Nucleic acid vaccine compositions having a mammalian CD80/CD86 gene promoter driving antigen expression

• US 20050226846A1
• Filed: 12/31/2003
• Published: 10/13/2005
• Est. Priority Date: 11/03/1999
• Status: Abandoned Application

• Current Assignee: Powderject Research Limited (Pfizer Inc.)
• Original Assignee: Powderject Research Limited (Pfizer Inc.)
• Inventors: Umlauf, Scott
• Application Number:
  US10/748,124
• Publication Number:
  US 20050226846A1
• Time in Patent Office: Days
• US Class Current: 424/93.100
• 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 2039/55522 Cytokines; Lymphokines; Interferons
• 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 38/177 Receptors; Cell surface antigens; Cell surface determinants
• CPC Class Codes: A61K 38/18 Growth factors; Growth regulators
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/292 Serum hepatitis virus, hepatitis B virus, e.g. Australia antigen
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C12N 15/895 using biolistic methods
• 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 2730/10134 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

Abstract

Polynucleotides encoding at least one immunizing antigen whose expression is controlled by a promoter derived from a gene encoding a co-stimulatory molecule are provided. The polynucleotides may also encode adjuvants. Compositions comprising at least one immunizing agent and at least one cytokine that enhance dendritic cell stimulation and/or survival are also provided. Methods for eliciting an immune response against the immunizing agent are also provided. The method includes the steps of administering the polynucleotides and, optionally, co-administering an adjuvant.

Claims

1. A polynucleotide comprising a first promoter derived from a gene encoding a co-stimulatory molecule and a first sequence encoding at least one antigen wherein said first sequence is operably linked to said first promoter.

2. The polynucleotide of claim 1, wherein the promoter is derived from a CD80 (B7-1) gene.

3. The polynucleotide of claim 1, wherein the promoter is derived from a CD86 (B7-2) gene.

4. The polynucleotide of claim 1, further comprising a second sequence encoding at least one cytokine operably linked to the first promoter.

5. The polynucleotide of claim 4, wherein the cytokine is selected from the group consisting of CD40 ligand (CD40L), tumor-necrosis factor-related activation-induced cytokine (TRANCE) and Flt3 ligand.

6. The polynucleotide of claim 1, further comprising a second sequence encoding at least one cytokine and a second promoter, wherein the second sequence is operably linked to the second promoter.

7. The polynucleotide of claim 6, wherein said second promoter is a constitutive promoter.

8. The polynucleotide of claim 6, wherein the cytokine is selected from the group consisting of CD40 ligand (CD40L), tumor-necrosis factor-related activation-induced cytokine (TRANCE) and Flt3 ligand.

9. A core carrier coated with a polynucleotide according to claim 1.

10. The carrier of claim 9, wherein the carrier is comprised of gold.

11. A pharmaceutical composition, comprising a polynucleotide according to claim 1 and a pharmaceutically acceptable excipient.

12. The pharmaceutical composition of claim 11, further comprising a cytokine.

13. The pharmaceutical composition of claim 12, wherein the cytokine is selected from the group consisting of CD40L, tumor-necrosis factor-related activation-induced cytokine (TRANCE) and Flt3 ligand.

14. A method for eliciting an immune response in a vertebrate subject, said method comprising:

(a) providing a nucleotide sequence encoding an antigen operably linked to a promoter derived from a gene encoding a co-stimulatory molecule, said promoter capable of directing the expression of said antigen in the, subject; and

(b) administering the nucleotide sequence to the subject, whereby the antigen is expressed in an amount sufficient to elicit an immune response.

15. The method of claim 14, wherein the co-stimulatory molecule is CD80 or CD86.

16. The method of claim 14, further comprising the step of administering at least one cytokine to the subject.

17. The method of claim 16, wherein the cytokine is administered as a polynucleotide encoding the at least one cytokine.

18. The method of claim 16, wherein the cytokine is administered as a protein.

19. The method of claim 16, wherein the cytokine is selected from the group consisting of CD40L, tumor-necrosis factor-related activation-induced cytokine (TRANCE) and Flt3 ligand (flt-3L).

