TH97935A - Immunogeneic composition Which includes Streptococcuspneumoniae capsular saccharides - Google Patents

Abstract

DC60 (14/03/2007) This invention discloses an immunogenic mixture consisting of S.pneumoniae capsulersaccharide conjugates from serotypes 19A and 19F, where 19A is conjugated to the first bacteryltoxoid and 19F is conjugated to the second bacteryltoxoid. It also discloses a vaccine, methods for vaccine production, and vaccine use. Abstract revised 18/09/2015. This invention discloses an immunogenic mixture consisting of S.pneumoniae capsulersaccharide conjugates from serotypes 19A and 19F, where 19A is conjugated to the first bacteryltoxoid and 19F is conjugated to the second bacteryltoxoid. It also discloses a vaccine, methods for vaccine production, and vaccine use. -------------------------------------------------------- Abstract This invention discloses... The immunogenic mixture, comprising S.pneumoniae capsulersaccharide conjugates from serotypes 19A and 19F (where 19A is conjugated to the first bacteryltoxoid and 19F to the second bacteryltoxoid), also revealed the vaccine, the method for vaccine production, and the use of the vaccine.

Claims (133)

Revised 18/09/2015 1. Immunogenic composition consisting of capsulersaccharide conjugates of S. pneumoniae from serotypes 19A and 19F, where 19A is conjugated with the first bacterlotoxoid and 19F is conjugated with the second bacterlotoxoid, and further composed of conjugates of S. pneumonia capsulersaccharides 4, 6B, 9V, 14, 18C, 22F, and 23F. 2. Immunogenic composition of claim 1, where the first bacterlotoxoid is 3. An immunogenic component of claim 1 or 2 that also contains conjugates of S. pneumonia capsulersaccharides 1, 5, and 7F. 4. An immunogenic component of any one of claims 1-3 that also contains S. pneumonia capsulersaccharide 3 conjugate. 5. An immunogenic component of any one of claims 1-4 that also contains S. pneumonia capsulersaccharide 6A conjugate. 6. An immunogenic component of any preceding claim that also contains one or more conjugated or unconjugated S. pneumonia proteins. 7. An immunogenic mixture of claim 74 or 75 where one protein... Or more of the following S.pneumoniae are selected from the polyhistidine triad family (PhtX), the choline-binding protein family (CbpX), truncated CbpX (trancates), the LytX family, truncated LytX, truncated CbpX-LytX chimeric proteins, detoxified pneumolysin (Ply), PspA, PsaA, Sp128, Sp101, Sp130, Sp125, and Sp133. 8. An immunogenic component of claim 6 or 7 that includes the PhtX protein. 9. An immunogenic component of any of the preceding claims that also includes... 10. An adjuvant. A vaccine consisting of an immunogenic component as provided for in any of the claims in Clauses 1 through 9 and a pharmaceutically acceptable filler. 11. A procedure for the manufacture of a vaccine as provided for in Clause 10, consisting of a procedure for combining the immunogenic component of any one of the claims in Clauses 1 through 9 with a pharmaceutically acceptable filler. 12. The use of an immunogenic component or a vaccine as provided for in any of the claims in Clauses 1 through 9, or a vaccine as provided for in Clause 10, in the manufacture of drugs for the treatment or prevention of diseases caused by Streptococcus pneumoniae infection. ---------------------------------------------------------------------------- Claims 1. An immunogenic mixture containing capsule saccharide conjugates of S. pneumoniae from serotypes 19A and 19F, where 19A is conjugated with the first bacterium toxoid and 19F is conjugated with the second bacterium toxoid. 2. An immunogenic mixture of claim 1, where the first bacteryl toxoid is a protein distinct from the second bacteryl toxoid. 3. An immunogenic mixture of claim 1 or 2 is selected from a group consisting of tetanus toxoid, dipteria toxoid, CRM197 pertussis toxoid, bacterial cytolysin, and pneumolisin. 4. An immunogenic mixture of one of the claims in clauses 1-3, whereby a second bacterial toxoid is selected from a group consisting of tetanus toxoid, dipteria toxoid, CRM197, pertussis toxoid, bacterial cytolysin, and pneumolisin. 