IMMUNOGENIC COMPOSITIONS AND METHODS OF USING THE COMPOSITIONS FOR INDUCING HUMORAL AND CELLULAR IMMUNE RESPONSES

• US 20120328655A1
• Filed: 04/06/2012
• Published: 12/27/2012
• Est. Priority Date: 04/08/2011
• Status: Active Grant

• Current Assignee: Immune Design Corp. (Merck & Co., Inc.)
• Original Assignee: Immune Design Corp. (Merck & Co., Inc.)
• Inventors: Dubensky, Thomas W. Jr., Robbins, Scott H.
• Granted Patent: US 9,044,420 B2
• Time in Patent Office: Days
• US Class Current: 424/231.1
• 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 2039/55566 Emulsions, e.g. Freund's adjuvant, MF59
• CPC Class Codes: A61K 2039/55572 Lipopolysaccharides; Lipid A; Monophosphoryl lipid A
• CPC Class Codes: A61K 2039/70 Multivalent vaccine
• CPC Class Codes: A61K 39/0011 Cancer antigens
• CPC Class Codes: A61K 39/001104 Epidermal growth factor receptors [EGFR]
• CPC Class Codes: A61K 39/001108 Platelet-derived growth factor receptors [PDGFR]
• CPC Class Codes: A61K 39/001109 Vascular endothelial growth factor receptors [VEGFR]
• CPC Class Codes: A61K 39/00111 Hepatocyte growth factor receptor [HGFR or c-met]
• CPC Class Codes: A61K 39/001149 Cell cycle regulated proteins, e.g. cyclin, CDC, CDK or INK-CCR
• CPC Class Codes: A61K 39/001151 p53
• CPC Class Codes: A61K 39/001152 Transcription factors, e.g. SOX or c-MYC
• CPC Class Codes: A61K 39/001153 Wilms tumor 1 [WT1]
• CPC Class Codes: A61K 39/001156 Tyrosinase and tyrosinase related proteinases [TRP-1 or TRP-2]
• CPC Class Codes: A61K 39/001161 Caspases
• CPC Class Codes: A61K 39/001162 Kinases, e.g. Raf or Src
• CPC Class Codes: A61K 39/001164 GTPases, e.g. Ras or Rho
• CPC Class Codes: A61K 39/001168 Mesothelin [MSLN]
• CPC Class Codes: A61K 39/00117 Mucins, e.g. MUC-1
• CPC Class Codes: A61K 39/001171 : Gangliosides, e.g. GM2, GD2 or GD3
• CPC Class Codes: A61K 39/001172 : Sialyl-Thomson-nouvelle antigen [sTn]
• CPC Class Codes: A61K 39/001182 : Carcinoembryonic antigen [CEA]
• CPC Class Codes: A61K 39/001184 : Cancer testis antigens, e.g. SSX, BAGE, GAGE or SAGE
• CPC Class Codes: A61K 39/001186 : MAGE
• CPC Class Codes: A61K 39/001189 : PRAME
• CPC Class Codes: A61K 39/001191 : Melan-A/MART
• CPC Class Codes: A61K 39/001192 : Glycoprotein 100 [Gp100]
• CPC Class Codes: A61K 39/001193 : Prostate associated antigens e.g. Prostate stem cell antigen [PSCA]; Prostate carcinoma tumor antigen [PCTA]; PAP or PSGR
• CPC Class Codes: A61K 39/001194 : Prostate specific antigen [PSA]
• CPC Class Codes: A61K 39/001195 : Prostate specific membrane antigen [PSMA]
• CPC Class Codes: A61K 39/12 : Viral antigens
• CPC Class Codes: A61K 39/245 : Herpetoviridae, e.g. herpes simplex virus
• 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 31/10 : Antimycotics
• CPC Class Codes: A61P 31/12 : Antivirals
• CPC Class Codes: A61P 31/22 : for herpes viruses
• 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 2710/16634 : Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2740/15034 : Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2740/16043 : viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 2810/609 : positive strand RNA viruses
• 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

Compositions and methods are provided herein for improved dual immunization strategies that induce in a subject an immune response that includes a humoral immune response and cellular immune response, both CD4 and CD8 T lymphocyte immune responses, thereby providing a complete adaptive immune response to one or more antigens. The methods described are therefore useful for treating and/or preventing (i.e., reducing the likelihood or risk of occurrence) different diseases, disorders, and conditions such as cancers and infectious diseases for which induction of both a humoral immune response and cellular immune response is desired and beneficial.

