Gamma-glutamyl transpeptidase attenuated Francisella

• US 8,609,108 B2
• Filed: 04/14/2010
• Issued: 12/17/2013
• Est. Priority Date: 04/14/2009
• Status: Expired due to Fees

• Current Assignee: Secretary of State For Defence
• Original Assignee: Secretary of State For Defence
• Inventors: Le Butt, Helen, Ireland, Phillip Matthew, Oyston, Petra Claire Farquar
• Primary Examiner(s): Devi, S.
• Application Number:
  US13/264,175
• Publication Number:
  US 20120107360A1
• Time in Patent Office: 1,343 Days
• Field of Search: None
• US Class Current: 424/200.1
• 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: A61P 37/04 Immunostimulants

Abstract

The present invention relates to a mutated Francisella bacterium, wherein the ggt gene is silenced or deleted; pharmaceutical compositions comprising the same, in particular, vaccine compositions, and use of the bacterium and compositions for treatment and/or prophylaxis, and in particular, the treatment or prophylaxis of tularemia.

Claims

1. An attenuated Francisella mutant bacterium, wherein the gene gamma-glutamyl transpeptidase (ggt) is deleted.

2. The attenuated Francisella mutant bacterium of claim 1, wherein the attenuated Francisella mutant bacterium is attenuated Francisella tularensis.

3. The attenuated Francisella mutant bacterium of claim 1, wherein the attenuated Francisella mutant bacterium is attenuated Francisella tularensis.

4. The attenuated Francisella mutant bacterium of claim 1, wherein the attenuated Francisella mutant bacterium is derived from SCHU S4 strain of Francisella tularensis tularensis.

5. The attenuated Francisella mutant bacterium of claim 1, wherein a further gene of the bacterium is deleted or silenced.

6. The attenuated Francisella mutant bacterium of claim 5, wherein the silenced or the deleted further gene is the ferrous iron transport protein B (feoB) gene.

7. A pharmaceutical composition comprising the attenuated Francisella mutant bacterium of claim 4 and a pharmaceutically acceptable carrier.

8. The pharmaceutical composition of claim 7, wherein the pharmaceutical composition is a vaccine composition.

9. A method of preparing the attenuated Francisella mutant bacterium of claim 1, comprising deleting the ggt gene in a wild-type Francisella bacterium.

10. The method of claim 9, further comprising deleting or silencing a further gene of the bacterium.

11. The attenuated Francisella mutant bacterium obtained by the method of claim 1.

16. The attenuated Francisella mutant bacterium of claim 1, wherein the attenuated Francisella mutant bacterium is 1,000,000 or more times less virulent than the corresponding wild-type Francisella bacterium.

17. The attenuated Francisella mutant bacterium of claim 6, wherein the attenuated Francisella mutant bacterium is 1,000,000 or more times less virulent than the corresponding wild-type Francisella bacterium.

18. A composition comprising the attenuated Francisella mutant bacterium of claim 1 and a pharmaceutically acceptable carrier.

12. A method of formulating a composition comprising an attenuated Francisella mutant having at least the deleted ggt gene, the method comprising:

culturing the attenuated Francisella mutant having at least the deleted ggt gene and

admixing the cultured attenuated Francisella mutant with a pharmaceutically acceptable excipient.

13. The method of claim 12, wherein the culturing is performed in a culture medium and at a temperature suitable for growth of the attenuated Francisella mutant.

14. The method of claim 13, wherein the culture medium is blood cysteine glucose agar (BCGA).

15. The method of claim 14, wherein the temperature is about 37°

C.