Polypeptide comprising the amino acid of an N-terminal choline binding protein a truncate, vaccine derived therefrom and uses thereof

• US 20040120966A1
• Filed: 01/05/2004
• Published: 06/24/2004
• Est. Priority Date: 04/07/1998
• Status: Active Grant

• Current Assignee: St Jude Children's Research Hospital Incorporated (Abbott Laboratories), Medimmune Incorporated (Astrazeneca PLC)
• Original Assignee: St Jude Children's Research Hospital Incorporated (Abbott Laboratories), Medimmune Incorporated (Astrazeneca PLC)
• Inventors: Johnson, Leslie Sydnor, Koenig, Scott, Tuomanen, Elaine I., Wizemann, Theresa M., Masure, H. Robert
• Granted Patent: US 7,479,282 B2
• Time in Patent Office: Days
• US Class Current: 424/184.1
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: C07K 14/3156 from Streptococcus pneumoniae (Pneumococcus) Streptokinase C07K14/3153

Abstract

This invention provides an isolated polypeptide comprising an amino acid sequence of a N-terminal choline binding protein A truncate in which the amino acid sequence is set forth in any of SEQ ID NOS: 1, 3-7, or 9-11, including fragments, mutants, variants, analogs, or derivatives, thereof. Also, this invention provides a isolated polypeptide comprising an amino acid sequence of a N-terminal choline binding protein A truncate, wherein the amino acid is set forth in SEQ ID NO: 24, wherein the polypeptide retains its native tertiary structure and methods of preparation. This invention provides an isolated polypeptide comprising an amino acid sequence of a N-terminal choline binding protein A truncate, wherein the polypeptide has lectin activity and does not bind to choline. This invention provides an isolated immunogenic polypeptide comprising an amino acid sequence of a N-terminal choline binding protein A truncate. This invention provides an isolated nucleic acid encoding a polypeptide comprising an amino acid sequence of a N-terminal choline binding protein A truncate. Lastly, this invention provides pharmaceutical compositions, vaccines, and diagnostic and therapeutic methods of use.

Claims

1. A vaccine for treating or protecting against pneumococcal infection comprising a polypeptide in a pharmaceutically acceptable carrier wherein said polypeptide comprises a variant of SEQ ID NO:

4, said variant comprises at least one to 15 amino acid substitutions and comprises amino acids 331 to 339, 355 to 365, 367 to 374, 379 to 389 and 409 to 427 of SEQ ID NO;

40, said polypeptide does not bind to choline, said polypeptide exhibits a tertiary structure as found in a native, full-length CbpA polypeptide, and the polypeptide content of said vaccine being in an amount effective for treating or protecting against pneumococcal infection.

2. The vaccine of claim 1, wherein said polypeptide interacts with an antibody, said antibody is capable of interacting with domain C of the full-length CbpA polypeptide.

3. The vaccine of claim 1, wherein said polypeptide comprises a C domain identical to a polypeptide that is a competitive inhibitor of bacterial adhesion of pneumococcal.

4. The vaccine of claim 1, wherein said amino acid sequence is identical to the amino acid sequence of an N-terminal choline binding protein.

5. The vaccine of claim 1, wherein said vaccine when administered elicits an antibody that protects against pneumococcal infection in a mammal.

6. The vaccine of claim 5 wherein said mammal is a human.

7. The vaccine of claim 1 wherein said vaccine further comprises an adjuvant.

8. The vaccine of claim 1, wherein said variant of SEQ ID NO:

4 comprises amino acids 331 to 339, 355 to 365, 367 to 374, 379 to 389 and 409 to 427 of SEQ ID NO;

40.

9. The vaccine of claim 8, wherein said polypeptide interacts with an antibody, said antibody is capable of interacting with domain C of a full-length CbpA polypeptide

10. The vaccine of claim 8, wherein said polypeptide comprises a C domain identical to a polypeptide that is a competitive inhibitor of bacterial adhesion of pneumococcal.

11. The vaccine of claim 8, wherein said amino acid sequence is identical to the amino acid sequence of an N-terminal choline binding protein.