20. A method for eliciting an immune response in a vertebrate subject, said method comprising:

(a) providing a core carrier particle coated with a nucleotide sequence encoding at least one antigen, said nucleotide sequence operably linked to a promoter derived from a gene encoding a co-stimulatory factor, wherein said promoter is capable of driving expression of the antigen-encoding sequence in the subject; and

(b) administering the coated particle to the subject using a particle-mediated transdermal delivery technique, whereby the antigen is expressed in an amount sufficient to elicit an immune response.

21. The method of claim 20 wherein the core carrier particle is a gold particle.

22. The method of claim 20, wherein the nucleotide sequence further comprises a sequence encoding a cytokine selected from the group consisting of TRANCE, CD40L and flt-3L.

23. The method of claim 20, further comprising administering to the subject a cytokine selected from the group consisting of TRANCE, CD40L and flt-3L.

24. The method of claim 20, wherein step (b) is repeated to provide a prime and a booster administration.

25. The method of claim 24, wherein the core carrier particle is a gold particle.

26. A vaccine composition comprising:

(a) an expression vector comprising a polynucleotide encoding at least one antigen; and

(b) at least one cytokine selected from the group consisting of CD40 ligand (CD40L), tumor-necrosis factor-related activation-induced cytokine (TRANCE) and Flt3 ligand (flt-3L).

29. The vaccine composition according to claim 26, wherein the polynucleotide and/or the at least one cytokine is coated onto a core carrier.

32. A method for eliciting an immune response in a vertebrate subject, said method comprising:

(a) providing a vaccine composition according to claim 26;

and

(b) administering the composition to the subject, whereby the antigen is expressed in an amount sufficient to elicit an immune response.

35. A method for eliciting an immune response in a vertebrate subject, said method comprising:

(a) providing a vaccine composition according to claim 29;

and

(b) administering the composition of step (a) to the subject using a particle-mediated delivery technique.

36. The method of claim 35, wherein the core carrier is a gold particle.

37. The method of claim 35, wherein step (b) is repeated to provide a prime and a booster administration.

27. A vaccine composition comprising:

(a) at least one peptide antigen; and

(b) an expression vector comprising a polynucleotide encoding at least one cytokine selected from the group consisting of CD40 ligand (CD40L), tumor-necrosis factor-related activation-induced cytokine (TRANCE) and Flt3 ligand (flt-3L).

30. The vaccine composition according to claim 27, wherein the polynucleotide and/or the at least one peptide antigen is coated onto a core carrier.

33. A method for eliciting an immune response in a vertebrate subject, said method comprising:

(a) providing a vaccine composition according to claim 27;

and

(b) administering the composition to the subject in an amount sufficient to elicit an immune response.

38. A method for eliciting an immune response in a vertebrate subject, said method comprising:

(a) providing a vaccine composition according to claim 30;

and

(b) administering the composition of step (a) to the subject using a particle-mediated delivery technique.

39. The method of claim 38, wherein step (b) is repeated to provide a prime and a booster administration.

28. A vaccine composition comprising:

(a) at least one peptide antigen; and

(b) at least one cytokine selected from the group consisting of CD40 ligand (CD40L), tumor-necrosis factor-related activation-induced cytokine (TRANCE) and Flt3 ligand (flt-3L).

31. The vaccine composition according to claim 28, wherein the at least one peptide antigen and/or the at least one cytokine is coated onto a core carrier.

34. A method for eliciting an immune response in a vertebrate subject, said method comprising:

(a) providing a vaccine composition according to claim 28;

and

(b) administering the composition to the subject in an amount sufficient to elicit an immune response.

40. A method for eliciting an immune response in a vertebrate subject, said method comprising:

(a) providing a vaccine composition according to claim 31;

and

(b) administering the composition of step (a) to the subject using a particle-mediated delivery technique.

41. The method of claim 40, wherein step (b) is repeated to provide a prime and a booster administration.