TH94291A - A synergistic vaccine compound, where the adjuvant is a liposome-containing formula containing saponins. And lipopolysaccharides - Google Patents

Abstract

DC60 (09/03/50) This invention provides human dosages of immunogenic mixtures comprising an antigen or an antigenic preparation with an excipient, in which the excipient contains immunoactive saponin fractions derived from the bark of Quillaja Saponaria Molina in liposome and lipopolysaccharide form, where both such saponin and lipopolysaccharide fractions are found in the human dosage at levels below 30 μg. This invention also provides an excipient mixture in appropriate volumes for human dosages between 1 and 30 μg of lipopolysaccharide and between 1 and 30 μg of the liposomed immunoactive saponin fraction. This invention provides human dosages of immunogenic mixtures comprising an antigen or an antigenic preparation with an excipient, in which the excipient contains the aforementioned fractions. Immunobacterial saponins derived from the bark of Quillaja Saponaria Molina are available in liposome and lipopolysaccharide forms, with both saponin and lipopolysaccharide fractions found at human doses below 30 mcg. This invention also provides an excipient mixture in appropriate volumes for human doses between 1 and 30 mcg of lipopolysaccharide and between 1 and 30 mcg of the liposome-formed immunoactive saponin fraction.

Claims (85)

1. The human dosage of immunogenic mixtures containing an antigen or an antigenic preparation combined with an excipient containing an immunoactive saponin sequence derived from the bark of Quillaja Saponaria Molina in the form of liposomes and lipopolysaccharides, where both the saponin and lipopolysaccharide sequences are found at human dosages below 30 µg. 2. Human dosage of the immunogenic mixture according to claim 1, where the mixture and excipients also contain sterols, with a saponin:sterol ratio of 1:1 to 1:100 weight/weight. 3. Human dosage of the immunogenic mixture according to claim 2, where the saponin:sterol ratio is from 1:1 to 1:10 weight/weight. 4. Human dosage of the immunogenic mixture according to claim 2, where the saponin:sterol ratio is from 1:1 to 1:5 weight/weight. 5. The human dosage of any one of the immunogenic mixtures under claims 1 through 4, where the immunogenic saponin fraction is QS21. 6. The human dosage of any one of the immunogenic mixtures under claims 2 through 5, where such sterol is cholesterol. 7. The human dosage of the immunogenic mixture under one of the preceding claims, where such lipopolysaccharide is a derivative of lipid A. 8. The human dosage of the immunogenic mixture pursuant to claim 7, where the derivative of lipid A is 3D-MPL. 9. The human dosage of the immunogenic mixture as per claim 7 or 8, where the ratio of QS21 : 3D-MPL is 1 : 1. 10. The human dosage of any one of the immunogenic mixtures under claims 1 through 9 shall also include a carrier. 11. The human dosage of the immunogenic mixture as per one of the prior claims, where such lipopolysaccharide is found in amounts of 1-30 micrograms. 12. The human dosage of the immunogenic mixture under claim 11, where the lipopolysaccharide is found at a quantity of 25 micrograms. 13. The human dosage of the immunogenic mixture under claim 11, where the lipopolysaccharide is found in amounts of 1-15 micrograms. 14. The human dosage of the immunogenic mixture under claim 13, where the lipopolysaccharide is found at a quantity of 10 micrograms. 15. The human dosage of the immunogenic mixture under claim 13, where the lipopolysaccharide is found at a quantity of 5 micrograms. 16. The human dosage of any one of the immunogenic mixtures under claims 11-15, where such lipopolysaccharide is a derivative of lipid A. 17. The human dosage of the immunogenic mixture pursuant to claim 16, where the aforementioned lipid derivative A is 3D-MPL. 18. The human dosage of the mixture as per one of the prior claims where such saponins are found in amounts of 1-25 micrograms. 19. The human dosage of the mixture under claim 18, where the saponin is found at 25 micrograms. 20. The human dosage of the mixture under claim 18, where the saponin is found in amounts of 1-10 micrograms. 21. The human dosage of the mixture under claim 20, where the saponin is found at a quantity of 10 micrograms. 22. The human dosage of the mixture under claim 20, where the saponin is found at a quantity of 5 micrograms. 23. The human dosage of any one of the combinations of claims 18-22, where the immunogenic saponin fraction is QS21. 