Immunogenic compositions and uses thereof
The invention relates to immunogenic compositions comprising a capsular polysaccharide (CP) from Streptococcus agalactiae , commonly referred to as group B streptococcus (GBS), conjugated to a carrier protein, and optionally including an aluminum-based adjuvant. The invention further relates to methods for inducing an immune response in subjects against GBS and/or for reducing or preventing invasive GBS disease in subjects using the compositions disclosed herein. The resulting antibodies can be used to treat or prevent GBS infection via passive immunotherapy.
1. An immunogenic composition comprising polysaccharide-protein conjugates, wherein
(i) each of the conjugates comprise a capsular polysaccharide from a different serotype of group B Streptococcus (GBS) conjugated to CRM 197 , wherein the serotypes comprise serotypes Ia, Ib, II, III, IV, and V, wherein each capsular polysaccharide has a sialic acid level of greater than 60 percent, and
(ii) the immunogenic composition further comprises one or more of a pharmaceutically acceptable excipient, buffer, stabilizer, adjuvant, a cryoprotectant, a salt, a divalent cation, a non-ionic detergent, an inhibitor of free radical oxidation, a carrier, or a mixture thereof; and
wherein the immunogenic composition comprises a total conjugate dose of 60 mcg/mL to 360 mcg/mL.
2. The immunogenic composition of claim 1 , wherein the immunogenic composition comprises a total conjugate dose of 60 mcg/mL to 240 mcg/mL.
3. The immunogenic composition of claim 1 , wherein the immunogenic composition comprises a total conjugate dose of 60 mcg/mL to 120 mcg/mL.
4. The immunogenic composition of claim 1 , wherein the immunogenic composition comprises a total conjugate dose of 120 mcg/mL to 240 mcg/mL.
5. The immunogenic composition of claim 1 , wherein the immunogenic composition comprises a total conjugate dose of 240 mcg/mL.
6. The immunogenic composition of claim 1 , wherein the buffer is selected from the group consisting of HEPES, PIPES, MES, Tris (trimethamine), phosphate, acetate, borate, citrate, glycine, histidine and succinate.
7. The immunogenic composition of claim 1 , wherein the excipient is selected from the group consisting of starch, glucose, lactose, sucrose, trehalose, raffinose, stachyose, melezitose, dextran, mannitol, lactitol, palatinit, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, glycine, arginine, lysine, sodium chloride (NaCl), dried skim milk, glycerol, propylene glycol, water, and ethanol.
8. The immunogenic composition of claim 1 , further comprising a surfactant is-selected from the group consisting of polyoxyethylene sorbitan fatty acid esters, polysorbate-80, polysorbate-60, polysorbate-40, polysorbate-20, and polyoxyethylene alkyl ethers.
9. The immunogenic composition of claim 1 , wherein the immunogenic composition does not yield a reduced immune response to serotype III as compared to a monovalent immunogenic composition comprising a conjugate consisting of serotype III.
10. An immunogenic composition comprising polysaccharide-protein conjugates, wherein
(i) each of the conjugates comprise a capsular polysaccharide from a different serotype of group B Streptococcus (GBS) conjugated to CRM 197 , wherein the serotypes comprise serotypes Ia, Ib, II, III, IV, and V, wherein each capsular polysaccharide has a sialic acid level of greater than 60 percent, and
(ii) the immunogenic composition further comprises one or more of a pharmaceutically acceptable excipient, buffer, stabilizer, adjuvant, a cryoprotectant, a salt, a divalent cation, a non-ionic detergent, an inhibitor of free radical oxidation, a carrier, or a mixture thereof; and
wherein the immunogenic composition comprises 10 mcg/mL to 60 mcg/mL of each conjugate.
11. The immunogenic composition of claim 10 , wherein the immunogenic composition comprises 10 mcg/mL to 40 mcg/mL of each conjugate.
12. The immunogenic composition of claim 10 , wherein the immunogenic composition comprises 10 mcg/mL to 20 mcg/mL of each conjugate.