5. An immunogenic mixture of any one of the claims in clauses 1-4, where the first bacterium toxoid is pneumolysin. 6. An immunogenic mixture of any one of the claims in clauses 1-5, where the second bacterial toxoid is dipteria toxoid. 7. An immunogenic mixture of one of the claims in clauses 1-6, which also includes the S. pneumoniae conjugate saccharides 4, 6B, 9V, 14, 18C, and 23F. 8. An immunogenic mixture of one of the claims in clauses 1-7, which also includes S. pneumoniae conjugates, 1,5 and 7F saccharide capsules. 9. An immunogenic mixture of one of the claims 1-8, which also includes a conjugate of S. pneumoniae capsule saccharide 22F. 10. An immunogenic mixture of one of the claims in clauses 1-9, which also includes a conjugate of S. pneumoniae capsule saccharide 3 conjugates. 11. An immunogenic mixture of one of the claims in clauses 1-10 that also includes a S. pneumoniae capsule saccharide 6A conjugate. 12. An immunogenic mixture of one of the claims 1-11 where two different carrier proteins are conjugated separately for at least two serotypes of different S. pneumoniae capsule saccharides. 13. An immunogenic mixture of one of the claims in clauses 7-11 where three different carrier proteins are conjugated separately for at least three different serotypes of S. pneumoniae capsuler saccharides. 14. An immunogenic mixture of one of the claims in clauses 7-11 where four different carrier proteins are conjugated separately for at least four serotypes of different S. pneumoniae capsule saccharides. 15. An immunogenic mixture of one of the claims in clauses 7-11 where five different carrier proteins are conjugated separately for at least five different serotypes of S. pneumoniae capsuler saccharides. 16. An immunogenic mixture of claim 15 containing two or more carrier proteins selected from the following list: tetanus toxoid, dipteratoxoid, pneumolicin, protein D and PhtD or its protein synthesis. 17. An immunogenic mixture of one of the claims 1-16 consisting of S.pneumoniae capsule saccharide 1 conjugate with protein D. 18. An immunogenic mixture of any of the claims in clauses 1-17 comprising S. pneumoniae capsule saccharide 3 conjugate with protein D pneumolisin or PhtD or its fusion protein. 19. An immunogenic mixture of one of the claims 1-18 consisting of S. pneumoniae capsule saccharide 4 conjugate with protein D. 20. An immunogenic mixture of one of the claims 1-19 consisting of S.pneumoniae capsule saccharide 5 conjugate with protein D. 21. An immunogenic mixture of one of the claims 1-20 consisting of S.pneumoniae capsule saccharide 6B conjugated with protein D. 22. An immunogenic mixture of one of the claims 1-21 consisting of S.pneumoniae capsule saccharide 7F conjugated with protein D. 23. An immunogenic mixture of one of the claims 1-22 consisting of S.pneumoniae capsuler saccharide 9V conjugated with protein D. 24. An immunogenic mixture of one of the claims 1-23 consisting of S. pneumoniae capsule saccharide 14 conjugated with protein D. 25. An immunogenic mixture of one of the claims 1-24 consisting of S.pneumoniae capsule saccharide 23F conjugated with protein D. 26. An immunogenic mixture of one of the claims in clauses 1-25, consisting of S. pneumoniae capsules, 18C saccharide conjugate with tetanus toxoid. 27. An immunogenic mixture of one of the claims in clauses 1-26, consisting of S. pneumoniae capsule saccharide 19A conjugated with pneumolicin. 28. An immunogenic mixture of one of the claims 1-27 consisting of S. pneumoniae capsule saccharide 22F conjugated with PhtD or its fusion protein. 29. An immunogenic mixture of one of the claims 1-28 comprising S.pneumoniae capsuler saccharide 6A conjugate with neumolicin or H.influenzae protein, possibly selectively with protein D or PhtD or its fusion protein. 30. An immunogenic mixture according to one of the preceding claims, where 19A a capsule saccharide is directly conjugated to a carrier protein. 31. An immunogenic mixture of one of the claims in clauses 1-29, where 19A is a capsule saccharide conjugated with a carrier protein by a linker. 