Claims
- 1. A multivalent conjugate molecule comprising a carrier protein with at least three different bacterial capsular polysaccharides covalently linked to the carrier protein, wherein the molecule elicits protective antibodies.
- 2. The conjugate molecule of claim 1 comprising four different bacterial capsular polysaccharides covalently linked to the carrier protein.
- 3. The conjugate molecule of claim 1 comprising five different bacterial capsular polysaccharides covalently linked to the carrier protein.
- 4. The conjugate molecule of claim 1 comprising six different bacterial capsular polysaccharides covalently linked to the carrier protein.
- 5. The conjugate molecule of claim 1, wherein the carrier protein is selected from the group consisting of Cα, Cβ, tetanus toxoid, diphtheria toxoid, diphtheria toxoid analog CRM197, and a porin protein.
- 6. The conjugate molecule of claim 1, wherein the bacterial capsular polysaccharides are different Group B Streptococcus capsular polysaccharides selected from the group consisting of type Ia, type Ib, type II, type III, type V, and type VIII.
- 7. The conjugate molecule of claim 6, wherein the Group B Streptococcus capsular polysaccharides are type Ia, type III and type V.
- 8. The conjugate molecule of claim 7, wherein the carrier protein is Cβ.
- 9. The conjugate molecule of claim 6, wherein the bacterial capsular polysaccharides are of a size of between 80 and 120 kilodaltons.
- 10. The conjugate molecule of claim 6, wherein between about 5 and 20% of the sialic acid residues of the bacterial capsular polysaccharides are covalently linked to the carrier protein.
- 11. The conjugate molecule of claim 6, wherein the bacterial capsular polysaccharides are present in equimolar amounts.
- 12. The conjugate molecule of claim 1, wherein the bacterial capsular polysaccharides are Neisseria meningitidis capsular polysaccharides selected from the group consisting of A, B, C, W, and Y.
- 13. The conjugate molecule of claim 12, wherein the Neisseria meningitidis capsular polysaccharides are B, C, and Y.
- 14. The conjugate c molecule of claim 12, wherein the Neisseria meningitidis capsular polysaccharides are C, Y, and W-135.
- 15. The conjugate molecule of claim 12, wherein the carrier protein is a porin protein, tetanus toxoid, or CRM197.
- 16. The conjugate molecule of claim 14, wherein the carrier protein is tetanus toxoid.
- 17. A method of preparing a multivalent conjugate molecule, the method comprising covalently linking at least three different bacterial capsular polysaccharides to a carrier protein.
- 18. The method of claim 17, wherein covalently linking the bacterial capsular polysaccharides to the carrier protein comprises steps of:
(a) oxidizing the polysaccharides; (b) coupling the oxidized polysaccharides to the carrier protein.
- 19. The method of claim 18, wherein the polysaccharides are coupled to the carrier protein by reductive animation.
- 20. The method of claim 18, wherein the polysaccharides are conjugated to the carrier protein by a bispacer coupling with a linker.
- 21. The method of claim 17, wherein the carrier protein is selected from the group consisting of Cα, Cβ, tetanus toxoid, diphtheria toxoid, diphtheria toxoid analog CRM197, and a porin protein.
- 22. The method of claim 17, wherein the bacterial capsular polysaccharides are different Group B Streptococcus capsular polysaccharides selected from the group consisting of type Ia, type Ib, type II, type III, type V, and type V.
- 23. The method of claim 22, wherein the Group B Streptococcus capsular polysaccharides are type Ia, type III, and type V.
- 24. The method of claim 23, wherein the carrier protein Cp.
- 25. The method according to claim 22, wherein between about 5 and 20% of the sialic acid residues of the bacterial capsular polysaccharides are oxidized.
- 26. The method according to claim 22, wherein between about 5 and 20% of the sialic acid residues of the bacterial capsular polysaccharides are coupled to protein.
- 27. The method of claim 17, wherein the bacterial capsular polysaccharides are Neisseria meningitidis capsular polysaccharide selected from the group consisting of A, B, C, W, and Y.
- 28. The method of claim 27, wherein the Neisseria meningitidis capsular polysaccharides are B, C, and Y.
