Claims
- 1. A modified group B polysaccharide of Neisseria meningitides wherein the sialic acid residue N-acetyl groups of the native polysaccharide are replaced by C.sub.4 -C.sub.8 acyl groups to an extent that when said modified group B polysaccharide is conjugated to protein the amount of substitution of acyl for acetyl groups is sufficient to reduce the inducement of antibodies which bind native GBMP, compared to the binding of native GBMP to antibodies induced by a N-Pr-GBMP-protein conjugate.
- 2. A modified group B polysaccharide of E. coli K1 capsular polysaccharide wherein the sialic acid residue N-acetyl groups of the native polysaccharide are replaced by C.sub.4 -C.sub.8 acyl groups to an extent that when said modified group B polysaccharide is conjugated to protein the amount of substitution of acyl for acetyl groups is sufficient to reduce the inducement of antibodies which bind native GBMP, compared to the binding of native GBMP to antibodies induced by a N-Pr-GBMP-protein conjugate.
- 3. The modified polysaccharide according to claim 1, wherein the C.sub.4 -C.sub.8 acyl group is selected from the group consisting of n-butanoyl, isbutanoyl, n-pentanoyl, n-hexyanol, n-heptanoyl and n-octanoyl.
- 4. The modified polysaccharide according to claim 3, wherein the C.sub.4 -C.sub.8 acyl group is selected from the group consisting of n-butanoyl, isbutanoyl, n-pentanoyl and n-hexyanoyl.
- 5. The modified polysaccharide according to claim 2, wherein the C.sub.4 -C.sub.8 acyl group is selected from the group consisting of n-butanoyl, isbutanoyl, n-pentanoyl, n-hexyanol, n-heptanoyl and n-octanoyl.
- 6. The modified polysaccharide according to claim 5, wherein the C.sub.4 -C.sub.8 acyl group is selected from the group consisting of n-butanoyl, isbutanoyl, n-pentanoyl and n-hexyanoyl.
- 7. The modified polysaccharide according to claim 1 having an average molecular weight within the range of 10,000 to 50,000 Daltons.
- 8. The modified polysaccharide according to claim 2 having an average molecular weight within the range of 10,000 to 50,000 Daltons.
- 9. The polysaccharide according to claim 1 wherein about 90% to 100% of the N-deacetylated have been replaced by C.sub.4 -C.sub.8 acyl groups.
- 10. The polysaccharide according to claim 2 wherein about 90% to 100% of the N-deacetylated have been replaced by C.sub.4 -C.sub.8 acyl groups.
- 11. The modified polysaccharide according to claim 1 wherein about 90% to 100% of the sialic acid residue N-acetyl groups are replaced by C.sub.4 -C.sub.8 acyl groups.
- 12. The polysaccharide according to claim 2 wherein about 90% to 100% of the sialic acid residue N-acetyl groups are replaced by C.sub.4 -C.sub.8 acyl groups.
- 13. The modified group B polysaccharide according to claim 1 wherein about 30% to 100% of the N-acetyl groups have been N-deacetylated.
- 14. The modified group B polysaccharide according to claim 2 wherein about 30% to 100% of the N-acetyl groups have been N-deacetylated.
- 15. The modified group B polysaccharide according to claim 1 wherein the N-acetyl group is replaced by an n-butanoyl group.
- 16. The modified group B polysaccharide according to claim 2 wherein the N-acetyl group is replaced by an n-butanoyl group.
- 17. An antigenic conjugate comprising the modified group B polysaccharide according to claim 1 or claim 2 conjugated to an immunogenically suitable protein.
- 18. The conjugate according to claim 17, wherein the C.sub.4 -C.sub.8 acyl group is selected from the group consisting of n-butanoyl, isbutanoyl, n-pentanoyl, n-hexyanol, n-heptanoyl and n-octanoyl.
- 19. The conjugate according to claim 18, wherein the C.sub.4 -C.sub.8 acyl group is selected from the group consisting of n-butanoyl, isbutanoyl, n-pentanoyl and n-hexyanoyl.
- 20. The conjugate according to claim 19, wherein the C.sub.4 -C.sub.8 acyl group is of n-butanoyl.
- 21. The conjugate according to claim 17 wherein the protein elicits antibodies to bacteria.
- 22. The conjugate according to claim 17 wherein the protein is selected from the group consisting of tetanus toxoid, diphtheria toxoid, cross-reacting material (CRM) and a meningococcal outer membrane protein.
- 23. The conjugate according to claim 17 wherein the protein and the polysaccharide are covalently linked through a --CH.sub.2 --NH-- linkage and wherein the N of the linkage is contributed by the protein.
- 24. The conjugate according to claim 23 wherein the C.sub.4 -C.sub.8 acyl group is of n-butanoyl.
- 25. The conjugate according to claim 22, wherein the CRM is CRM.sub.197.
- 26. A pharmaceutical composition comprising a conjugate according to claim 17 and a pharmaceutically acceptable carrier.
- 27. The pharmaceutical composition according to claim 26, further comprising a physiologically acceptable adjuvant.
- 28. The pharmaceutical composition according to claim 27, wherein said adjuvant is selected from the group consisting of aluminum hydroxide, aluminum phosphate and aluminum sulphate.
- 29. A method of eliciting an antibody response in mammals against N. meningitidis and E. coli K1 bacteria, said method comprising the step of administering parenterally to the mammals subject to infection by said bacteria an amount of a pharmaceutical composition according to claim 26 which is sufficient to elicit said antibody response.
- 30. The method according to claim 29, wherein the pharmaceutical composition is administered in a dosage amount of about 1 to 25 micrograms per kilogram body weight.
- 31. A method of preparing the modified polysaccharide according to either claim 1 or 2 comprising replacing N-acetyl groups of the native polysaccharide with C.sub.4 -C.sub.8 acyl groups.
- 32. A method of preparing the modified polysaccharide according to claim 31 wherein the C.sub.4 -C.sub.8 acyl groups are selected from the group consisting of n-butanoyl, isbutanoyl, n-pentanoyl, n-hexyanol, n-heptanoyl and n-octanoyl.
- 33. A method of preparing the modified polysaccharide according to claim 32 wherein the C.sub.4 -C.sub.8 acyl groups are n-butanoyl.
- 34. A method of preparing a polysaccharide-protein conjugate comprising covalently binding the modified polysaccharide according to either of claims 1 or 2 to an immunologically suitable protein.
- 35. The method of preparing the polysaccharide-protein conjugate according to claim 34 wherein the C.sub.4 -C.sub.8 acyl groups are selected from the group consisting of n-butanoyl, isbutanoyl, n-pentanoyl, n-hexyanol, n-heptanoyl and n-octanoyl.
- 36. The method of preparing the modified polysaccharide-protein conjugate according to claim 35 wherein the C.sub.4 -C.sub.8 acyl groups are n-butanoyl.
- 37. The method according to claim 34 wherein the protein elicits antibodies to bacteria.
- 38. The method according to claim 37 wherein the protein is selected from the group consisting of tetanus toxoid, diphtheria toxoid, cross-reacting material (CRM) and a meningococcal outer membrane protein.
Parent Case Info
This is a continuation of application Ser. No. 07/956,830, filed on Oct. 5, 1992 now abandoned, which is a continuation of application Ser. No. 07/448,195, filed on Dec. 14, 1989, now abandoned.
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Foreign Referenced Citations (1)
Number |
Date |
Country |
00098581A3 |
Jan 1984 |
EPX |
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Continuations (2)
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Number |
Date |
Country |
Parent |
956830 |
Oct 1992 |
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Parent |
448195 |
Dec 1989 |
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