Insect cells or fractions as adjuvant for antigens

• US 6,224,882 B1
• Filed: 11/07/1997
• Issued: 05/01/2001
• Est. Priority Date: 11/07/1997
• Status: Expired due to Term

• Current Assignee: Merial Limited (C.H. Boehringer Sohn AG & Co. KG)
• Original Assignee: Protein Sciences Corporation (Sanofi )
• Inventors: Smith, Gale Eugene, Voznesenski, Andrei Igorevitch, DeBartolomeis, James
• Primary Examiner(s): Eyler, Yvonne
• Assistant Examiner(s): SUN HOFFMAN, LIN
• Application Number:
  US08/965,698
• Time in Patent Office: 1,271 Days
• Field of Search: 424/279.1, 424/278.1, 424/93.1, 424/184.1
• US Class Current: 424/279.1
• CPC Class Codes: A61K 2039/55588 Adjuvants of undefined constitution
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/145 Orthomyxoviridae, e.g. influenza virus
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: C12N 2760/16134 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

Abstract

Disclosed and claimed is an adjuvant for immunogenic, immunological, antigenic or vaccine compositions. The adjuvant is composed of insect cells or fractions thereof. Disclosed and claimed are also methods for preparing and using the adjuvant and compositions containing the adjuvant. Advantageously, a recombinant baculovirus containing DNA encoding and expressing an epitope of interest or antigen can be infected into insect cells such as insect cells derived from a Lepidopteran species such as S. frugiperda for expression, and the infected insect cells or a fraction thereof can be used with the expressed epitope of interest or antigen as an inventive antigen or in an inventive immunological, antigen or vaccine composition.

Claims

1. In an immunogenic, immunological or vaccine composition comprising at least one epitope of interest or antigen wherein the improvement comprises the composition comprising a first component comprising the epitope of interest or antigen isolated from a source other than insect cells and a second component comprising an adjuvant comprising insect cells or a fraction thereof, wherein the insect cells are obtainable from an insect species which is not biting and/or from an insect species wherein hypersensitivity to the insect cell antigens is low or absent in human and animal species and/or from an insect species which is non-toxic, non-pyrogenic, non-tumorgenic, contains no known retroviruses or other human or animal viruses, mycoplasma or other pathogens.

2. The composition of claim 1 wherein the at least one epitope of interest or antigen comprises at least one isolated epitope of interest.

3. The composition of claim 1 wherein the at least one epitope of interest or antigen comprises at least one isolated antigen.

5. The composition of any one of claim 2, 3, or 4 wherein the cells are obtainable from infection of the cells by an insect virus.

6. The composition of claim 5 wherein the insect virus is a recombinant insect virus.

7. The composition of claim 5 wherein the insect virus is a baculovirus.

8. The composition of any one of claim 2, 3, or 4 wherein the insect cells are whole and/or intact.

9. The composition of any one of claim 2, 3, or 4 wherein the insect cells are disrupted.

10. The composition of claim 9 wherein the insect cells are disrupted by mechanical or chemical or both chemical and mechanical means.

11. The composition of claim 5 wherein the virus is inactivated and/or removed.

12. The composition of claim 11 wherein the virus is chemically inactivated.

13. The composition of claim 12 wherein the virus is inactivated by treatment with formaldehyde or treatment with at least one detergent.

14. The composition of any one of claim 1, 2, 3, or 4 wherein the adjuvant includes an insect cell membrane fraction.

16. A method for eliciting an immunological or protective response in an animal or human comprising administering to the animal or human a composition as claimed in any one of claim 1, 15 or 4.

17. The composition of any one of claim 1, 2, 3, or 4 wherein the adjuvant insect cells are obtainable from a Lepidopteran species.

18. The composition of any one of claim 1, 2, 3, or 4 wherein the adjuvant insect cells are obtainable from Spodoptera frugiperda.

19. The composition of any one of claim 1, 2, 3, or 4 wherein the adjuvant insect cells are from the Sf9 cell line.

20. The composition of claim 1 wherein the adjuvant insect cells are obtainable from infection of the cells by an insect virus.

