Pharmaceutical compositions containing
This invention relates to compositions including Clostridium difficile toxins and/or toxoids and corresponding methods. The compositions of the invention include one or more excipients that increase stability and/or decrease aggregation of the toxins.
1. A method for inducing an immune response to Clostridium difficile in a subject, the method comprising administering to the subject a composition comprising:
(a) a toxoid of Clostridium difficile toxin A and/or B; and
(b) a sugar or sugar alcohol selected from sucrose, sorbitol, dextrose, and trehalose at a concentration of 1-30%.
2. The method of claim 1 , wherein the sugar or sugar alcohol is selected from sucrose, sorbitol, and trehalose at a concentration of 1-30%.
3. The method of claim 1 , wherein the composition comprises a toxoid of Clostridium difficile toxins A and B.
4. The method of claim 3 , wherein the C. difficile toxoids A and B are present in the composition in a ratio of 5:1 (A:B) to 1:5 (A:B), or are present in the composition in a ratio of 3:1 to 3:2, or 1:1 (A:B).
5. The method of claim 1 , wherein the sugar or sugar alcohol is at a concentration of 5-10%.
6. The method of claim 1 , wherein the composition further comprises a buffer selected from a citrate, phosphate, glycine, histidine, carbonate, bicarbonate, and 4-(2-hydroxyethyl)-1-piperazineethanesulfonic add (HEPES) buffer at a concentration of 5-100 mM.
7. The method of claim 6 , wherein the buffer is a citrate buffer or a phosphate buffer at a concentration of 5-100 mM.
8. The method of claim 6 , wherein the buffer is sodium citrate or potassium citrate.
9. The method of claim 6 , wherein the buffer is sodium phosphate or potassium phosphate.
10. The method of claim 6 , wherein the buffer is at a concentration of 10-30 mM.
11. The method of claim 1 , wherein the buffer is at a concentration of 10-30 mM.
12. The method of claim 1 , wherein the composition further comprises formaldehyde.
13. The method of claim 1 , wherein the pH of the composition is 5.5-8.0.
14. The method of claim 13 , wherein the pH of the composition is 6.5-8.0.
15. The method of claim 1 , wherein the composition is a pharmaceutical composition.
16. The method of claim 1 , wherein the composition further comprises an adjuvant.
17. The method of claim 16 , wherein the adjuvant comprises an aluminum compound.
18. The method of claim 17 , wherein the aluminum compound is an aluminum hydroxide compound.
19. The method of claim 1 , wherein the composition is in liquid form.
20. The method of claim 19 , further comprising reconstituting a dried composition to form said composition in liquid form.
21. The method of claim 6 , wherein the buffer and/or the sugar or sugar alcohol of the composition increases thermal stability of the toxoid and/or reduces aggregation of the toxoid, relative to a composition lacking the buffer and/or sugar or sugar alcohol.
22. A method for inducing an immune response to Clostridium difficile in a subject, the method comprising administering to the subject a composition comprising:
(a) a toxoid of Clostridium difficile toxin A and/or B;
(b) sodium or potassium citrate (5-100 mM);
(c) sucrose (2-20%); and
(d) formaldehyde;
wherein the pH of the composition is 5.5-8.5.
23. The method of claim 22 , wherein the composition comprises sodium or potassium citrate in the amount of 10-30 mM, sucrose in the amount of 2-10%, and formaldehyde in the amount of 0.01-0.018%, wherein the pH of the composition is 6.5-8.0.
24. The method of claim 22 , wherein the composition comprises a toxoid of Clostridium difficile toxin A and toxin B.
25. The method of claim 22 , wherein the composition is in liquid form.
26. A method for inducing an immune response to Clostridium difficile in a subject, the method comprising administering to the subject a composition comprising:
(a) a toxoid of Clostridium difficile toxin A and/or B;
(b) sodium or potassium phosphate (5-100 mM);
(c) sucrose (2-20%); and
(d) formaldehyde;
wherein the pH of the composition is 5.5-8.5.
27. The method of claim 26 , wherein the composition comprises sodium or potassium phosphate in the amount of 10-30 mM, sucrose in the amount of 2-10%, and formaldehyde in the amount of 0.01-0.018%, wherein the pH of the composition is 6.5-8.0.
28. The method of claim 26 , wherein the composition comprises a toxoid of Clostridium difficile toxin A and toxin B.
29. The method of claim 26 , wherein the composition is in liquid form.
30. The method of claim 29 , further comprising reconstituting a dried composition to form said composition in liquid form.
31. The method of claim 1 , wherein the patient does not have, but is at risk of developing, C. difficile disease.
32. The method of claim 1 , wherein the patient has C. difficile disease.