32. An immunogenic mixture of claim 31, where the linker is ADH. 33. An immunogenic mixture of claim 31 or 32, where the linker is chemically bound to the carrier protein by a carbodiemic chemistry, may use EDAC. 34. An immunogenic mixture of one of the claims in clauses 30-33, where 19A is conjugated with a carrier protein or linked chemically via CDAP. 35. An immunogenic mixture of any one of the claims in clauses 1-30 where the ratio of carrier protein to 19A saccharide is between 5:1 and 1:5, 4:1 and 1:1, or 3.5:1 and 2.5:1 (w/w). 36. An immunogenic mixture pursuant to one of the preceding claims, whereby a 19F capsule saccharide is directly conjugated to a carrier protein. 37. An immunogenic mixture pursuant to one of the claims of Claim 1-35, where the 19F capsule saccharide is conjugated with a linker carrier protein. 38. An immunogenic mixture of claim 37, where the linker is ADH. 39. An immunogenic mixture of claim 37 or 38, where the linker is chemically bound to the carrier protein by carbodiimide; EDAC may be chosen. 40. An immunogenic mixture of any one of the claims in Sections 36-39 where a 19F saccharide is conjugated with a carrier protein or linked chemically via CDAP. 41. An immunogenic mixture of any one of the claims in clauses 1-40 where the ratio of carrier protein to 19F saccharide is between 5:1 and 1:5, 4:1 and 1:1, or 2:1 and 1:1 (w/w). 42. An immunogenic mixture pursuant to one of the claims in Claim 1-41, incorporating a 22F capsule saccharide directly conjugated to a carrier protein. 43. An immunogenic mixture pursuant to one of the claims in Claim 1-41, comprising a 22F capsule saccharide conjugated with a linker carrier protein. 44. An immunogenic mixture pursuant to claim 43, where the linker is ADH. 45. An immunogenic mixture of claim 43 or 44, where the linker is chemically bound to the carrier protein by carbodiimide; EDAC may be chosen. 46. An immunogenic mixture of any one of the claims in Sections 42-45 where 22F saccharide is conjugated with a carrier protein or linked chemically via CDAP. 47. An immunogenic mixture of any one of the claims in clauses 1-46 where the ratio of carrier protein to 22F saccharide is between 5:1 and 1:5, 4:1 and 1:1, or 2:1 and 1:1 (w/w). 48. An immunogenic mixture pursuant to one of the prior claims, where the average size of 19A saccharide is greater than 100 kDa. 49. An immunogenic mixture of claim 48 where the average size of 19A saccharides is between 110 and 700 kDa, 110-300, 120-200, 130-180, or 140-160 kDa. 50. An immunogenic mixture of claim 48 or 49, where 19A saccharide is a naturally occurring polysaccharide or has been scaled by a factor no greater than x5. 51. An immunogenic mixture of any one of claims 48, 49, or 50, where 19A saccharide is scaled by microfluidization. 52. An immunogenic mixture of one of the preceding claims, where the given dose of 19A saccharide conjugate is between 1 and 10 Ug, 1 and 5 Ug, or 1 and 3 Ug of saccharide. 53. An immunogenic mixture of claim 52, where the given dose of 19A saccharide conjugate is 3 Ug of saccharide. 54. An immunogenic mixture according to one of the prior claims, consisting of 22F saccharide conjugates where the average size of the 22F saccharide is greater than 100 kDa. 55. Immunogenic mixtures of claim 54 where the average size of 22F saccharides is between 110 and 700 kDa, 110-300, 120-200, 130-180, or 150-170 kDa. 56. An immunogenic mixture of claim 54 or 55, where 22F saccharide is a naturally occurring polysaccharide or is scaled by a factor no greater than x5. 57. An immunogenic mixture of any one of claims 54, 55, or 56, where 22F saccharide is scaled by microfluidization. 58. An immunogenic mixture according to one of the prior claims, comprising 22F saccharide conjugates where the size of the 22F saccharide conjugate is between 1 and 10 Ug, 1 and 5 Ug, or 1 and 3 Ug of saccharides. 59. An immunogenic mixture of claim 58, where the given dose of 22F saccharide conjugate is 3 Ug of saccharide. 