12. The vaccine of claim 8, wherein said vaccine when administered elicits an antibody that protects against pneumococcal infection in a mammal.

13. The vaccine of claim 12 wherein said mammal is a human.

14. The vaccine of claim 8 wherein said vaccine further comprises an adjuvant.

15. The vaccine of claim 1, wherein said polypeptide comprises SEQ ID NO:

4.

16. A vaccine for treating or protecting against pneumococcal infection comprising a polypeptide in a pharmaceutically acceptable carrier wherein said polypeptide comprises a variant of SEQ ID NO:

40, said variant comprises at least one to 15 amino acid substitutions and comprises amino acids 331 to 339, 355 to 365, 367 to 374, 379 to 389 and 409 to 427 of SEQ ID NO;

40, said polypeptide does not bind to choline, said polypeptide exhibits a tertiary structure of a native, full-length CbpA polypeptide, and the polypeptide content of said vaccine being in an amount effective for treating or protecting against pneumococcal infection.

17. The vaccine of claim 16, wherein said polypeptide interacts with an antibody, said antibody is capable of interacting with domain C of the full-length CbpA polypeptide.

18. The vaccine of claim 16, wherein said polypeptide comprises a C domain identical a to polypeptide that is a competitive inhibitor of bacterial adhesion of pneumococcal.

19. The vaccine of claim 16, wherein said amino acid sequence is identical to the amino acid sequence of an N-terminal choline binding protein.

20. The vaccine of claim 16, wherein said vaccine when administered elicits an antibody that protects against pneumococcal infection in a mammal.

21. The vaccine of claim 20, wherein said mammal is a human.

22. The vaccine of claim 16, wherein said vaccine further comprises an adjuvant.

23. The vaccine of claim 16, wherein said polypeptide comprises amino acids 327 to 433 of SEQ ID NO:

40.

24. The vaccine of claim 16, wherein said variant of SEQ ID NO:

40 comprises amino acids 331 to 339, 355 to 365, 367 to 374, 379 to 389 and 409 to 427 of SEQ ID NO;

40.

25. The vaccine of claim 24, wherein said polypeptide interacts with an antibody, said antibody is capable of interacting with domain C of the full-length CbpA polypeptide

26. The vaccine of claim 24, wherein said polypeptide comprises a C domain identical to a polypeptide that is a competitive inhibitor of bacterial adhesion of pneumococcal.

27. The vaccine of claim 24, wherein said amino acid sequence is identical to the amino acid sequence of an N-terminal choline binding protein.

28. The vaccine of claim 24, wherein said vaccine when administered elicits an antibody that protects against pneumococcal infection in a mammal.

29. The vaccine of claim 28, wherein said mammal is a human.

30. The vaccine of claim 24, wherein said vaccine further comprises an adjuvant.

31. A vaccine for treating or protecting against pneumococcal infection comprising a polypeptide in a pharmaceutically acceptable carrier wherein said polypeptide comprises a variant of SEQ ID NO:

40 comprising about amino acids 327 to amino acid 433 of SEQ ID NO;

40, said variant comprising at least one to 15 amino acid substitutions, said polypeptide does not bind to choline, said polypeptide exhibits a tertiary structure as found in a native, full-length CbpA polypeptide, and the polypeptide content of said vaccine being in an amount effective for treating or protecting against pneumococcal infection.

32. The vaccine of claim 31, wherein said polypeptide interacts with an antibody, said antibody is capable of interacting with domain C of the full-length CbpA polypeptide.

33. The vaccine of claim 31, wherein said polypeptide comprises a C domain identical to a polypeptide that is a competitive inhibitor of bacterial adhesion of pneumococcal.

34. The vaccine of claim 31, wherein said amino acid sequence is identical to the amino acid sequence of an N-terminal choline binding protein.

35. The vaccine of claim 31, wherein said vaccine when administered elicits an antibody that protects against pneumococcal infection in a mammal.

36. The vaccine of claim 35 wherein said mammal is a human.

37. The vaccine of claim 31 wherein said vaccine further comprises an adjuvant.