Vaccines using nucleic acid-lipid complexes

• US 20030022854A1
• Filed: 11/30/2001
• Published: 01/30/2003
• Est. Priority Date: 06/25/1998
• Status: Abandoned Application

• Current Assignee: National Jewish Medical and Research Center
• Original Assignee: National Jewish Medical and Research Center
• Inventors: Johannes Schwarze, Jurgen Karl, Gelfand, Erwin W., Dow, Steven W., Elmslie, Robyn E.
• Application Number:
  US10/012,597
• Publication Number:
  US 20030022854A1
• Time in Patent Office: Days
• US Class Current: 514/44
• CPC Class Codes: A61K 2039/5152 Tumor cells
• CPC Class Codes: A61K 2039/53 DNA (RNA) vaccination
• CPC Class Codes: A61K 2039/55555 Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
• CPC Class Codes: A61K 2039/57 characterised by the type of response, e.g. Th1, Th2
• CPC Class Codes: A61K 2239/31 characterized by the route of administration
• CPC Class Codes: A61K 2239/38 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 38/20 Interleukins [IL]
• CPC Class Codes: A61K 38/2013 IL-2
• CPC Class Codes: A61K 38/208 IL-12
• CPC Class Codes: A61K 38/2086 IL-13 to IL-16
• CPC Class Codes: A61K 39/0011 Cancer antigens
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/155 Paramyxoviridae, e.g. parainfluenza virus
• CPC Class Codes: A61K 39/35 Allergens
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61K 39/4615 Dendritic cells
• CPC Class Codes: A61K 39/4622 Antigen presenting cells
• CPC Class Codes: A61K 39/4644 Cancer antigens
• CPC Class Codes: A61K 39/464499 Undefined tumor antigens, e.g. tumor lysate or antigens targeted by cells isolated from tumor
• CPC Class Codes: A61K 39/464838 : Viral antigens
• CPC Class Codes: A61K 47/6911 : the form being a liposome
• 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: A61K 9/1272 : with substantial amounts of non-phosphatidyl, i.e. non-acylglycerophosphate, surfactants as bilayer-forming substances, e.g. cationic lipids with cholesterol as the only non-phosphatidyl surfactant A61K9/127; lipids as modifying agent A61K47/543
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/04 : Immunostimulants
• CPC Class Codes: A61P 39/00 : General protective or antinoxious agents
• CPC Class Codes: C12N 2760/18834 : Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

Abstract

This invention relates to a vaccine and a method for immune activation which is effective for eliciting both a systemic, non-antigen specific immune response and a strong antigen-specific immune response in a mammal. The method is particularly effective for protecting a mammal from a disease including cancer, a disease associated with allergic inflammation, an infectious disease, or a condition associated with a deleterious activity of a self-antigen. Also disclosed are therapeutic compositions useful in such a method.

Claims

1. A vaccine comprising:

a. at least one immunogen for vaccinating a mammal;

b. a liposome; and

c. an isolated nucleic acid molecule that does not express said immunogen of (a);

wherein said immunogen and said isolated nucleic acid molecule are complexed to or within said liposome.

2. The vaccine of claim 1, wherein said immunogen comprises at least one epitope that elicits a cellular or humoral immune response in a mammal.

3. The vaccine of claim 1, wherein said immunogen is a peptide.

4. The vaccine of claim 1, wherein said immunogen is selected from the group consisting of a tumor antigen, an infectious disease pathogen antigen, an allergen and a self-antigen.

5. The vaccine of claim 1, wherein said immunogen is a disrupted cell.

6. The vaccine of claim 1, wherein said immunogen is a cell.

7. The vaccine of claim 6, wherein said cell is a pathogenic microorganism.

8. The vaccine of claim 1, wherein said vaccine comprises multiple immunogens.

9. The vaccine of claim 1, wherein said isolated nucleic acid molecule is an oligonucleotide.

10. The vaccine of claim 9, wherein said oligonucleotide contains a CpG motif that is immunogenic in a mammal.

11. The vaccine of claim 9, wherein said oligonucleotide is demethylated.

12. The vaccine of claim 1, wherein said isolated nucleic acid molecule is a plasmid vector that does not contain a gene insert.