60. An immunogenic mixture according to one of the prior claims, where the average size of the saccharides is greater than 50 kDa. 61. An immunogenic mixture according to claim 60 consisting of serotype 1 with 25 saccharides averaging between 300 and 400 kDa. 62. An immunogenic mixture according to claim 60 or 61 consisting of serotype 4 with an average saccharide size between 75 and 125 kDa. 63. An immunogenic mixture pursuant to one of claims 60, 61, or 62, comprising serotype 5 with an average saccharide size between 350 and 450 kDa. 64. An immunogenic mixture pursuant to one of the claims in claims 60 through 63, consisting of serotype 6B with average saccharide sizes of 1000 and 1400 kDa. 65. An immunogenic mixture pursuant to one of the claims in claims 60 through 64, comprising serotype 7F with an average saccharide size between 200 and 300 kDa. 66. An immunogenic mixture pursuant to one of the claims in claims 60 through 65, comprising serotype 9V with an average saccharide size between 250 and 300 kDa. 67. An immunogenic mixture pursuant to one of the claims in claims 60 through 66, comprising serotype 24 with an average saccharide size between 200 and 250 kDa. 68. An immunogenic mixture pursuant to one of the claims in claims 60 through 67, comprising serotype 23F with an average saccharide size between 900 and 1000 kDa. 69. An immunogenic mixture of one of the preceding claims, comprising serotypes 5, 6B, and 23F (and possibly 6A) in their natural saccharide form. 70. An immunogenic mixture of one of the preceding claims, where the dose of the encapsulated saccharide conjugate is between 1 and 10 Ug, 1 and 5 Ug, or 1 and 3 Ug of saccharide per conjugate. 71. An immunogenic mixture of one of the preceding claims, comprising conjugates of serotypes 4, 18C, 19F, and 22F (and possibly 19A) at a given size of 3 Ug of saccharide per conjugate. 72. An immunogenic mixture of one of the preceding claims, comprising conjugates of serotypes 1, 5, 6B, 7F, 9V, 14, and 23F (and possibly 6A and/or 3) at a size of 1 Ug of saccharide per conjugate. 73. An immunogenic mixture of one of the preceding claims, comprising unconjugated S. pneumoniae saccharides of different serotypes from those conjugated such that the number of conjugated and unconjugated saccharide serotypes is less than or equal to 23. 74. An emunogenic mixture of any of the preceding claims, which also contains one or more conjugated and unconjugated proteins of S. pneumoniae. 75. An immunogenic mixture of claim 74 containing one or more unconjugated proteins of S. pneumoniae. 76. An immunogenic mixture of claim 74 or 75 where one or more proteins of S. pneumoniae are selected from the polyhistidine triad family (PhtX), the choline-binding protein family (CbpX), truncated CbpX, the LytX family, truncated LytX, truncated CbpX-LytX, chimeric proteins, detoxified pneumolic pneumolins (Ply), PspA, PsaA, Sp128, Sp101, Sp130, Sp125, and Sp133. 77. An immunogenic mixture pursuant to any one of claims 74, 75, or 76, which includes pneumolisin. 78. An immunogenic mixture of one of the claims in claims 74 through 77, which includes the protein PhtX. 79. An immunogenic mixture according to one of the prior claims, consisting of free pneumolisin or a carrier protein. 80. An immunogenic mixture as per one of the prior claims, comprising either free PhtX protein or a carrier protein. 81. An immunogenic mixture pursuant to claim 80, where the said PhtX protein is PhtD, PhtBD, or PhtDE fusion protein. 82. An immunogenic mixture as per one of the prior claims, which also includes an adjuvant. 83. An immunogenic mixture pursuant to claim 82, whereby the synergist is included with a liposome. 84. An immunogenic mixture according to claim 83, in which the synergistic agent is included (per dose of 0.5 mL) 0.1-10 mg phospholipids. 85. An immunogenic mixture according to claim 83 or 84, whereby the synergistic agent is included (per dose of 0.5 mL) 0.025-2.5 mg sterol. 86. An immunogenic mixture of one of the claims in Sections 83-85, in which the synergist is included (per dose of 0.5 mL) 5-60 Ug lipid derivative A. 87. An immunogenic mixture of one of the claims in Articles 83-86, in which the synergistic agent is included (per dose of 0.5 mL) 5-60 Ug saponin. 