2, 3, 4, 5, 6, 7, 8 or 9, and culturing the cell under appropriate conditions for expression of the gene product.

11. An immunological composition comprising a carrier and a recombinant vaccinia virus as claimed in any of claims, 1, 2, 3, 4, 5, 6, 7, 8, 8 or 9.

2. A recombinant vaccinia virus wherein regions C23L-F4L, J2R, B13R+B14R, A26L, A56R and I4L have been deleted therefrom.

6. The recombinant vaccinia virus of claim 2 including exogenous DNA from a non-vaccinia source.

3. A recombinant vaccinia virus wherein regions C7L-K1L, J2R, B13R-B29R, A26L, A56R and I4L have been deleted therefrom.

7. The recombinant vaccinia virus of claim 3 including exogenous DNA from a non-vaccinia source.

4. A recombinant vaccinia wherein regions C23L-F4L, J2R, B13R-B29R, A26L, A56 and I4L have been deleted therefrom.

8. The recombinant vaccinia virus of claim 4 including exogenous DNA from a non-vaccinia source.

9. A recombinant vaccinia virus selected from the group consisting of:

vP954, vP938, vP953, vP977, vP996, vP1006 and vP1015.