Claims

1. A method for inducing an immune response in a subject, the method comprising (a) administering to the subject at least one dose of a first immunogenic composition comprising at least a first immunogen, wherein the at least one dose of a first immunogen is capable of inducing an immune response specific for a first designated antigen;

and (b) administering to the subject at least one dose of a second immunogenic composition comprising a recombinant expression vector comprising a nucleotide sequence that encodes the first immunogen,

thereby inducing an immune response specific for the first designated antigen.

2. The method of claim 1, wherein the first immunogen is a first polypeptide, and said nucleotide sequence encodes a second polypeptide that is different from the first polypeptide.

3. The method of claim 1, wherein (i) the first immunogenic composition further comprises an adjuvant;

(ii) the second composition further comprises an adjuvant;

or (iii) each of the first composition and the second composition further comprises an adjuvant.

4. The method of claim 3, wherein the second immunogenic composition is administered subsequent to administration of the first immunogenic composition.

5. The method of claim 3, wherein the second immunogenic composition is administered prior to administration of the first immunogenic composition.

6. The method of claim 3, wherein the first immunogenic composition and the second immunogenic composition are administered concurrently.

7. The method of claim 3, wherein at least two doses of the first immunogenic composition are administered or wherein at least two doses of the second immunogenic composition are administered.

8. The method of claim 3, wherein (a) two doses;

(b) three doses;

(c) four doses;

or (d) five doses of the first immunogenic composition are administered.

9. The method of claim 8, wherein (a) each dose of the first immunogenic composition is administered prior to administration of the second immunogenic composition;

(b) at least one dose of the first immunogenic composition is administered subsequent to administration of the second immunogenic composition;

(c) at least one dose of the first immunogenic composition is administered concurrently with administration of the second immunogenic composition;

(d) at least one dose of the first immunogenic composition is administered prior to administration of the second immunogenic composition and each of any remaining doses of the first immunogenic composition is administered subsequent to administration of the second immunogenic composition;

or (e) each dose of the first composition is administered concurrently with the second composition.

10. The method of claim 3, wherein the immune response induced by the first immunogen comprises a CD4 T cell immune response specific for the first designated antigen.

11. The method of claim 3, wherein the immune response induced by the first immunogen comprises a CD8 T cell immune response specific for the first designated antigen.

12. The method of claim 3, wherein the first immunogenic composition further comprises a second immunogen, and wherein the recombinant expression vector further comprises a nucleotide sequence that encodes the second immunogen, wherein the second immunogen induces an immune response specific for a second designated antigen.

13. The method of claim 12, wherein the first designated antigen and the second designated antigen are the same.

14. The method of claim 12, wherein the first designated antigen and the second designated antigen are different.

15. The method of claim 3, wherein the recombinant expression vector further comprises a nucleotide sequence that encodes a second immunogen capable of inducing an immune response specific for a second designated antigen.

16. The method of claim 15, wherein the first designated antigen and the second designated antigen are the same.

17. The method of claim 15, wherein the first designated antigen and the second designated antigen are different.

18. The method of claim 12, wherein the immune response induced by the first immunogen comprises a CD4 T cell response specific for the first designated antigen.

19. The method of claim 12, wherein the immune response induced by the second immunogen comprises a CD8 T cell response specific for the second designated antigen.

20. The method of claim 3, wherein the adjuvant is a non-toxic lipid A-related adjuvant.

21. The method of claim 20, wherein the non-toxic lipid A-related adjuvant is glucopyranosyl lipid A (GLA).

22. The method of claim 21, wherein GLA is formulated in a stable oil-in-water emulsion.

23. The method of claim 3, wherein the first designated antigen is (a) a tumor-associated antigen or (b) from an infectious microorganism selected from a virus, a bacterium, a fungus, and a parasite.

24. The method of claim 23, wherein the first designated antigen is a tumor-associated antigen selected from a renal cell carcinoma antigen, a prostate cancer antigen, a mesothelioma antigen, a pancreatic cancer antigen, a melanoma antigen, a breast cancer antigen, a lung cancer antigen, and an ovarian cancer antigen.

