Formulations which stabilize and inhibit precipitation of immunogenic compositions

1. A formulation which stabilizes a polysaccharide-protein conjugate, the formulation comprising

(i) a pH buffered saline solution, wherein the buffer has a pKa of about 3.5 to about 7.5,

(ii) polysorbate 80 at a final concentration of at least 0.001% to 0.05% polysorbate 80 weight/volume of the formulation, and

(iii) one or more polysaccharide-protein conjugates comprising one or more pneumococcal polysaccharides.

2. The formulation of claim 1 , wherein the polysaccharide-protein conjugate formulation is comprised in a container means selected from one or more of the group consisting of a vial, a vial stopper, a vial closure, a glass closure, a rubber closure, a plastic closure, a syringe, a syringe stopper, a syringe plunger, a flask, a beaker, a graduated cylinder, a fermentor, a bioreactor, tubing, a pipe, a bag, a jar, an ampoule, a cartridge and a disposable pen.

3. The formulation of claim 2 , wherein the container means is siliconized.

4. The formulation of claim 1 , wherein the buffer is succinate at a final concentration of 1 mM to 10 mM.

5. The formulation of claim 1 , wherein the polysorbate 80 has a final concentration of at least 0.01% to 0.05% polysorbate 80 weight/volume of the formulation.

6. The formulation of claim 1 , further comprising one or more meningococcal polysaccharides, one or more meningococcal antigenic proteins, or a combination thereof.

7. The formulation of claim 1 , further comprising one or more streptococcal polysaccharides, one or more streptococcal antigenic proteins, or a combination thereof.

8. The formulation of claim 1 , wherein the polysaccharide-protein conjugate formulation is a 7-valent pneumococcal conjugate (7vPnC) formulation comprising a S. pneumoniae serotype 4 polysaccharide conjugated to a CRM 197 polypeptide, a S. pneumoniae serotype 6B polysaccharide conjugated to a CRM 197 polypeptide, a S. pneumoniae serotype 9V polysaccharide conjugated to a CRM 197 polypeptide, a S. pneumoniae serotype 14 polysaccharide conjugated to a CRM 197 polypeptide, a S. pneumoniae serotype 18C polysaccharide conjugated to a CRM 197 polypeptide, a S. pneumoniae serotype 19F polysaccharide conjugated to a CRM 197 , polypeptide and a S. pneumoniae serotype 23F polysaccharide conjugated to a CRM 197 polypeptide.

9. The formulation of claim 1 , wherein the polysaccharide-protein conjugate formulation is a 13-valent pneumococcal conjugate (13vPnC) formulation comprising a S. pneumoniae serotype 4 polysaccharide conjugated to a CRM 197 polypeptide, a S. pneumoniae serotype 6B polysaccharide conjugated to a CRM 197 polypeptide, a S. pneumoniae serotype 9V polysaccharide conjugated to a CRM 197 polypeptide, a S. pneumoniae serotype 14 polysaccharide conjugated to a CRM 197 polypeptide, a S. pneumoniae serotype 18C polysaccharide conjugated to a CRM 197 polypeptide, a S. pneumoniae serotype 19F polysaccharide conjugated to a CRM 197 polypeptide, a S. pneumoniae serotype 23F polysaccharide conjugated to a CRM 197 polypeptide, a S. pneumoniae serotype 1 polysaccharide conjugated to a CRM 197 polypeptide, a S. pneumoniae serotype 3 polysaccharide conjugated to a CRM 197 polypeptide, a S. pneumoniae serotype 5 polysaccharide conjugated to a CRM 197 polypeptide, a S. pneumoniae serotype 6A polysaccharide conjugated to a CRM 197 polypeptide, a S. pneumoniae serotype 7F polysaccharide conjugated to a CRM 197 polypeptide and a S. pneumoniae serotype 19A polysaccharide conjugated to a CRM 197 polypeptide.

10. The formulation of claim 1 , wherein the formulation further comprises an adjuvant.

11. The formulation of claim 10 , wherein the adjuvant is aluminum phosphate.

12. The formulation of claim 9 , wherein the formulation further comprises an adjuvant.

13. The formulation of claim 12 , wherein the adjuvant is aluminum phosphate.

14. The formulation of claim 13 wherein the aluminum phosphate is present at a final concentration of about 0.25 mg/mL.

15. The formulation of claim 9 , wherein the buffer is succinate at a final concentration of 1 mM to 10 mM and pH 5.8 to 6.0.