13. The immunogenic composition of claim 10 , wherein the immunogenic composition comprises 20 mcg/mL to 40 mcg/mL of each conjugate.
14. The immunogenic composition of claim 10 , wherein the immunogenic composition comprises 40 mcg/mL of each conjugate.
15. The immunogenic composition of claim 10 , wherein the buffer is selected from the group consisting of HEPES, PIPES, MES, Tris (trimethamine), phosphate, acetate, borate, citrate, glycine, histidine and succinate.
16. The immunogenic composition of claim 10 , wherein the excipient is selected from the group consisting of starch, glucose, lactose, sucrose, trehalose, raffinose, stachyose, melezitose, dextran, mannitol, lactitol, palatinit, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, glycine, arginine, lysine, sodium chloride (NaCl), dried skim milk, glycerol, propylene glycol, water, and ethanol.
17. The immunogenic composition of claim 10 , further comprising a surfactant is-selected from the group consisting of polyoxyethylene sorbitan fatty acid esters, polysorbate-80, polysorbate-60, polysorbate-40, polysorbate-20, and polyoxyethylene alkyl ethers.
18. The immunogenic composition of claim 10 , wherein the immunogenic composition does not yield a reduced immune response to serotype Ill as compared to a monovalent immunogenic composition comprising a conjugate consisting of serotype Ill.
19. The immunogenic composition of claim 6 , wherein the buffer is histidine.
20. The immunogenic composition of claim 7 , wherein the excipient is sodium chloride.
21. The immunogenic composition of claim 8 , wherein the surfactant is polysorbate-80.
22. The immunogenic composition of claim 1 , wherein the composition is buffered to a pH of 6.0 to 7.0.
23. The immunogenic composition of claim 22 , wherein the composition is buffered to a pH of 6.5.
24. The immunogenic composition of claim 1 , wherein the composition is filled in a syringe.
25. The immunogenic composition of claim 1 , wherein the composition is lyophilized.
26. The immunogenic composition of claim 1 , wherein the composition is for administration via an intramuscular, intraperitoneal, intradermal or subcutaneous injection.
27. The immunogenic composition of claim 15 , wherein the buffer is histidine.
28. The immunogenic composition of claim 16 , wherein the excipient is sodium chloride.
29. The immunogenic composition of claim 17 , wherein the surfactant is polysorbate-80.
30. The immunogenic composition of claim 10 , wherein the composition is buffered to a pH of 6.0 to 7.0.
31. The immunogenic composition of claim 30 , wherein the composition is buffered to a pH of 6.5.
32. The immunogenic composition of claim 10 , wherein the composition is filled in a syringe.
33. The immunogenic composition of claim 10 , wherein the composition is lyophilized.
34. The immunogenic composition of claim 10 , wherein the composition is for administration via an intramuscular, intraperitoneal, intradermal or subcutaneous injection.
35. An immunogenic composition comprising polysaccharide-protein conjugates, wherein
(i) each of the conjugates comprise a capsular polysaccharide from a different serotype of group B Streptococcus (GBS) conjugated to CRM 197 , wherein the serotypes comprise serotypes Ia, Ib, II, III, IV, and V, wherein each capsular polysaccharide has a sialic acid level of greater than 60 percent, and
(ii) the immunogenic composition further comprises histidine, sodium chloride and polysorbate-80; and
wherein the immunogenic composition comprises 40 mcg/mL of each conjugate.
36. The immunogenic composition of claim 35 , wherein the immunogenic composition comprises a total conjugate dose of 240 mcg/mL.
37. The immunogenic composition of claim 35 , wherein the composition comprises 10 mM to 25 mM of histidine, 10 mM to 250 mM of sodium chloride and 0.01% to 0.03% (v/w) of polysorbate-80.
38. The immunogenic composition of claim 37 , wherein the composition comprises 20 mM of histidine, 150 mM of sodium chloride and 0.02% (v/w) of polysorbate-80.