Capsular polysaccharide solubilisation and combination vaccines
Precipitated bacterial capsular polysaccharides can be efficiently re-solubilized using alcohols as solvents. The invention provides a process for purifying a bacterial capsular polysaccharide, comprising the steps of (a) precipitation of said polysaccharide, followed by (b) solubilization of the precipitated polysaccharide using ethanol. CTAB can be used for step (a). The material obtained, preferably following hydrolysis and sizing, can be conjugated to a carrier protein and formulated as a vaccine. Also, in vaccines comprising saccharides from the serogroups A and C, the invention provides that the ratio (w/w) of MenA saccharide:MenC saccharide is >1.
1. A kit comprising: (a) capsular saccharide from N. meningitidis serogroup A, in lyophilized form; and (b) capsular saccharides from N. meningitidis serogroups C, W135 and Y, in liquid form wherein the ratio (w/w) of serogroup A saccharide to serogroup C saccharides is greater than 1.
2. The kit of claim 1 , wherein one or more of the saccharides is conjugated to a carrier protein.
3. The kit of claim 1 , wherein one or more of the saccharides is an oligosaccharide.
4. The kit of claim 1 , wherein one or more of the saccharides is adsorbed to an aluminium hydroxide adjuvant.
5. The kit of claim 1 , wherein component (b) comprises an aluminium salt adjuvant.
6. The kit of claim 5 , wherein component (b) comprises an aluminium phosphate adjuvant.
7. The kit of claim 1 , wherein the capsular saccharide from N. meningitidis serogroup A is conjugated to a bacterial toxin or toxoid.
8. The kit of claim 7 , wherein the bacterial toxin or toxoid is diphtheria toxoid, tetanus toxoid or the CRM 197 diphtheria toxoid.
9. The kit of claim 2 , wherein the conjugated capsular saccharide from N. meningitidis serogroup A has a saccharide:protein ratio (w/w) of between 0.5:1 and 5:1.
10. The kit of claim 3 , wherein the capsular saccharide from N. meningitidis serogroup A has a saccharide:protein ratio (w/w) of between 0.5:1 and 5:1.
11. The kit of claim 7 , wherein the conjugated capsular saccharide from N. meningitidis serogroup A has a saccharide:protein ratio (w/w) of between 0.5:1 and 5:1.
12. The kit of claim 1 , wherein the serogroup A saccharide has an average degree of polymerization of between 10 and 20.
13. The kit of claim 2 , wherein the serogroup A saccharide has an average degree of polymerization of between 10 and 20.
14. The kit of claim 3 , wherein the serogroup A saccharide has an average degree of polymerization of between 10 and 20.
15. The kit of claim 1 , wherein the serogroup W135 saccharide has an average degree of polymerization of between 15 and 25.
16. The kit of claim 2 , wherein the saccharide from serogroup W135 is conjugated to the carrier protein.
17. The kit of claim 16 , wherein the serogroup W135 saccharide has an average degree of polymerization of between 15 and 25.
18. The kit of claim 3 , wherein the serogroup W135 saccharide has an average degree of polymerization of between 15 and 25.
19. The kit of claim 1 , wherein the serogroup Y saccharide has an average degree of polymerization of between 15 and 25.
20. The kit of claim 2 , wherein the saccharide from serogroup Y is conjugated to the carrier protein.
21. The kit of claim 20 , wherein the serogroup Y saccharide has an average degree of polymerization of between 15 and 25.
22. The kit of claim 3 , wherein the serogroup Y saccharide has an average degree of polymerization of between 15 and 25.
23. The kit of claim 1 , wherein the serogroup C saccharide has from 12 to 22 repeating units.
24. The kit of claim 1 , wherein the ratio (w/w) of saccharides from serogroup A to each of the saccharides of (b) is 2:1.
25. The kit of claim 19 , wherein the saccharide from serogroup C is conjugated to the carrier protein.
26. The kit of claim 25 , wherein the serogroup C saccharide has from 12 to 22 repeating units.
27. The kit of claim 25 , wherein the ratio (w/w) of saccharides from serogroup A to each of the saccharides of (b) is 2:1.
28. The kit of claim 3 , wherein the serogroup C saccharide has from 12 to 22 repeating units.
29. The kit of claim 3 , wherein the ratio (w/w) of saccharides from serogroup A to each of the saccharides of (b) is 2:1.
30. The kit of claim 1 , wherein the saccharides are unconjugated.