- 29. The method of claim 27, wherein the Neisseria meningitidis capsular polysaccharides are C, Y, and W-135.
- 30. The method of claim 27, wherein the carrier protein is recombinant porin B, tetanus toxoid, or CRM197.
- 31. The method of claim 29, wherein the carrier protein is tetanus toxoid.
- 32. A method of preventing or attenuating an infection in a mammal, the method comprising administering to the mammal a multivalent conjugate molecule comprising a carrier protein with at least three different bacterial capsular polysaccharides covalently linked to the carrier protein, wherein the multivalent conjugate molecule is administered in an amount sufficient to elicit protective antibodies against the bacterial capsular polysaccharides.
- 33. The method of claim 32, wherein the carrier protein is selected from the group consisting of Cα, Cβ, tetanus toxoid, diphtheria toxoid, diphtheria toxoid analog CRM197, and a porin protein.
- 34. The method of claim 32, wherein the multivalent conjugate molecule is administered to prevent or attenuate an infection caused by Group B Streptococcus and the bacterial capsular polysaccharides of the conjugate molecule are different Group B Streptococcus capsular polysaccharides selected from the group consisting of type Ia, type Ib, type II, type III, type V, and type VIII.
- 35. The method of claim 34, wherein the Group B Streptococcus polysaccharides are type Ia, type III and type V.
- 36. The method of claim 35, wherein the carrier protein is Cβ.
- 37. The method of claim 32, wherein the multivalent conjugate molecule is administered to prevent or attenuate an infection caused by Neisseria meningitidis and the bacterial capsular polysaccharides of the conjugate molecule are different Neisseria meningitidis capsular polysaccharides selected from the group consisting of A, B, C, W, and Y.
- 38. The method of claim 37, wherein the Neisseria meningitidis capsular polysaccharides are B, C, and Y.
- 39. The method of claim 37, wherein the Neisseria meningitidis capsular polysaccharides are C, Y, and W-135.
- 40. The method of claim 37, wherein the carrier protein is recombinant porin B, tetanus toxoid, or CRM197.
- 41. The method of claim 39, wherein the carrier protein is tetanus toxoid.
- 42. A pharmaceutical composition comprising a multivalent conjugate molecule comprising a carrier protein with at least three different bacterial capsular polysaccharides covalently linked to the carrier protein and a pharmacological acceptable carrier, wherein the multivalent conjugate molecule is in an amount sufficient to elicit protective antibodies against the three different bacterial capsular polysaccharides.
- 43. The pharmaceutical composition of claim 42, wherein the carrier protein is selected from the group consisting of Cα, Cβ, tetanus toxoid, diphtheria toxoid, CRM197, and a porin protein.
- 44. The pharmaceutical composition of claim 42, wherein the bacterial capsular polysaccharides are different Group B Streptococcus capsular polysaccharides selected from the group consisting of type Ia, type Ib, type II, type III, type V, and type VIII.
- 45. The pharmaceutical composition of claim 44, wherein the Group B Streptococcus capsular polysaccharides are type Ia, type III and type V.
- 46. The pharmaceutical composition of claim 45, wherein the carrier protein is Cβ.
- 47. The pharmaceutical composition of claim 42, wherein the bacterial capsular polysaccharides of the immunogenic molecule are different Neisseria meningitidis capsular polysaccharides selected from the group consisting of A, B, C, W, and Y.
- 48. The pharmaceutical composition of claim 47, wherein the Neisseria meningitidis capsular polysaccharides are B, C, and Y.
- 49. The pharmaceutical composition of claim 47, wherein the Neisseria meningitidis capsular polysaccharides are C, Y, and W-135.
- 50. The pharmaceutical composition of claim 47, wherein the carrier protein is tetanus toxoid, recombinant porin B or CRM197.
- 51. The pharmaceutical composition of claim 49, wherein the carrier protein is tetanus toxoid.
CROSS-REFERENCES TO RELATED APPLICATIONS
[0001] This application claims benefit of priority to U.S. provisional application No. 60/399,949, filed Jul. 30, 2002, which application is herein incorporated by reference.
Provisional Applications (1)
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Number |
Date |
Country |
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60399949 |
Jul 2002 |
US |