16. The formulation of claim 1 , wherein the buffer is phosphate, succinate, histidine or citrate.

17. The formulation of claim 3 , wherein the succinate buffer has a ph of 5.8 to 6.0.

18. The formulation of claim 1 , wherein the pH buffered saline solution contains sodium chloride.

19. The formulation of claim 15 , wherein the buffer is succinate at a final concentration of 5 mM.

20. The formulation of claim 19 , wherein the buffer is at pH 5.8.

21. A formulation which stabilizes a polysaccharide-protein conjugate, the formulation comprising

(i) a pH buffered saline solution, wherein the buffer is succinate at a final concentration of about 1 mM to 10 mM and pH 5.8 to 6.0;

(ii) polysorbate 80 at a final concentration of at least 0.01% to 0.05% polysorbate 80 weight/volume of the formulation;

(iii) a 13-valent pneumococcal conjugate (13vPnC) formulation comprising a S. pneumoniae serotype 4 polysaccharide conjugated to a CRM 197 polypeptide, a S. pneumoniae serotype 6B polysaccharide conjugated to a CRM 197 polypeptide, a S. pneumoniae serotype 9V polysaccharide conjugated to a CRM 197 polypeptide, a S. pneumoniae serotype 14 polysaccharide conjugated to a CRM 197 polypeptide, a S. pneumoniae serotype 18C polysaccharide conjugated to a CRM 197 polypeptide, a S. pneumoniae serotype 19F polysaccharide conjugated to a CRM 197 polypeptide, a S. pneumoniae serotype 23F polysaccharide conjugated to a CRM 197 polypeptide, a S. pneumoniae serotype 1 polysaccharide conjugated to a CRM 197 polypeptide, a S. pneumoniae serotype 3 polysaccharide conjugated to a CRM 197 polypeptide, a S. pneumoniae serotype 5 polysaccharide conjugated to a CRM 197 polypeptide, a S. pneumoniae serotype 6A polysaccharide conjugated to a CRM 197 polypeptide, a S. pneumoniae serotype 7F polysaccharide conjugated to a CRM 197 polypeptide and a S. pneumoniae serotype 19A polysaccharide conjugated to a CRM 197 polypeptide.

22. The formulation of claim 21 , wherein the final concentration of the succinate buffer is 5 mM.

23. The formulation of claim 21 , wherein the pH buffered saline solution contains sodium chloride,

24. The formulation of claim 23 , wherein the sodium chloride is present at a final concentration of 150 mM.

25. The formulation of claim 21 , wherein the formulation further comprises an adjuvant, the adjuvant being aluminum phosphate.

26. A formulation which stabilizes a polysaccharide-protein conjugate, the formulation comprising

(i) a pH buffered saline solution containing sodium chloride, wherein the buffer is succinate at a final concentration of about 5 mM and ph 5.8;

(ii) polysorbate 80 at a final concentration of at least 0.01% to 0.05% polysorbate 80 weight/volume of the formulation;

(iii) a 13-valent pneumococcal conjugate (13vPnC) formulation comprising a S. pneumoniae serotype 4 polysaccharide conjugated to a CRM 197 polypeptide, a S. pneumoniae serotype 6B polysaccharide conjugated to a CRM 197 polypeptide, a S. pneumoniae serotype 9V polysaccharide conjugated to a CRM 197 polypeptide, a S. pneumoniae serotype 14 polysaccharide conjugated to a CRM 197 polypeptide, a S. pneumoniae serotype 18C polysaccharide conjugated to a CRM 197 polypeptide, a S. pneumoniae serotype 19F polysaccharide conjugated to a CRM 197 polypeptide, a S. pneumoniae serotype 23F polysaccharide conjugated to a CRM 197 polypeptide, a S. pneumoniae serotype 1 polysaccharide conjugated to a CRM 197 polypeptide, a S. pneumoniae serotype 3 polysaccharide conjugated to a CRM 197 polypeptide, a S. pneumoniae serotype 5 polysaccharide conjugated to a CRM 197 polypeptide, a S. pneumoniae serotype 6A polysaccharide conjugated to a CRM 197 polypeptide, a S. pneumoniae serotype 7F polysaccharide conjugated to a CRM 197 polypeptide and a S. pneumoniae serotype 19A polysaccharide conjugated to a CRM 197 polypeptide; and

(iv) an adjuvant comprising aluminum phosphate present at a final concentration of about 0.25 mg/mL.