88. An immunogenic mixture of claim 82, whereby the synergist consists of an oil-in-water emulsion. 89. An immunogenic mixture of claim 88, whereby the synergistic agent is included (per dose of 0.5 mL) 0.5-15 mg metabolizable oil. 90. An immunogenic mixture of patent 88 or 89, whereby the synergistic agent is included (per dose of 0.5 mL) 0.1-10 mg emulsifier. 91. An immunogenic mixture of one of the claims in Articles 88-90, in which the synergistic agent is included (per dose of 0.5 mL) 0.5-20 mg tocopherol. 92. An immunogenic mixture of one of the claims in Sections 88-91, in which the synergist is included (per dose of 0.5 mL) 5-60 Ug lipid derivative A. 93. An immunogenic mixture of one of the claims in Sections 88-92, in which the synergistic agent is included (per dose of 0.5 mL) 0.025-2.5 mg sterol. 94. An immunogenic mixture of one of the claims in Sections 88-93, in which the synergistic agent is included (per dose of 0.5 mL) 5-60 Ug saponin. 95. An immunogenic mixture of claim 82, whereby the synergist consists of a metal salt and lipid derivative A. 96. An immunogenic mixture of claim 95, whereby the synergist(s) are included (per dose of 0.5 mL) 100-750, 200-500 or 300-400 Ug A1 in the form of aluminum phosphate. 97. An immunogenic mixture of claim 95 or 96, in which the synergistic agent is included (per dose of 0.5 mL) 5-60 Ug lipid derivative A. 98. An immunogenic mixture of any of the claims in Sections 1–97, containing at least or exactly 2,3,4,5,6,7,8,9,10,11, or 13 S. pneumoniae capsule saccharides conjugated to PhtD or its fusion protein. 99. An immunogenic mixture of any of the claims in Sections 1–97, containing at least or equal amounts of 2,3,4,5,6,7,8,9,10,11, or 13 S.pneumoniae capsule saccharides conjugated to neumolisin. 100. A complete vaccine kit containing the immunogenic mixture as per any one of the claims in Articles 1 through 97, and also containing for the concomitant or follow-up administration of an adjuvant as specified in any one of the claims in Articles 83 through 99. 101. A vaccine consisting of an immunogenic mixture as per one of the claims in Articles 1 through 99 and a pharmaceutically acceptable filler. 102. The procedure for manufacturing the vaccine under claim 101, which includes the steps for combining the immunogenic mixture of any one of claims 1 through 99 with a pharmaceutically acceptable filler. 103. Methods of immunosuppressing a human host against disease caused by Streptococcus pneumoniae infection, which include administering a dose to the host that provides immunoprotection of one of the immunogenic mixtures of Rights 1 through 99 or the vaccine of Rights 101. 104. Method of claim 103 where the homeowner is an elderly person and the illness is one or both of pneumonia or invasive pneumococcal disease (IPD). 105. Method of claim 103 or 104 where the homeowner is an elderly person and the illness is a severe form of chronic obstructive pulmonary disease (COPD). 106. Method of claim 103 where the person homeowner is an infant and the disease is otitis media. 107. Method of claim 103 or 106 where the homeowner is an infant and the disease is meningitis and/or sepsis. 108. In the manner of either claim 103, 106 or 107, where the homeowner is an infant and the illness is pneumonia and/or conjunctivitis. 109. An immunogenic mixture of any one of the claims in Articles 1 through 99 or a vaccine of claim 101 for use in the treatment or prevention of disease caused by infection with Streptococcus pneumoniae. 110. The use of immunogenic mixtures or vaccines under any of the claims in Articles 1 through 99, or vaccines under claim 101, in the manufacture of drugs for the treatment or prevention of diseases caused by Streptococcus pneumoniae infection. 111. Use of Claim 110 where the disease is one or both of pneumonia or invasive pneumococcal disease (IPD) in the elderly. 112. Use of claim 110 or 111 where the disease is a severe form of chronic obstructive pulmonary disease (COPD) in the elderly. 