METHODS AND COMPOSITIONS FOR INCREASING PROTECTIVE ANTIBODY LEVELS INDUCED BY PNEUMOCOCCAL POLYSACCHARIDE VACCINES

• US 20160311904A1
• Filed: 12/22/2014
• Published: 10/27/2016
• Est. Priority Date: 12/20/2013
• Status: Active Grant

• Current Assignee: Wake Forest University Health Sciences
• Original Assignee: Wake Forest University Health Sciences
• Inventors: Haas, Karen, Mckay, Jerome
• Granted Patent: US 11,708,411 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/6087 Polysaccharides; Lipopolysaccharides [LPS]
• CPC Class Codes: A61K 2039/70 Multivalent vaccine
• CPC Class Codes: A61K 39/092 Streptococcus
• CPC Class Codes: A61K 39/116 Polyvalent bacterial antigens
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: C07K 16/2827 against B7 molecules, e.g. CD80, CD86
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding

Abstract

The presently disclosed subject matter provides therapeutic methods and compositions for the treatment of bacterial infections caused by Streptococcus pneumoniae. In particular, methods are provided for increasing protective antibody levels induced by pneumococcal polysaccharide vaccines in a subject in need thereof comprising administering to the subject an effective amount of an agent that inhibits the interaction between a PD-1 ligand and a PD-1 polypeptide. Immunogenic compositions are also provided comprising one or more pneumococcal polysaccharide antigens and an agent that inhibits the interaction between a PD-1 ligand and a PD-1 polypeptide.

Claims

1. A method for increasing protective antibody levels induced by one or more pneumococcal polysaccharide antigens in a subject in need thereof, the method comprising administering to the subject an effective amount of an agent that inhibits the interaction between a PD-1 ligand and a PD-1 polypeptide.

2. The method of claim 1, wherein the one or more pneumococcal polysaccharide antigens are capsular polysaccharides from one or more different serotypes of Streptococcus pneumoniae.

3. The method of claim 2, wherein the one or more different serotypes of Streptococcus pneumoniae are selected from the group consisting of serotypes 1, 2, 3, 4, 5, 6A, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F.

4. The method of claim 1, wherein the PD-1 polypeptide comprises the amino acid sequence of SEQ ID NO:

1 or a functional variant thereof comprising an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO;

1.

5. The method of claim 4, wherein the PD-1 ligand is PDL1 and comprises the amino acid sequence of SEQ ID NO:

2 or a functional variant thereof comprising an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO;

2.

6. The method of claim 4, wherein the PD-1 ligand is PDL2 and comprises the amino acid sequence of SEQ ID NO:

3 or a functional variant thereof comprising an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO;

3.

7. The method of claim 1, wherein the agent is selected from the group consisting of an anti-PD-1 ligand antibody, a small molecule, a peptide, and a fusion protein.

8. The method of claim 1, wherein the one or more pneumococcal polysaccharide antigens and the agent that inhibits the interaction between a PD-1 ligand and a PD-1 polypeptide are administered simultaneously to the subject.

9. The method of claim 1, wherein the one or more pneumococcal polysaccharide antigens and the agent that inhibits the interaction between a PD-1 ligand and a PD-1 polypeptide are administered sequentially to the subject.

10. A method of treating a bacterial infection caused by Streptococcus pneumoniae in a subject in need thereof, the method comprising increasing protective antibody levels induced by one or more pneumococcal polysaccharide antigens in the subject, wherein protective antibody levels are increased by administering to the subject an effective amount of an agent that inhibits the interaction between a PD-1 ligand and a PD-1 polypeptide.

11. The method of claim 10, wherein the bacterial infection caused by Streptococcus pneumoniae is selected from the group consisting of pneumonia, acute sinusitis, otitis media, meningitis, bacteremia, sepsis, osteomyelitis, septic arthritis, endocarditis, peritonitis, pericarditis, cellulitis, and brain abscess.

