Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof

• US 9,492,559 B2
• Filed: 01/15/2015
• Issued: 11/15/2016
• Est. Priority Date: 01/21/2014
• Status: Active Grant

• Current Assignee: Pfizer Inc.
• Original Assignee: Pfizer Inc.
• Inventors: Emini, Emilio Anthony, Watson, Wendy Jo, Prasad, Avvari Krishna, Han, Mingming, Kim, Jin-Hwan, Gu, Jianxin, Yang, Yu-ying, Kainthan, Rajesh Kumar, Cooper, David, Pride, Michael William, Jansen, Kathrin Ute
• Primary Examiner(s): NAVARRO, ALBERT MARK
• Application Number:
  US14/597,488
• Publication Number:
  US 20150202309A1
• Time in Patent Office: 670 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/6037 Bacterial toxins, e.g. diphteria toxoid [DT], tetanus toxoid [TT]
• CPC Class Codes: A61K 2039/70 Multivalent vaccine
• CPC Class Codes: A61K 39/092 Streptococcus
• CPC Class Codes: A61K 47/646 the entire peptide or protein drug conjugate elicits an immune response, e.g. conjugate vaccines
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention relates to new immunogenic compositions comprising conjugated Streptococcus pneumoniae capsular saccharide antigens (glycoconjugates) and uses thereof. Immunogenic compositions of the present invention will typically comprise at least one glycoconjugate from a S. pneumoniae serotype not found in PREVNAR®, SYNFLORIX® and/or PREVNAR 13®. The invention also relates to vaccination of human subjects, in particular infants and elderly, against pneumoccocal infections using said novel immunogenic compositions.

Claims

1. An immunogenic composition comprising a Streptococcus pneumoniae serotype 22F glycoconjugate, wherein the glycoconjugate has a molecular weight of between 1000 kDa and 12,500 kDa and comprises an isolated capsular polysaccharide from S. pneumoniae serotype 22F and a carrier protein, and wherein a ratio (w/w) of the polysaccharide to the carrier protein is between 0.4 and 2.

2. The immunogenic composition of claim 1, wherein the glycoconjugate comprises at least 0.1 mM acetate per mM polysaccharide.

3. The immunogenic composition of claim 1, wherein the composition further comprises a S. pneumoniae serotype 15B glycoconjugate and a S. pneumoniae serotype 33F glycoconjugate.

4. The immunogenic composition of claim 3, wherein the composition further comprises a S. pneumoniae serotype 12F glycoconjugate, a S. pneumoniae serotype 10A glycoconjugate, a S. pneumoniae serotype 11A glycoconjugate and a S. pneumoniae serotype 8 glycoconjugate.

5. The immunogenic composition of claim 1 further comprising glycoconjugates from S. pneumoniae serotypes 4, 6B, 9V, 14, 18C, 19F and 23F.

6. The immunogenic composition of claim 1 further comprising glycoconjugates from S. pneumoniae serotypes 1, 5 and 7F.

7. The immunogenic composition of claim 1 further comprising glycoconjugates from S. pneumoniae serotypes 6A and 19A.

8. The immunogenic composition of claim 1 further comprising at least one glycoconjugate from S. pneumoniae serotype 3.

9. The immunogenic composition of claim 1, wherein the immunogenic composition is an 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20-valent pneumococcal conjugate composition.

10. The immunogenic composition of claim 1, wherein the carrier protein is selected from the group consisting of DT (Diphtheria toxin), TT (tetanus toxoid), CRM197, other DT mutants, PD (Haemophilus influenzae protein D), and immunologically functional equivalents thereof.

11. The immunogenic composition of claim 1, wherein said immunogenic composition further comprises a buffer, a salt, a divalent cation, a non-ionic detergent, a cryoprotectant, an anti-oxidant, or a combination thereof.

12. The immunogenic composition of claim 11, wherein the composition further comprises a buffer.

13. The immunogenic composition of claim 12, wherein the buffer is phosphate, succinate, histidine or citrate.

14. A syringe filled with the immunogenic composition of claim 1.

15. The syringe of claim 14, wherein the syringe is siliconized or made of glass.

16. The immunogenic composition of claim 10, wherein said carrier protein is CRM₁₉₇.

17. The immunogenic composition of claim 16, wherein said polysaccharide is individually conjugated to CRM₁₉₇.

18. The immunogenic composition of claim 1, wherein each dose of said immunogenic composition comprises 0.1 μ

g to 100 μ

g of the polysaccharide.

