LIVE VACCINE STRAINS OF FRANCISELLA

• US 20100021501A1
• Filed: 07/25/2007
• Published: 01/28/2010
• Est. Priority Date: 07/25/2006
• Status: Active Grant

• Current Assignee: Secretary of State For Defence
• Original Assignee: Secretary of State For Defence
• Inventors: Titball, Richard William, Oyston, Petra Claire Farguhar, Mitchell, Stephen Lloyd
• Granted Patent: US 8,323,664 B2
• Time in Patent Office: Days
• US Class Current: 424/234.100
• CPC Class Codes: A61K 2039/522 avirulent or attenuated
• CPC Class Codes: A61K 39/0208 Specific bacteria not otherwise provided for
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: C12N 1/36 Adaptation or attenuation of cells
• CPC Class Codes: C12N 15/52 Genes encoding for enzymes or proenzymes
• CPC Class Codes: C12N 15/74 Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora
• 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

A strain of Francisella species wherein a gene which encodes for part of the glutamate metabolic pathway has been inactivated, and which is able to produce a protective immune response in an animal, for use as live prophylactic or therapeutic vaccine against infection by said Francisella species. Particularly effective strains include those where the capB gene is deleted. Other embodiments of the invention describe strains which comprise a further genetic mutation wherein a gene which encodes for another component of the cell is also inactivated. Pharmaceutical compositions comprising said strains, together with methods which utilise such strains are also described and claimed.

Claims

1. A strain of Francisella species wherein a gene which encodes for part of the glutamate metabolic pathway has been inactivated, and which is able to produce a protective immune response in an animal, for use as live prophylactic or therapeutic vaccine against infection by said Francisella species.

2. The strain of claim 1 wherein the gene encodes for the synthesis of capsule

3. The strain of claim 1 wherein the gene is selected from the group of genes consisting of FTT0808, capB, and capC.

4. The strain of claim 3 wherein the gene is capB.

5. The strain of claim 3 wherein the gene is capC.

6. The strain of claim 1 wherein said gene is inactivated by complete or partial deletion mutation or by insertional mutation.

7. The strain of claim 1 which is a strain of Francisella tularensis.

8. The strain of claim 7 which is a strain of Francisella tularensis subspecies tularensis.

9. The strain of claim 7 which is a strain of Francisella tularensis subspecies holarctica.

10. The strain of claim 7 which is Francisella tularensis subspecies tularensis SchuS4

11. The strain of claim 1 which comprises a further genetic mutation wherein a gene which encodes for another component of the cell is also inactivated.

12. The strain of claim 11 wherein the gene which encodes for another component of the cell is selected from the group consisting of FTT0918, FTT0919 and FTT1564.

13. The strain of claim 11 wherein the gene which encodes for another component of the cell is a gene which encodes for a pilin subunit or is a gene which encodes for an enzyme in the purine pathway.

14. The strain of claim 13 wherein the gene which encodes for another component of the cell is a gene selected from the group consisting of pilA, pilE, pilC, purA and purF.

15. The strain of claim 11 wherein the gene which encodes for another component of the cell is inactivated by complete or partial deletion mutation or by insertional mutation.

35. A method of preventing or treating infection caused by Francisella species, which method comprises administering to an animal an effective amount of a strain of claim 1.

16. A pharmaceutical composition comprising a live strain of a Francisella species wherein a gene which encodes for part of the glutamate metabolic pathway has been inactivated, and which is able to produce a protective immune response in an animal, in combination with a pharmaceutically acceptable carrier.

17. The pharmaceutical composition of claim 16 wherein the gene is selected from the group of genes consisting of FTT0808, capB, and capC.

18. The pharmaceutical composition of claim 17 wherein the gene is capB.

19. The pharmaceutical composition of claim 17 wherein the gene is capC.

20. The pharmaceutical composition of claim 16 wherein said gene is inactivated by complete or partial deletion mutation or by insertional mutation.

21. The pharmaceutical composition of claim 16 wherein said live strain is a strain of Francisella tularensis.

22. The pharmaceutical composition of claim 21 wherein said strain is a strain of Francisella tularensis subspecies tularensis.

23. The pharmaceutical composition of claim 21 wherein said strain is a strain of Francisella tularensis subspecies holarctica.

24. The pharmaceutical composition of claim 21 wherein said strain is Francisella tularensis subspecies tularensis SchuS4.

36. A method of preventing or treating infection caused by Francisella species, which method comprises administering to an animal an effective amount of a pharmaceutical composition of claim 16.

25-34. -34. (canceled)

37-39. -39. (canceled)