13. The vaccine of claim 1, wherein said liposome is a multilamellar vesicle.

14. The vaccine of claim 1, wherein said liposome comprises cationic liposomes.

15. The vaccine of claim 14, wherein said cationic liposomes have been formulated into multilamellar vesicles (MLVs).

16. The vaccine of claim 15, wherein said liposome further comprises cholesterol complexed with said cationic lipids.

17. The vaccine of claim 1, wherein said liposome comprises pairs of lipids selected from the group consisting of DOTMA and cholesterol;

DOTAP and cholesterol;

DOTIM and cholesterol; and

DDAB and cholesterol.

18. The vaccine of claim 1, further comprising a pharmaceutically acceptable excipient.

19. The vaccine of claim 18, wherein said pharmaceutically acceptable excipient is 5-10% sucrose.

20. The vaccine of claim 1, wherein said composition has a nucleic acid to lipid ratio of from about 1:

1 to about 1;

64.

21. The vaccine of claim 1, wherein said isolated nucleic acid molecule encodes a cytokine, said nucleic acid sequence being operatively linked to a transcription control sequence.

22. The vaccine of claim 21, wherein said cytokine is selected from the group consisting of hematopoietic growth factors, interleukins, interferons, immunoglobulin superfamily molecules, tumor necrosis factor family molecules and chemokines.

23. The vaccine of claim 21, wherein said cytokine is an interleukin.

24. The vaccine of claim 21, wherein said cytokine is selected from the group consisting of interleukin-2 (IL-2), interleukin-12 (IL-12), interleukin-18 (IL-18), and interleukin-15 (IL-15).

25. The vaccine of claim 1, wherein said vaccine further comprises at least one cytokine.

26. The vaccine of claim 25, wherein said cytokine is selected from the group consisting of hematopoietic growth factors, interleukins, interferons, immunoglobulin superfamily molecules, tumor necrosis factor family molecules and chemokines.

27. The vaccine of claim 25, wherein said cytokine is selected from the group consisting of interleukin-2 (IL-2), interleukin-12 (IL-12), interleukin-18 (IL-18), and interleukin-15 (IL-15).

28. A method to elicit a systemic, immunogen-specific immune response in a mammal, comprising administering to said mammal a vaccine comprising:

a. at least one immunogen for vaccinating a mammal;

b. a liposome; and

c. an isolated nucleic acid molecule that does not express said immunogen of (a);

wherein said immunogen and said isolated nucleic acid molecule are complexed to or within said liposome.

29. The method of claim 28, wherein said step of administering is by a route selected from the group consisting of intravenous, intraperitoneal, subcutaneous, intradermal, intranodal, intramuscular, transdermal, inhaled, intranasal, rectal, vaginal, urethral, topical, oral, intraocular, intraarticular, intracranial, and intraspinal.

30. The method of claim 28, wherein said step of administering is by a combination of intravenous and intranodal administration.

31. The method of claim 28, wherein said step of administering is by a combination of intraperitoneal and intranodal administration.

32. The method of claim 28, wherein said step of administering is by a combination of intradermal and intranodal administration.

33. The method of claim 28, wherein said immunogen is administered at a dose of from about 1 μ

g per individual mammal to about 1 mg per individual mammal.

34. The method of claim 28, wherein said immunogen is administered at a dose of from about 1 μ

g per individual mammal to about 100 μ

g per individual mammal.

35. The method of claim 28, wherein said immunogen is administered at a dose of from about 1 μ

g per individual mammal to about 10 μ

g per individual mammal.

36. The method of claim 28, wherein administration of said vaccine to said mammal produces a result selected from the group consisting of immunization against said disease or condition and stimulation of effector cell immunity against said disease or condition.