25. The method of claim 24, wherein the prostate cancer antigen is prostatic acid phosphatase, prostate specific antigen, NKX3.1, or prostate specific membrane antigen.

26. The method of claim 23, wherein the first designated antigen is from a virus.

27. The method of claim 26, wherein the virus is Herpes Simplex Virus-2 (HSV-2).

28. The method of claim 27, wherein the first designated antigen is HSV-2 UL19 polypeptide or HSV-2 gD polypeptide.

29. The method of claim 12, wherein each of the first designated antigen and the second designated antigen is a tumor-associated antigen.

30. The method of claim 29, wherein each of the first designated antigen and the second designated antigen is selected from a renal cell carcinoma antigen, a prostate cancer antigen, a mesothelioma antigen, a pancreatic cancer antigen, a melanoma antigen, a breast cancer antigen, a lung cancer antigen, and an ovarian cancer antigen.

31. The method according to claim 30, wherein each of the first designated antigen and the second designated antigen is a prostate cancer antigen selected from prostatic acid phosphatase, prostate specific antigen, NKX3.1, or prostate specific membrane antigen.

32. The method of claim 12, wherein each of the first designated antigen and the second designated antigen is an antigen from an infectious microorganism selected from a virus, a bacterium, a fungus, and a parasite.

33. The method of claim 32, wherein the infectious disease organism is a virus.

34. The method of claim 33, wherein the virus is Herpes Simplex Virus-2 (HSV-2).

35. The method of claim 34, wherein at least one of the first designated antigen and the second designated antigen is HSV-2 UL19 polypeptide and the other of the first designated antigen and the second designated antigen is HSV-2 gD polypeptide.

36. The method of claim 3, wherein the recombinant expression vector is selected from a lentiviral vector genome, poxvirus vector genome, vaccinia virus vector genome, adenovirus vector genome, adenovirus-associated virus vector genome, herpes virus vector genome, and an alpha virus vector genome.

37. The method of claim 36, wherein the recombinant expression vector is incorporated into a vector particle.

38. The method of claim 37, wherein the vector particle preferentially delivers the recombinant expression vector to an antigen-presenting cell.

39. The method of claim 38, wherein the antigen-presenting cell is a dendritic cell, preferably a dendritic cell expressing DC-SIGN.

40. The method of claim 37, wherein the vector particle is a lentiviral vector particle that comprises the lentiviral vector genome;

a poxvirus vector particle that comprises the poxvirus vector genome;

a vaccinia virus vector particle that comprises the vaccinia virus vector genome;

an adenovirus vector particle that comprises the adenovirus vector genome;

an adenovirus-associated virus vector particle that comprises the adenovirus-associated virus vector genome;

a herpes virus vector particle that comprises the herpes virus vector genome;

or an alpha virus vector particle that comprises the alpha virus vector genome.

41. The method of claim 40, wherein the vector particle is a lentiviral vector particle that comprises the lentiviral vector genome, and an envelope that preferentially delivers the lentiviral vector particle to a dendritic cell expressing DC-SIGN, optionally an envelope that is a variant of an Arbovirus envelope, or an alphavirus envelope.

42. The method of claim 41, wherein the vector particle is an alphavirus vector particle comprising an envelope that preferentially delivers the alphavirus vector particle to a dendritic cell expressing DC-SIGN.

43. The method of claim 42, wherein the lentiviral vector particle further comprises an envelope comprising a Sindbis virus E2 glycoprotein comprising an amino acid sequence having at least one amino acid change compared to SEQ ID NO:

1, wherein residue 160 of SEQ ID NO;

1 is either absent or an amino acid other than glutamic acid, and wherein the E2 glycoprotein is not a moiety of a fusion protein that comprises Sindbis virus E3 protein.

44. The method of claim 43, wherein the E2 glycoprotein binds to dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN).

45. A preparation comprising (a) a first immunogenic composition that comprises at least a first immunogen capable of inducing an immune response specific for a first designated antigen;

and (b) a second immunogenic composition that comprises a recombinant expression vector that comprises a nucleotide sequence encoding the first immunogen.

46-84. -84. (canceled)