24. The human dosage of the mixture as claimed in any of the preceding claims, where such human dosage is between 0.5 and 1.5 ml. 25. The human dosage of the mixture as claimed in claim 24, where the said human dosage is 0.5 ml. 26. The human dosage of the mixture as claimed in claim 24, where the said human dosage is 0.7 ml. 27. The human dosage of the mixture as claimed in claim 24, where such human dosage is 1.0 ml. 28. A mixture of excipients in appropriate volumes for human dosage comprising between 1 and 30 micrograms of lipopolysaccharide and between 1 and 30 micrograms of immunomodulatory saponin fraction in liposome form. 29. A mixture of excipients as per claim 28, where the lipopolysaccharide is lipid derivative A. 30. A mixture of additives as per claim 29, whereby the lipid derivative A is 3D-MPL. 31. A mixture of excipients as per any of the claims 28-30, where the sequence of the immunoactive saponin is QS21. 32. A mixture of excipients as per any of Claims 28-31, where the said lipopolysaccharide and the immunogenic saponin fraction are present in the excipient mixture in equal amounts. 33. A mixture of excipients as specified in any of the claims in Patents 28-32, where the appropriate volume of such human dose is 250 microliters. 34. A mixture of excipients as specified in any of the claims 28-32, where the appropriate volume of such human dose is 360 microliters. 35. A mixture of any of the excipients listed in Claims 28-34, where such lipopolysaccharide is present in the amount of 25 mcg. 36. A mixture of any of the excipients listed in Claims 28-34, where such lipopolysaccharide is present in the amount of 10 micrograms. 37. A mixture of any of the excipients listed in Claims 28-34, where such lipopolysaccharide is present in the amount of 5 micrograms. 38. A mixture of any of the excipients listed in Claims 28-37, in which an immunomodulatory saponin is present at a concentration of 25 mcg. 39. A mixture of any of the excipients listed in Claims 28-37, in which an immunomodulatory saponin is present at a concentration of 10 mcg. 40. A mixture of excipients as per any of Claims 28-37, in which immunomodulatory saponins are present at a concentration of 5 mcg. 41. An immunogenic mixture containing the influenza virus or its antigenic preparation together with an excipient mixture containing immunogenic saponins in liposome form. 42. An immunogenic mixture pursuant to claim 41, which includes lipid derivative A. 43. An immunogenic mixture pursuant to claim 42, whereby the lipid derivative A is 3D-MPL. 44. The use of (a) the antigen or its antigenic preparation and (b) the adjuvants as defined in any of Reservations 1 through 43 to produce at least one or at least two or all of the following in human immunogenic mixtures for induction in humans: (i) an enhanced CD4 T-cell immune response to such antigen or its antigenic preparation; (ii) an enhanced humoral immune response to such antigen or its antigenic preparation; (iii) an enhanced B recognition cell response to such antigen or its antigenic preparation. 45. A method of administering a vaccine containing an antigen or antigenic mixture and adjuvants as defined in any of Reservices 1 through 43 to individuals or populations requiring it. 46. The use or methods under claims 44 or 45 in elderly human beings or in persons or human populations recognized as immune. 47. The use or method as described in any of the claims 44 through 46, whereby the administration of such immunogenic mixture induces both an enhanced CD4 T cell immune response and an enhanced B cell recognition response. 48. The use or method according to any of the claims 44 through 47 where the immune response of such CD4 T cells involves the induction of a cross-sensitive CD4-assisted T-response. 49. The use or method under any of the claims 44 through 48 where such a humoral immune response is associated with the induction of a cross-reacting humoral response. 50. The use or method as specified in any of the claims under Articles 44 through 49, where the target population is elderly persons over 65 years of age. 51. The use or method under any of the claims 44 through 50 for the prevention of infection or disease caused by a pathogen which is a variant of the pathogen to which the immunogenic antigen in the mixture is derived. 52. The use or method under any of the claims 44 through 50 for the prevention of infection or disease caused by a pathogen which is a variant of the pathogen, which includes an antigen that is a variant of the antigen in an immunogenic mixture. 53. The use or method under claims 51 or 52 where the post-revaccination immune response is any one or two or all of the following: an enhanced CD4 response to the antigen or its antigenic preparation, a humoral response, or an enhanced B memory cell response. 54. The use or method as per claims 51 or 52, where protection is assessed by the body temperature of an infected person or population. 55. A mixture, use, or method as described in any of the claims 1 through 54, whereby the immunogenic mixture contains an antigen with a CD4 T cell epitope. 56. A mixture, use, or method as described in any of the claims 1 through 54, whereby the immunogenic mixture contains an antigen with B epitope cells. 57. The use of antigens in the production of immunogenic mixtures for the replenishment of vaccines to individuals who have previously received a vaccine with the antigen or antigenic mixture or its fragments or variants and adjuvants as defined in any of Reservices 1 through 43. 