Modified vaccinia ankara virus variant

• US 20030202988A1
• Filed: 05/16/2003
• Published: 10/30/2003
• Est. Priority Date: 11/23/2000
• Status: Active Grant

• Current Assignee: Bavarian Nordic A/S
• Original Assignee: Bavarian Nordic A/S
• Inventors: Chaplin, Paul, Howley, Paul, Meisinger, Christine
• Granted Patent: US 6,761,893 B2
• Time in Patent Office: Days
• US Class Current: 424/232.1
• CPC Class Codes: A61K 2039/5254 avirulent or attenuated
• CPC Class Codes: A61K 2039/5256 expressing foreign proteins
• CPC Class Codes: A61K 2039/53 DNA (RNA) vaccination
• CPC Class Codes: A61K 2039/545 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/285 Vaccinia virus or variola virus
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• 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 33/02 Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C12N 15/86 Viral vectors
• CPC Class Codes: C12N 2710/24121 : Viruses as such, e.g. new isolates, mutants or their genomic sequences
• CPC Class Codes: C12N 2710/24143 : viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 2740/16322 : New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 7/00 : Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00

Abstract

The present invention provides an attenuated virus, which is derived from Modified Vaccinia Ankara virus and characterized by the loss of its capability to reproductively replicate in human cell lines. It further describes recombinant viruses derived from this virus and the use of the virus, or its recombinants, as a medicament or vaccine. A method is provided for inducing an immune response in individuals who may be immune-compromised, receiving antiviral therapy, or have a pre-existing immunity to the vaccine virus. In addition, a method is provided for the administration of a therapeutically effective amount of the virus, or its recombinants, in a vaccinia virus prime/vaccinia virus boost innoculation regimen.

Claims

1. ) A method for inducing a specific immune response in a living animal body, including a human, comprising administering an amount of a vaccinia preparation which includes an effective amount of a vaccinia virus having at least one of the following advantageous properties:

(i) capability of reproductive replication in vitro in chicken embryo fibroblasts (CEF), but no capability of reproductive replication in a human cell line known to permit replication with known vaccinia strains,

(ii) failure to replicate in vivo in those animals including humans in which the virus is used as a vaccine or active ingredient of a pharmaceutical composition,

(iii) induction of a higher specific immune response compared to a known vaccinia strain, and/or

(iv) induction of at least the same level of a specific immune response in vaccinia virus prime/vaccinia virus boost regimes when compared to DNA-prime/vaccinia virus boost regimes,

wherein the preparation is administered in therapeutically effective amounts in a first inoculation or “

priming inoculation” and

in a second inoculation or “

boosting inoculation”

.

2. ) The method of claim 1, wherein the vaccinia virus has at least two (2) of the advantageous properties.

3. ) The method of claim 1, wherein the vaccinia virus has at least three (3) of the advantageous properties.

4. ) The method of claim 1, wherein the vaccinia virus has all four (4) of the advantageous properties.

5. ) The method of claim 1, wherein the vaccinia virus is not capable of reproductive replication in the human keratinocyte cell line (HaCat).

6. ) The method of claim 1, wherein the vaccinia virus is not capable of reproductive replication in any of the following human cell lines:

the human keratinocyte cell line (HaCat), the human embryo kidney cell line (293), the human bone osteosarcoma cell line (143B), and the human cervix adenocarcinoma cell line (HeLa).

7. ) The method of claim 1, wherein the vaccinia virus is capable of a replication amplification ratio of greater than 500 in CEF cells.

8. ) The method of claim 1, wherein the vaccinia virus is not capable of replication in mammals.

9. ) The method of claim 1, wherein the vaccinia virus is not capable of replication in humans.

10. ) The method of claim 1, wherein the known vaccinia strain is a Modified Vaccinia Ankara virus (MVA).

11. ) The method of claim 1, wherein the known vaccinia strain is MVA 572.

12. ) The method of claim 1, wherein the known vaccinia strain is MVA 575.

13. ) The method of claim 1, in which the vaccinia virus is that virus deposited at the European Collection of Cell Cultures (ECACC), Salisbury (UK) under number V00083008 and derivatives thereof.

14. ) The method of claim 1, wherein the vaccinia virus is monoclonal.

15. ) The method of claim 1, wherein the vaccinia virus is not capable of replicating in immune compromised animals, including humans.

16. ) The method of claim 1, wherein the vaccinia virus comprises at least one heterologous nucleic acid sequence.

17. ) The method of claim 1, wherein the vaccinia virus comprises a heterologous nucleic acid sequence selected from a sequence coding for at least one antigen, antigenic epitope, or a therapeutic compound.

18. ) The method of claim 1, wherein the specific immune response is directed to the vaccinia virus

19. ) The method of claim 1, wherein the specific immune response is directed to heterologous material encoded in the vaccinia virus.

20. ) The method of claim 1, wherein the specific immune response is directed to HIV.

21. ) The method of claim 1, wherein the specific immune response is two (2) fold.

22. ) The method of claim 1, wherein the specific immune response is a specific immunity to an orthopox.

23. ) The method of claim 22, wherein the specific immune response is a specific immunity to smallpox.

24. ) The method of claim 1, comprising the administration of at least 10² tissue culture infectious dose (TCID₅₀) of the vaccinia virus.

25. ) The method of claim 1, comprising the administration of a genome or functional parts of the vaccinia virus, to induce a specific immune response.

26. ) The method of claim 1, wherein the vaccinia virus, genome, or functional part thereof, is administered as adjuvant.