12. The method of claim 10, wherein the subject is 2 years old or younger.

13. The method of claim 12, wherein the bacterial infection caused by Streptococcus pneumoniae is otitis media.

14. The method of claim 10, wherein the subject is 50 years old or older and/or is immunocompromised.

15. The method of claim 14, wherein the bacterial infection caused by Streptococcus pneumoniae is pneumonia.

16. The method of claim 10, wherein the one or more pneumococcal polysaccharide antigens are capsular polysaccharides from one or more different serotypes of Streptococcus pneumoniae.

17. The method of claim 16, wherein the one or more different serotypes of Streptococcus pneumoniae are selected from the group consisting of serotypes 1, 2, 3, 4, 5, 6A, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F.

18. The method of claim 10, wherein the PD-1 polypeptide comprises the amino acid sequence of SEQ ID NO:

1 or a functional variant thereof comprising an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO;

1.

19. The method of claim 18, wherein the PD-1 ligand is PDL1 and comprises the amino acid sequence of SEQ ID NO:

2 or a functional variant thereof comprising an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO;

2

20. The method of claim 18, wherein the PD-1 ligand is PDL2 and comprises the amino acid sequence of SEQ ID NO:

3 or a functional variant thereof comprising an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO;

3.

21. The method of claim 10, wherein the agent is selected from the group consisting of an anti-PD-1 ligand antibody, a small molecule, a peptide, and a fusion protein.

22. The method of claim 10, wherein the one or more pneumococcal polysaccharide antigens and the agent that inhibits the interaction between a PD-1 ligand and a PD-1 polypeptide are administered simultaneously to the subject.

23. The method of claim 10, wherein the one or more pneumococcal polysaccharide antigens and the agent that inhibits the interaction between a PD-1 ligand and a PD-1 polypeptide are administered sequentially to the subject.

24. An immunogenic composition comprising:

a) one or more pneumococcal polysaccharide antigens;

b) an effective amount of an agent that inhibits the interaction between a PD-1 ligand and a PD-1 polypeptide; and

c) a pharmaceutically acceptable carrier.

25. The immunogenic composition of claim 24, wherein the one or more pneumococcal polysaccharide antigens are capsular polysaccharides from one or more different serotypes of Streptococcus pneumoniae.

26. The immunogenic composition of claim 25, wherein the one or more different serotypes of Streptococcus pneumoniae are selected from the group consisting of serotypes 1, 2, 3, 4, 5, 6A, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F.

27. The immunogenic composition of claim 24, wherein the PD-1 polypeptide comprises the amino acid sequence of SEQ ID NO:

1 or a functional variant thereof comprising an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO;

1.

28. The immunogenic composition of claim 27, wherein the PD-1 ligand is PDL1 and comprises the amino acid sequence of SEQ ID NO:

2 or a functional variant thereof comprising an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO;

2.

29. The immunogenic composition of claim 27, wherein the PD-1 ligand is PDL2 and comprises the amino acid sequence of SEQ ID NO:

3 or a functional variant thereof comprising an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO;

3.

30. The immunogenic composition of claim 24, wherein the agent is selected from the group consisting of an anti-PD-1 ligand antibody, a small molecule, a peptide, and a fusion protein.

31. The immunogenic composition of claim 24, wherein the one or more pneumococcal polysaccharide antigens are conjugated to a carrier protein.

32. The immunogenic composition of claim 24, further comprising an adjuvant.

33. A kit for increasing protective antibody levels induced by one or more pneumococcal polysaccharide antigens in a subject in need thereof, the kit comprising:

a) a pneumococcal polysaccharide vaccine comprising one or more pneumococcal polysaccharide antigens;

b) an agent that inhibits the interaction between a PD-1 ligand and a PD-1 polypeptide; and

c) instructions for administration of the pneumococcal polysaccharide vaccine and the agent to the subject.

34. A kit for treating a bacterial infection caused by Streptococcus pneumoniae in a subject in need thereof, the kit comprising:

a) a pneumococcal polysaccharide vaccine comprising one or more pneumococcal polysaccharide antigens;

b) an agent that inhibits the interaction between a PD-1 ligand and a PD-1 polypeptide; and

c) instructions for administration of the pneumococcal polysaccharide vaccine and the agent to the subject.