MVA vaccine

• US 20080075694A1
• Filed: 07/19/2007
• Published: 03/27/2008
• Est. Priority Date: 01/24/2005
• Status: Abandoned Application

• Current Assignee: Helmholtz Zentrum München Deutsches Forschungszentrum für. Gesundheit und Umwelt (GmbH)
• Original Assignee: Helmholtz Zentrum München Deutsches Forschungszentrum für. Gesundheit und Umwelt (GmbH)
• Inventors: Gasteiger, Georg, Drexler, Ingo, Erfle, Volker, Sutter, Gerd
• Application Number:
  US11/880,018
• Publication Number:
  US 20080075694A1
• Time in Patent Office: Days
• US Class Current: 424/85.4
• CPC Class Codes: A61K 2039/5256 expressing foreign proteins
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 33/00 Antiparasitic agents
• 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: C12N 15/86 Viral vectors
• CPC Class Codes: C12N 2710/24143 viral genome or elements thereof as genetic vector
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention is directed to a recombinant MVA, which carries a nucleic acid sequence coding for a fusion protein. The present invention is further directed to a kit of parts containing said recombinant MVA as well as to a method for enhancing T cell responses in a mammal.

Claims

1. A kit of parts comprising the following components:

a) a first component comprising one or more foreign proteins or a nucleic acid encoding same or functional parts thereof, which functional parts contain one or more substitutions, insertions and/or deletions when compared to the wild type protein whilst having the same function as the wild type protein; and

b) a second component comprising a recombinant Modified Vaccinia Virus Ankara (MVA), which carries a nucleic acid sequence coding for a fusion protein comprising;

Ubiquitin or a functional part thereof, which functional part contains one or more substitutions, insertions and/or deletions when compared to the wild type protein whilst having the same function as the wild type protein; and

one or more foreign proteins, i.e. one or more proteins not naturally present as a part of MVA or functional parts thereof, which functional part contains one or more substitutions, insertions and/or deletions when compared to the wild type protein whilst having the same function as the wild type protein;

wherein the first and second components optionally further comprise a pharmaceutically acceptable carrier.

2. The kit of claim 1, wherein the fusion protein further comprises a linker between Ubiquitin and the foreign protein.

3. The kit of claim 1, wherein the foreign protein is a heterologous protein derived from the group consisting of therapeutic polypeptides and polypeptides of pathogenic agents and functional parts thereof.

4. The kit of claim 3, wherein the therapeutic polypeptide is derived from the group consisting of secreted proteins, e.g. polypeptides of antibodies, chemokines, cytokines or interferons.

5. The kit of claim 3, wherein the pathogenic agent is derived from the group consisting of viruses, bacteria, protozoa and parasites as well as tumor cells or tumor cell associated antigens and functional parts thereof.

6. The kit of claim 5, wherein the viruses are selected from the group consisting of influenza viruses, measles and respiratory syncytial viruses, dengue viruses, human immunodeficiency viruses, human hepatitis viruses, herpes viruses, or papilloma viruses.

7. The kit of claim 5, wherein the protozoa is Plasmodium falciparum.

8. The kit of claim 5, wherein the bacteria is tuberculosis-causing Mycobacteria.

9. The kit of claim 5, wherein the tumor cell associated antigen is selected from the group consisting of melanoma-associated differentiation antigens, e.g. tyrosinase, tyrosinase-related proteins 1 and 2, of cancer testes antigens, e.g. MAGE-1,-2,-3, and BAGE, and of non-mutated shared antigens overexpressed on tumors, e.g. Her-2/neu, MUC-1, and p53.

10. The kit of claim 1, wherein the fusion protein and/or foreign protein coding regions are each flanked by DNA-sequences, flanking a non-essential site within the MVA genome.

11. The kit of claim 10, wherein the non-essential site is the site of deletion III in the MVA genome.

12. The kit of claim 1, wherein the ratio of the amount of the first component to the second component is from 1:

5 to 1;

20, preferably 1;

10, measured as infectious units (IU) of recombinant MVA particles.

13. The kit of claim 1 for use in the anti-cancer therapy or in the prevention of infectious diseases.

14. A method for enhancing T cell responses in a mammal, the method comprising the steps of:

a) providing the kit of claim 1;

b) priming a mammal with an amount of the first component effective to provide a primary immune response;

c) boosting said mammal with an amount of the second component effective to provide a secondary immune response.

15. The method of claim 14, wherein the method is provided for treating cancer or for the prevention of infectious diseases.

16. The method of claim 14, wherein the boosting step is performed at week 2-12, preferably 4-8 after the priming step.

17. The method of claim 14, which is a vaccination method.

18. The method of claim 14, wherein the animal treated is a human being.

19. Use of a recombinant MVA, which carries a nucleic acid sequence coding for a fusion protein comprising:

Ubiquitin or a functional part thereof, which functional parts contain one or more substitutions, insertions and/or deletions when compared to the wild type protein whilst having the same function as the wild type protein; and

one or more foreign proteins, i.e. one or more proteins not naturally present as a part of MVA or a functional part thereof, which functional part contains one or more substitutions, insertions and/or deletions when compared to the wild type protein whilst having the same function as the wild type protein,

in anti-cancer therapy or in the prevention of infectious diseases as a boosting agent in prime-boost vaccinations.