58. Use under claim 57 whereby the revaccination antigen is combined with a common CD4 T cell epithelial antigen or antigenic mixture used for a previous vaccination. 59. Use under claim 57 or 58 where the antigen or antigenic mixture for booster vaccination has been added. 60. Use under claim 59 where the additive is as defined in any one of claims 1 through 43. 61. The human dosage of any immunogenic mixture claimed under any of the claims 1-27 for medical use. 62. Mixtures, uses, or methods as per any of Claims 1 through 61, where the antigen or antigenic preparation is selected from a list comprising influenza virus, HPV, CMV, VZV, Streptococcus pneumoniae, Plasmodium falciparum, respiratory syncytial virus (RSV). 63. The mixture, use, or method under claim 62, whereby such influenza antigens are selected from a list containing isolated influenza viruses, purified whole influenza viruses, influenza virus subunits, and their antigenic preparations. 64. Mixtures, uses, or methods under claim 63 where the influenza virus or its antigenic preparations are derived from at least two influenza virus strains. 65. Mixtures, uses, or methods under claim 64 where the influenza virus or its antigenic preparations are derived from at least three influenza virus strains. 66. Mixtures, uses, or methods under claim 65 where the influenza virus or its antigenic preparations are derived from at least four influenza virus strains. 67. Any combination of any of the claims 63 through 66 where at least one strain of such influenza virus or its antigenic preparation is associated with or has the potential to be associated with a pandemic. 68. Mixtures, uses, or methods under claim 67 where at least two strains of such influenza virus or its antigenic preparations are associated with or have the potential to be associated with a pandemic. 69. Mixtures, uses, or methods under claim 68 where at least three strains of such influenza virus or its antigenic preparations are associated with or have the potential to be associated with a pandemic. 70. A mixture, use, or method as provided in under any of the claims 67 through 69, where at least one, at least two, or at least three of the following circulating influenza virus strains are selected from a list comprising: H5N1, N9N2, H7N7, and H2N2. 71. Mixtures, uses, or methods as specified in any of Claims 62 through 70 where such influenza virus or its antigenic preparations contain between 1 and 15 micrograms of HA per influenza strain. 72. Mixtures, uses, or methods as specified in any of the claims 62 through 70 where the influenza virus or its antigenic preparation contains less than 15 micrograms HA per influenza strain. 73. Mixtures, uses, or methods as per claims 71 or 72 where such influenza virus or its antigenic preparations contain between 2.5 and 7.5 micrograms of HA per strain. 74. The use or method under any of the claims 51 through 53 where the influenza virus, or its antigenic preparation for revaccination, comes from at least two different influenza strains. 75. The use or method under claim 74 where the influenza virus or its antigenic preparation for revaccination comes from at least three different influenza strains. 76. The use or method under any of Claims 51 through 53 whereby the influenza virus or its antigenic preparation for revaccination contains at least one influenza strain that is associated with or has the potential to be associated with a pandemic. 77. The use or method as per claim 76, whereby the pandemic strains are selected from the list comprising: H5N1, N9N2, H7N7, and H2N2. 78. The use or method as per any of Claims 51 to 53 and 74 to 77 where the initial vaccination is given with an influenza mixture containing an influenza strain that is potentially capable of causing a pandemic and a booster vaccination is given with an influenza mixture containing a circulating pandemic strain. 79. The use or method as specified in any of the claims 51 to 53 and 74 to 78 where such influenza antigen or its antigenic preparation contains less than 15 micrograms HA antigen per dose. 80. The use or method under any of the claims 62 through 79 where the influenza antigen or its antigenic preparation is derived from an egg or derived from a cell culture. 81. The mixture, use, or method under claim 62 where the HPV antigen is associated with cancer or genital warts. 82. The mixture, use, or method as per claim 81, where the cancer-associated HPVs are HPV type 16 and/or HPV type 18. 83. Mixtures, uses, or methods as per claim 82, where one or more additional antigens from the carcinogenic HPV types are used with HPV 16 and/or 18 antigens selected from the following HPV types: HPV 31, 45, 33, 58, and 52. 84. Mixtures, uses, or methods as per claims 82 or 83 where the antigen is in the form of viral-like particles (VLPs). 85. Mixtures, uses, or methods as per claim 84, where VLPs are L1 VLPs.