21. The composition of claim 20 wherein the insect virus is a recombinant insect virus.

22. The vaccine composition of claim 20 wherein the insect virus is a baculovirus.

23. The composition of claim 1 wherein the adjuvant insect cells are whole and/or intact.

24. The composition of claim 1 wherein the adjuvant insect cells are disrupted.

25. The composition of claim 24 wherein the adjuvant insect cells are disrupted by mechanical or chemical or both chemical and mechanical means.

48. The method of claim 16 wherein the adjuvant insect cells are obtainable from a Lepidopteran species.

49. The method of claim 48 wherein the adjuvant insect cells are disrupted by mechanical or chemical or both chemical and mechanical means.

61. The method of claim 16 wherein the adjuvant insect cells are obtainable from infection of the cells by an insect virus.

62. The method of claim 61 wherein the insect virus is a baculovirus or a recombinant baculovirus.

63. The method of claim 16 wherein the adjuvant insect cells are whole and/or intact or are disrupted.

64. The method of claim 63 wherein the adjuvant insect cells are disrupted by mechanical or chemical or both chemical and mechanical means.

4. An immunogenic, immunological or vaccine composition comprising at least one immunologically active component, wherein said immunologically active component consists of an epitope of interest or antigen and as an immunogenicity-enhancing adjuvant, insect cells or a fraction thereof, wherein the insect cells are obtainable from an insect species which is not biting and/or from an insect species wherein hypersensitivity to the insect cell antigens is low or absent in human and animal species and/or from an insect species which is non-toxic, non-pyrogenic, non-tumorgenic, contains no known retroviruses or other human or animal viruses, mycoplasma or other pathogens.

15. An immunological, immunogenic or vaccine composition comprising at least one epitope of interest isolated from a source other than insect cells and a separately added adjuvant, wherein the adjuvant comprises insect cells or a fraction thereof, wherein the cells are obtainable from an insect species which is not biting and/or from an insect species wherein hypersensitivity to the insect cell antigens is low or absent in human and animal species and/or from an insect species which is non-toxic, non-pyrogenic, non-tumorgenic, contains no known retroviruses or other human or animal viruses, mycoplasma or other pathogens.

50. The immunological, immunogenic or vaccine composition of claim 15 wherein the adjuvant insect cells are obtainable from a Lepidopteran species.

51. The immunological, immunogenic or vaccine composition of claim 15 wherein the adjuvant insect cells are obtainable from Spodoptera frugiperda.

52. The immunological, immunogenic or vaccine composition of claim 15 wherein the adjuvant insect cells are from the Sf9 cell line.

53. The immunological, immunogenic or vaccine composition of claim 15 wherein the adjuvant insect cells are obtainable from infection of the cells by an insect virus.

54. The immunological, immunogenic or vaccine composition of claim 53 wherein the insect virus is a recombinant insect virus.

55. The immunological, immunogenic or vaccine composition of claim 53 wherein the insect virus is a baculovirus.

56. The immunological, immunogenic or vaccine composition of claim 15 wherein the adjuvant insect cells are whole and/or intact.

57. The immunological, immunogenic or vaccine composition of claim 15 wherein the adjuvant insect cells are disrupted.

58. The immunological, immunogenic or vaccine composition of claim 57 wherein the adjuvant insect cells are disrupted by mechanical or chemical or both chemical and mechanical means.

26. A kit for the preparation of an immunogenic, immunological or vaccine composition comprising at least one epitope of interest or antigen and an adjuvant, wherein the adjuvant comprises insect cells or a fraction thereof, wherein the cells are obtainable from an insect species which is not biting and/or from an insect species wherein hypersensitivity to the insect cell antigens is low or absent in human and animal species and/or from an insect species which is non-toxic, non-pyrogenic, non-tumorgenic, contains no known retroviruses or other human or animal viruses, mycoplasma or other pathogens;

said kit comprising the epitope of interest or antigen in a first container, and the adjuvant in a second container, and optionally instructions for admixing the epitope of interest or antigen and the adjuvant and/or for administration of the composition; and

wherein optionally the containers are in a package.