113. Use of claim 110 where the disease is infantile otitis media. 114. Use of claim 110 or 113 where the disease is meningitis and/or bacterial blood infection in an infant. 115. The use of any one of the claims 110, 113, or 114 where the disease is pneumonia and/or conjunctivitis in an infant. 116. Methods of providing a protective immune response in infants to otitis media, which include the administration of, separately or in combination with, the following components: (i) an immunogenic mixture or a vaccine under any of the claims in Articles 1 through 99; and (ii) Haemophilus influenzae D protein, which may be free and/or conjugated. 117. Methods of providing a protective immune response in infants against S. pneumoniae by administering an immunogenic mixture or a vaccine of one of the prior claims. 118. Methods of providing a protective immune response in the elderly against S. pneumoniae by administering, sequentially or concurrently (i) an immunogenic mixture or vaccine of any prior claim; (ii) one or more S. pneumoniae surface proteins selected from a group containing the PhtX and pneumolic families. 119. An immunogenic mixture of any one of the claims 1–99 or a vaccine of claim 101, incorporating saccharide conjugates derived from at least all of the following serotypes: 4, 6B, 9V, 14, 18C, 19F, 23F, 1, 5, 7F, where GMC antibody titers induced against one or more vaccine components of 4, 6B, 9V, 14, 18C, 19F, and 23F are not significantly inferior to those induced by Prevnar R vaccine in people who have received the vaccine. 120. An immunogenic mixture of claim 119 in which GMC antibody titers induced against serotype 4 are not significantly inferior to those induced by Prevnar R vaccine in vaccinated individuals. 121. Immunogenic mixtures of claims 119 or 120 where GMC antibody titers induced against serotype 6B are not significantly inferior to those induced by Prevnar R vaccine in vaccinated individuals. 122. An immunogenic mixture of one of the claims in clauses 119-121 where GMC antibody titers induced against serotype 9V are not significantly inferior to those induced by the Prevnar R vaccine in vaccinated individuals. 123. An immunogenic mixture of one of the claims in clauses 119-122 where GMC antibody titers induced against serotype 14 are not significantly inferior to those induced by the Prevnar R vaccine in vaccinated individuals. 124. An immunogenic mixture of one of the claims in clauses 119-123 where GMC antibody titers induced against serotype 18C are not significantly inferior to those induced by the Prevnar R vaccine in vaccinated individuals. 125. An immunogenic mixture of one of the claims in clauses 119-124 in which GMC antibody titers induced against serotype 19F are not significantly inferior to those induced by the Prevnar R vaccine in vaccinated individuals. 126. An immunogenic mixture of one of the claims in clauses 119-125 where GMC antibody titers induced against serotype 23F are not significantly inferior to those induced by the Prevnar R vaccine in vaccinated individuals. 127. An immunogenic mixture of any one of the claims in Articles 119–126, comprising a serotype 3 saccharide conjugate. 128. An immunogenic mixture of any one of the claims in Articles 119–127, comprising a serotype 6A saccharide conjugate. 129. An immunogenic mixture of any one of the claims in Articles 119–128, comprising serotype 19A saccharide conjugate. 130. An immunogenic mixture of one of the claims in Sections 119–129 comprising a serotype 22F saccharide conjugate. 131. An immunogenic mixture of any of the claims in Articles 119–130, incorporating a crystalline bulking agent, may include mannitol. 132. An immunogenic mixture of claim 131, comprising a sugar, possibly sucrose. 133. An immunogenic mixture comprising at least four S.pneumoniae capsules, saccharide conjugates containing saccharides from different serotypes of S.pneumoniae, where at least one saccharide is conjugated to PhtD or its fusion protein, and the immunogenic mixture is capable of eliciting an immune response to PhtD.