19. The immunogenic composition of claim 1, wherein each dose of said immunogenic composition comprises 10 μ

g to 150 μ

g of the carrier protein.

20. The immunogenic composition of claim 1, wherein said immunogenic composition further comprises an antigen from other pathogens.

21. The immunogenic composition of claim 20, wherein said antigen is selected from the group consisting of a diphtheria toxoid (D), a tetanus toxoid (T), a pertussis antigen (P), an acellular pertussis antigen (Pa), a hepatitis B virus (HBV) surface antigen (HBsAg), a hepatitis A virus (HAV) antigen, a conjugated Haemophilus influenzae type b capsular saccharide (Hib), and an inactivated poliovirus vaccine (IPV) antigen.

22. The immunogenic composition of claim 1, wherein said immunogenic composition further comprises a conjugated N. meningitidis serogroup A capsular saccharide (MenA), a conjugated N. meningitidis serogroup W135 capsular saccharide (MenW135), a conjugated N. meningitidis serogroup Y capsular saccharide (MenY), or a conjugated N. meningitidis serogroup C capsular saccharide (MenC).

23. The immunogenic composition of claim 1, wherein said immunogenic composition further comprise at least one adjuvant.

24. The immunogenic composition of claim 23, wherein said at least one adjuvant is selected from the group consisting of aluminum, calcium phosphate, a liposome, an oil-in-water emulsion, and poly(D,L-lactide-co-glycolide) (PLG) microparticles or nanoparticles.

25. The immunogenic composition of claim 24, wherein said adjuvant is an aluminum adjuvant selected from the group consisting of aluminum phosphate, aluminum sulfate and aluminum hydroxide.

26. The immunogenic composition of claim 23, wherein said at least one adjuvant is a CpG Oligonucleotide.

27. The immunogenic composition of claim 1, wherein said immunogenic composition is formulated in liquid form.

28. The immunogenic composition of claim 1, wherein said immunogenic composition is formulated in a lyophilized form.

29. A container filled with the immunogenic composition of claim 1.

30. A method of preventing, treating or ameliorating an infection, disease or condition associated with S. pneumoniae in a subject comprising administering to the subject an effective amount of the immunogenic composition of claim 1.

31. A method of preventing an infection caused by S. pneumoniae in a subject comprising administering to the subject an effective amount of the immunogenic composition of claim 1.

32. The method of claim 30, wherein the subject is a human being less than 2 years of age.

33. The method of claim 30, wherein the subject is a human adult 50 years of age or older.

34. The method of claim 30, wherein the subject is an immunocompromised human.

35. The method of claim 30, wherein the immunogenic composition is administered in a single dose schedule.

36. The method of claim 30, wherein the immunogenic composition is administered in a multiple dose schedule.

37. A method of inducing an immune response to S. pneumoniae serotype 22F in a subject comprising the step of administering an effective amount of the immunogenic composition of claim 1.

38. The immunogenic composition of claim 1, wherein at least 30% of the glycoconjugates have a K_d below or equal to 0.3 in a CL-4B column.

39. The immunogenic composition of claim 1, wherein the glycoconjugates comprise less than about 50% of free polysaccharide compared to a total amount of polysaccharide.

40. The immunogenic composition of claim 1, wherein a ratio of mM acetate per mM polysaccharide in the glycoconjugate to mM acetate per mM isolated polysaccharide is at least 0.6.

41. The immunogenic composition of claim 1, wherein said glycoconjugate is prepared using reductive amination.

42. The immunogenic composition of claim 41, wherein said reductive amination comprises:

(a) oxidation of the polysaccharide to form an activated polysaccharide and

(b) reduction of the activated polysaccharide and a carrier protein to form the glycoconjugate.

43. The immunogenic composition of claim 42, wherein the ratio of mM acetate per mM polysaccharide in the glycoconjugate to mM acetate per mM polysaccharide in the activated polysaccharide is at least 0.6.

44. The immunogenic composition of claim 1, wherein the degree of conjugation of said glycoconjugate is between 2 and 15.

45. The immunogenic composition of claim 1, wherein the polysaccharide has a molecular weight of between 10 kDa and 2,000 kDa.