Plague vaccine

Patent metadata

Field	Value
Publication number	US-9492524-B2
Application number	US-201214419925-A
Country	US
Kind code	B2
Filing date	Aug 7, 2012
Priority date	Aug 7, 2012
Publication date	Nov 15, 2016
Grant date	Nov 15, 2016

Abstract

The application relates to a Yersinia pseudotuberculosis cell, which comprises nucleic acid coding for expression of at least one Yersinia pestis Caf1 polypeptide or of at least one antigenic fragment of Yersinia pestis Caf1, more particularly to an attenuated Y. pseudotuberculosis cell, which expresses the Y. pestis capsule. Said Y. pseudotuberculosis cell is exceptionally efficient in protecting against both bubonic plague and pulmonary plague.

First claim

The invention claimed is:

1. A genetically attenuated Yersinia pseudotuberculosis cell, wherein one or more genes selected from HPI, yopK and psaA are deleted or inactivated, and wherein nucleic acid coding for expression of at least one Yersinia pestis Caf1 polypeptide at the surface of said Y. pseudotuberculosis cell is integrated into the chromosome of said Y. pseudotuberculosis cell.

2. The genetically attenuated Y. pseudotuberculosis cell of claim 1 , which is a live cell or a killed cell.

3. The genetically attenuated Y. pseudotuberculosis cell of claim 2 , which expresses said at least one surface-expressed Y. pestis Caf1 in oligomeric form.

4. The genetically attenuated Y. pseudotuberculosis cell of claim 1 , which expresses the Y. pestis F1 protein at its surface.

5. The genetically attenuated Y. pseudotuberculosis cell of claim 1 , which is surrounded by a Y. pestis capsule.

6. The genetically attenuated Yersinia pseudotuberculosis cell of claim 1 , which derives from a cell of the Y. pseudotuberculosis IP 32953 strain, the chromosomal sequence of which is the sequence available under accession number NC_006155 (SEQ ID NO: 19), by:
deletion or inactivation of one or more genes selected from HPI, yopK and psaA, and by
chromosomal insertion of nucleic acid coding for expression of at least one Yersinia pestis Caf1 polypeptide at the surface of said Y. pseudotuberculosis cell.

7. The genetically attenuated Yersinia pseudotuberculosis cell of claim 1 , wherein at least one transposon carrying the caf operon is integrated in the chromosome of said Y. pseudotuberculosis cell.

8. A composition comprising a plurality of genetically attenuated Yersinia pseudotuberculosis cells according to claim 1 .

9. An immunogenic composition, comprising an immunogenically effective amount of live genetically attenuated Yersinia pseudotuberculosis cells;
wherein the HPI gene is deleted or inactivated in the Yersinia pseudotuberculosis cells, the yopK gene is deleted or inactivated in the Yersinia pseudotuberculosis cells, and the psaA gene is deleted or inactivated in the Yersinia pseudotuberculosis cells; and
wherein nucleic acid coding for expression of at least one Yersinia pestis Caf1 polypeptide at the surface of said Y. pseudotuberculosis cell is integrated into the chromosome of said Y. pseudotuberculosis cell.

10. The immunogenic composition of claim 9 , which comprises a single unit dose of the live genetically attenuated Yersinia pseudotuberculosis cells.

11. A method for treating a Y. pestis infection in a mammal, which comprises administering an effective amount of the immunogenic composition of claim 9 to said mammal having a Y. pestis infection to thereby treat the Y. pestis infection in said mammal.

12. The method of claim 11 , wherein said mammal is a human.

13. A method of immunizing a mammal against Y. pestis infection, comprising administering an effective immunizing amount of the immunogenic composition of claim 9 to said mammal.

14. The method of claim 13 , wherein said mammal is a human.

15. A vaccine comprising an immunizing amount of live genetically attenuated Yersinia pseudotuberculosis cells;
wherein the HPI gene is deleted or inactivated in the Yersinia pseudotuberculosis cells, the yopK gene is deleted or inactivated in the Yersinia pseudotuberculosis cells, and the psaA gene is deleted or inactivated in the Yersinia pseudotuberculosis cells; and
wherein nucleic acid coding for expression of at least one Yersinia pestis Caf1 polypeptide at the surface of said Y. pseudotuberculosis cell is integrated into the chromosome of said Y. pseudotuberculosis cell.

16. The vaccine of claim 15 , which comprises a single unit dose of the live genetically attenuated Yersinia pseudotuberculosis cells.

17. The vaccine of claim 15 , which is formulated for oral administration.

18. The vaccine of claim 15 , which is formulated for subcutaneous, intradermal, intranasal, or intramuscular administration.

19. The vaccine of claim 15 , which is formulated for non-oral administration.

Assignees

• Carniel Elisabeth
• Demeure Christian
• Derbise Anne
• Pasteur Institut

Inventors

• Carniel Elisabeth
• Demeure Christian
• Derbise Anne

Classifications

• A61K39/0291 Primary

  Yersinia · CPC title

• A61K2039/523

  expressing foreign proteins · CPC title

• A61K2039/522

  avirulent or attenuated · CPC title

• C12N1/36

  Adaptation or attenuation of cells · CPC title

• A61K2039/542

  oral/gastrointestinal · CPC title