Candida albicans phosphomannan complex as a vaccine

• US 6,630,146 B2
• Filed: 12/11/2000
• Issued: 10/07/2003
• Est. Priority Date: 05/23/1994
• Status: Expired due to Fees

• Current Assignee: Takeda Vaccines Montana Incorporated (Takeda Pharmaceutical Company Limited)
• Original Assignee: Montana State University
• Inventors: Cutler, Jim E., Han, Yongmoon
• Primary Examiner(s): Allen, Marianne P.
• Assistant Examiner(s): Clow, Lori A.
• Application Number:
  US09/733,066
• Publication Number:
  US 20020054886A1
• Time in Patent Office: 1,030 Days
• Field of Search: 424/184.1, 424/274.1, 424/278.1, 424/9.2, 424/9.34, 530/371
• US Class Current: 424/184.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 39/0002 Fungal antigens, e.g. Trichophyton, Aspergillus, Candida
• CPC Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: A61K 9/1271 Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers liposome as conjugate A61K47/6911
• CPC Class Codes: C07K 14/40 from Candida
• CPC Class Codes: C07K 16/14 against material from fungi, algea or lichens
• CPC Class Codes: C07K 7/06 having 5 to 11 amino acids

Abstract

A composition, pharmaceutical composition, vaccine and method for the treatment of disseminated candidiasis due to infection by C. albicans. The composition includes phosphomannan of C. albicans. Monoclonal antibodies for use in passive immunization against candidal infections.

Claims

1. A vaccine against candidiasis, comprising a solubilized adhesin extract of the phosphomannoprotein complex of the cell surface of an organism from the genus Candida, said adhesin extract being complexed or conjugated to a pharmaceutically acceptable carrier so as to elicit a protective immune response.

2. The vaccine of claim 1, wherein said candidiasis is selected from the group consisting of hematogenous disseminated candidiasis and mucocutaneous candidiasis.

3. The vaccine of claim 1, wherein said Candida is selected from the group consisting of Candida albicans serotypes A and B, and Candida tropicalis.

4. The vaccine of claim 1, wherein said organism has been grown at 37°

C.

5. The vaccine of claim 1, wherein said organism is in a stationary phase of growth.

6. The vaccine of claim 1, wherein said phosphomannoprotein complex is solubilized by β

-mercaptoethanol.

7. The vaccine of claim 1, wherein said extract comprises oligomannosyl chains.

8. The vaccine of claim 7, wherein said oligomannosyl chains are selected from the group consisting of the acid labile and acid stable portions of the phosphomannoprotein complex.

9. The vaccine of claim 8, wherein said oligomannosyl chains are selected from the group consisting of α

-1,6-linked, α

-1,3-linked, α

-1,2-linked and β

-1,2-linked oligomannosyl structures that have single or combinations of linkage types as found in the phosphomannoprotein complex.

10. The vaccine of claim 9, wherein the number of mannose units in said β

-1,2-linked oligomannosyl chains ranges from one to seven.

11. The vaccine of claim 10, wherein said β

-1,2-linked oligomannosyl chains are β

-1,2-linked tri-mannosyl residues.

12. The vaccine of claim 7, wherein said oligomannosyl chains are complexed or conjugated to said carrier.

13. The vaccine of claim 1, wherein said adhesin extract is present in an amount from about 0.1 μ

g to 500 mg per human dose.

14. The vaccine of claim 1, wherein said carrier is selected from the group consisting of proteins, polysaccharides, liposomes and vectors.

15. The vaccine of claim 1, wherein said vaccine comprises about 0.01 to 99.0% by weight of said adhesin extract.

16. The vaccine of claim 1, wherein said vaccine comprises about 0.5 gram of said adhesin extract per each 150 pounds of a human patient.

17. The vaccine of claim 1, formulated for oral, subcutaneous or intramuscular administration.

18. The vaccine of claim 1, wherein said phosphomannoprotein specifically binds to MAb B6.1.

19. The vaccine of claim 1, wherein said solubilized adhesin extract consists essentially of trimannosyl chains.

20. A method for immunization of a patient against candidiasis, comprising administering to a patient in need of said immunization a vaccine according to any one of claims 1-19.

21. A vaccine against candidiasis consisting essentially of oligomannosyl chains complexed or conjugated to a pharmaceutically acceptable carrier.

22. The vaccine of claim 21, wherein said oligomannosyl chains are selected from the group consisting of acid stable oligomannosyl chains, acid labile oligomannosyl chains or both.

23. The vaccine of claim 21, wherein said oligomannosyl chains include one or more oligomannosyl chains having linkages selected from the group consisting of α

-1,6-linkages, α

-1,3-linkages, α

-1,2-linkages and β

-1,2-linkages and combinations thereof.

24. The vaccine of claim 23, wherein said β

-1,2-linked oligomannosyl chains contain a number of mannose units ranging from one to seven.

25. The vaccine of claim 24, wherein said β

-1,2-linked oligomannosyl chains include β

-1,2-linked trimannosyl chains.

26. The vaccine of claim 21, wherein said oligomannosyl chains are complexed or conjugated to said carrier so as to elicit a humoral immune response.

27. The vaccine of claim 21, wherein said carrier is selected from the group consisting of proteins, polysaccharides, liposomes and vectors.

28. The vaccine of claim 21, wherein said candidiasis is selected from the group consisting of hematogenous disseminated candidiasis and mucocutaneous candidiasis.

29. The vaccine of claim 21, formulated for oral, subcutaneous or intramuscular administration.

30. The vaccine of claim 21, wherein said oligomannosyl chains are present in an amount from about 0.1 μ

g to 500 mg per human dose.

31. The vaccine of claim 21, wherein said vaccine comprises about 0.01 to 99.0% by weight of said oligomannosyl chains.

32. The vaccine of claim 21, wherein said vaccine comprises about 0.5 gram of said oligomannosyl chains per each 150 pounds of a human patient.

33. The vaccine according to claim 21, wherein said oligomannosyl chains specifically bind to MAb B6.1.

35. A method for immunization of a patient against candidiasis, comprising administering to a patient in need of said immunization a vaccine according to any one of claims 21-34.

34. A vaccine against candidiasis consisting essentially of trimannosyl chains complexed or conjugated to a pharmaceutically acceptable carrier.