27. The kit of claim 26 wherein the adjuvant insect cells are obtainable from a Lepidopteran species.

28. The kit of claim 26 wherein the adjuvant insect cells are obtainable from Spodoptera frugiperda.

29. The kit of claim 26 wherein the adjuvant insect cells are from the Sf9 cell line.

30. The kit of claim 26 wherein the adjuvant insect cells are obtainable from infection of the cells by an insect virus.

31. The kit of claim 30 wherein the insect virus is a recombinant insect virus.

32. The kit of claim 30 wherein the insect virus is a baculovirus.

33. The kit of claim 31 wherein the recombinant insect virus is a recombinant baculovirus comprising at least one exogenous coding nucleic acid for an epitope of interest or antigen.

34. The kit of claim 26 wherein the adjuvant insect cells are whole and/or intact.

35. The kit of claim 26 wherein the adjuvant insect cells are disrupted.

65. The kit of claim 35 wherein the adjuvant insect cells are disrupted by mechanical or chemical or both chemical and mechanical means.

36. A method for enhancing the immunogenicity of an isolated epitope of interest or antigen comprising administering the isolated epitope of interest or isolated antigen with or in conjunction with an adjuvant, wherein the adjuvant comprises insect cells or a fraction thereof, wherein the cells are obtainable from an insect species which is not biting and/or from an insect species wherein hypersensitivity to the insect cell antigens is low or absent in human and animal species and/or from an insect species which is non-toxic, non-pyrogenic, non-tumorgenic, contains no known retroviruses or other human or animal viruses, mycoplasma or other pathogens.

37. The method as claimed in claim 36 further comprising preparing the adjuvant by a method comprising isolating insect cells, and optionally infecting the cells with an insect virus, and optionally disrupting and/or fractionating the cells, and optionally inactivating the virus.

38. The method of claim 36 wherein the adjuvant insect cells are obtainable from a Lepidopteran species.

39. The method of claim 36 wherein the adjuvant insect cells are obtainable from Spodoptera frugiperda.

40. The method of claim 36 wherein the adjuvant insect cells are from the Sf9 cell line.

41. The method of claim 36 wherein the adjuvant insect cells are obtainable from infection of the cells by an insect virus.

42. The method of claim 41 wherein the insect virus is a recombinant insect virus.

43. The method of claim 41 wherein the insect virus is a baculovirus.

44. The method of claim 42 wherein the recombinant insect virus is a recombinant baculovirus comprising at least one exogenous coding nucleic acid for an epitope of interest or antigen.

45. The method of claim 36 wherein the adjuvant insect cells are whole and/or intact.

46. The method of claim 36 wherein the adjuvant insect cells are disrupted.

47. The method of claim 46 wherein the adjuvant insect cells are disrupted by mechanical or chemical or both chemical and mechanical means.

59. A method for preparing a composition comprising at least one isolated epitope of interest or antigen and as an immunogenicity-enhancing adjuvant insect cells or a fraction thereof, wherein the insect cells are obtainable from an insect species which is not biting and/or from an insect species wherein hypersensitivity to the insect cell antigens is low or absent in human and animal species and/or from an insect species which is non-toxic, non-pyrogenic, non-tumorgenic, contains no known retroviruses or other human or animal viruses, mycoplasma or other pathogens, said method comprising infecting insect cells with a recombinant insect virus comprising at least one exogenous coding nucleic acid molecule for the epitope of interest or antigen and expressing the epitope of interest or antigen, isolating insect cells, isolating the epitope of interest or antigen, and optionally disrupting and/or fractionating the cells, and optionally inactivating the virus.

60. A method for preparing a composition comprising at least one isolated epitope of interest or antigen and as an immunogenicity-enhancing adjuvant insect cells or a fraction thereof, wherein the insect cells are obtainable from an insect species which is not biting and/or from an insect species wherein hypersensitivity to the insect cell antigens is low or absent in human and animal species and/or from an insect species which is non-toxic, non-pyrogenic, non-tumorgenic, contains no known retroviruses or other human or animal viruses, mycoplasma or other pathogens, said method comprising admixing the adjuvant and the at least one epitope of interest or antigen.